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Sample records for benzyl derivatives evaluated

  1. Electron impact study of molecular ions of some benzyl derivatives

    International Nuclear Information System (INIS)

    Selim, E.T.; Rabia, M.A.; Fahmy, M.A.

    1992-01-01

    The ionization energies at threshold and values of higher energy levels for the molecular ions of benzyl alcohol, benzyl amine and benzyl cyanide are reported using electron impact technique. The first ionization energy values are found to be 8.26 eV (benzyl alcohol), 8.49 eV(benzyl amine)and 9.32 eV (benzyl cyanide). Some of the reported higher energy levels for the molecular ions are tentatively explained. The differences in the relative abundances for the main fragment ions are discussed and attributed to the effect of the different substituents - OH, -NH2 and -CN groups

  2. Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer's disease.

    Science.gov (United States)

    Lan, Jin-Shuai; Hou, Jian-Wei; Liu, Yun; Ding, Yue; Zhang, Yong; Li, Ling; Zhang, Tong

    2017-12-01

    A novel family of cinnamic acid derivatives has been developed to be multifunctional cholinesterase inhibitors against AD by fusing N-benzyl pyridinium moiety and different substituted cinnamic acids. In vitro studies showed that most compounds were endowed with a noteworthy ability to inhibit cholinesterase, self-induced Aβ (1-42) aggregation, and to chelate metal ions. Especially, compound 5l showed potent cholinesterase inhibitory activity (IC 50 , 12.1 nM for eeAChE, 8.6 nM for hAChE, 2.6 μM for eqBuChE and 4.4 μM for hBuChE) and the highest selectivity toward AChE over BuChE. It also showed good inhibition of Aβ (1-42) aggregation (64.7% at 20 μM) and good neuroprotection on PC12 cells against amyloid-induced cell toxicity. Finally, compound 5l could penetrate the BBB, as forecasted by the PAMPA-BBB assay and proved in OF1 mice by ex vivo experiments. Overall, compound 5l seems to be a promising lead compound for the treatment of Alzheimer's diseases.

  3. Synthesis and biological evaluation of N-(carbobenzyloxy)-l-phenylalanine and N-(carbobenzyloxy)-l-aspartic acid-β-benzyl ester derivatives as potent topoisomerase IIα inhibitors.

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    Han, Xiaoyan; Zhong, Yifan; Zhou, Guan; Qi, Hui; Li, Shengbin; Ding, Qiang; Liu, Zhenming; Song, Yali; Qiao, Xiaoqiang

    2017-06-15

    A new series of thirteen N-(carbobenzyloxy)-l-phenylalanine and N-(carbobenzyloxy)-l-aspartic acid-β-benzyl ester compounds were synthesized and evaluated for antiproliferative activity against four different human cancer cell lines: cervical cancer (HeLa), lung cancer (A549), gastric cancer (MGC-803) and breast cancer (MCF-7) as well as topoisomerase I and IIα inhibitory activity. Compounds (5a, 5b, 5e, 8a, 8b) showed significant antiproliferative activity with low IC 50 values against the four cancer cell lines. Equally, compounds 5a, 5b, 5e, 5f, 8a, 8d, 8e and 8f showed topoisomerase IIα inhibitory activity at 100μM with 5b, 5e, 8f exhibiting potential topoisomerase IIα inhibitory activity compared to positive control at 100μM and 20μM, respectively. Conversely compounds 5e, 5f, 5g and 8a showed weaker topoisomerase I inhibitory activity compared to positive control at 100μM. Compound 5b exhibited the most potent topoisomerase IIα inhibitory activity at low concentration and better antiproliferative activity against the four human cancer cell lines. The molecular interactions between compounds 5a-5g, 8a-8f and the topoisomerase IIα (PDB ID: 1ZXM) were further investigated through molecular docking. The results indicated that these compounds could serve as promising leads for further optimization as novel antitumor agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding site acetylcholinesterase inhibitors.

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    Alipour, Masoumeh; Khoobi, Mehdi; Foroumadi, Alireza; Nadri, Hamid; Moradi, Alireza; Sakhteman, Amirhossein; Ghandi, Mehdi; Shafiee, Abbas

    2012-12-15

    A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC(50) in which compound 3r (IC(50) = 0.11 nM) was the most active compound against acetylcholinesterase enzyme. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. THE STUDY OF HYPOGLYCEMIC ACTIVITY OF 3-BENZYL-8-METHYLXANTHINE DERIVATIVES

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    I. М. Bilay

    2015-04-01

    Full Text Available Diabetes mellitus is a chronic endocrine disease. It etiology is the impact of both endogenous (genetic and exogenous factors that cause absolute or relative shortage of insulin or not effective use of it, which in turn leads to disruption of all kinds of substances exchange. The study of this problem is actual due to the high prevalence of diabetes, chronic disease, the tendency to increase the number of patients, their high morbidity and mortality. Diabetes is characterized by high blood glucose levels, which eventually leads to various complications associated with many human systems damage. Hormones (insulin and its analogues and synthetic drugs (sulfonylureas, biguanides etc. are used For the treatment of diabetes, but their high toxicity, cumulativeness, various side effects (autoimmunization, cutaneous allergic reactions, disturbance of the micro flora of the digestive tract, and the formation of insulin resistance restrict the use of these drugs in clinical practice. On this aspect the attention of researchers is attracted to xanthine derivatives, which are known as substances with wide range of biological activities including hypoglycemic. Based on the above, the search and development of new drugs among new 3-R-substituted xanthine, which would have hypoglycemic effect and would be deprived of most side effects is an acute problem of modern medical and pharmaceutical sciences. The aim of this study was to investigate the hypoglycemic activity of newly synthesized derivatives of 3-benzyl-8-methylxanthine and establish certain patterns "structure-activity" relationship. Materials and methods As objects of study for hypoglycemic activity we used derivatives of 3-benzyl-8-methylxanthine synthesized at the Department of Biochemistry and LaboratoryDiagnostics ofZaporizhzhyaStateMedicalUniversity. Hypoglycemic action of xanthine derivatives evaluated by intraperitoneal glucose tolerance test, which was reproduced by injection to animals

  6. Implications of the use of the labelled benzyl guanidine derivatives in nuclear medicine

    International Nuclear Information System (INIS)

    Zhagar, I.

    1994-01-01

    The development and synthesis of various labelled benzyl guanidine derivatives is described. After a brief outline of the tracer characteristics and the whole body imaging with 131- I -MIBG, 'pitfalls' of the visualization of sympathochromafine tissues and the possibilities of various pharmacological impacts on scintigraphy are discussed. Special emphasis is given to dosimetric and methodological aspects of MIBG scintigraphy in children, as well as to some new diagnostic applications of labelled benzyl guanidine in cardiology and pulmology. Whole body scintigraphy with 131-I-MIBG performed in groups of patients with pheochromocytoma, paraganglioma, neuroblastoma, medullary thyroid carcinoma, carcinoid and malignant insulinoma. Tumor, myocardial and salivary gland uptake of MIBG were estimated semi quantitatively, according to the method of Nakajo. The uptake of 131-I-MIBG was calculated from the activity measured prior and after the application and images acquired and was expressed as percent of dose administered.The results obtained confirm the high sensitivity and specificity of 131- I - MIBG in the scintigraphic evaluation of pheochromocytoma and euroblastoma. In medullary thyroid carcinoma it was found less sensitive than 99m Tc(V) -DMS A scan. The clinical evolution and uptake values were very well correlated. In patients developing bone marrow infiltration, uptake in primary tumor diminished. Good response to operative therapy in pheochromocytoma patients as well as to chemotherapy with neuroblastoma, was associated with an increase of myocardial MIBG uptake. There was highly significant negative correlation between myocardial uptake of MIBG and urinary catecholamine concentrations. Results obtained in determination 131- I -MIBG uptake in some neural crest tumors lead to the conclusion that the choice of background regions of interest can significantly influence the final results of quantification. (author)

  7. Synchronous scanning derivative spectrofluorimetry for the determination of cadmium with benzyl-2-pyridylketone 2-quinolylhydrazone

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, F.G.; Navas, A.; Santiago, M. (Malaga Univ. (Spain). Dept. of Analytical Chemistry)

    1985-01-01

    Synchronous scanning derivative spectrofluorimetry is used to determine cadmium by means of the fluorescent chelate formed with benzyl-2-pyridylketone 2-quinolylhydrazone at an apparent pH of 11 in 80% (v/v) ethanol. The normal spectrofluorimetric method is also described. The limits of detection are 0.7 and 4.1 ng Cd/sup 2 +/ ml/sup -1/, for the first derivative and normal techniques, respectively. Interferences in both methods are reported.

  8. Synthesis, physical-chemical and biological properties of 7-benzyl-3-methyl-8-thioxanthine derivatives

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    D. H. Ivanchenko

    2017-12-01

    Full Text Available Introduction . Interest to the problem of creating new effective antimicrobial agents among xanthine derivatives does not decrease. Primarily, this is due to the increasing of microbial resistance to conventional antimicrobial agents and the emergence of their new strains. In recent years interest to the therapeutic use of antioxidants in the treatment of diseases associated with oxidative stress has increased. The aim of this work is to elaborate simple laboratory methods of 7-benzyl-3-methyl-8-thioxanthine derivatives synthesis, unspecified in scientific papers earlier, and to study their physical, chemical and biological properties. Materials and methods. The melting point has been determined with the help of an open capillary method with PTP-M device. Elemental analysis has been performed with the help of the instrument Elementar Vario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO, internal standard – TMS. Study of antimicrobial and antifungal activity of synthesized compounds has been performed by two-fold serial dilution method. Standard test strains have been used for the study: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Dimethylsulfoxide was used as the solvent of the compounds. Results. Under short-time heating up of the initial 7-benzyl-3-methyl-8-thioxanthine with alkyl, alkenyl, benzyl halides or heteroalkylchlorides in a water-propanol-2 mixture in the presence of an equimolar amount of sodium hydroxide leads to the formation of 8-S-substituted of 7-benzyl-3-methylxanthines. Structure of synthesized compounds was definitely proved by NMR-spectroscopy. We conducted primary screening research of antimicrobial activity of 7-benzyl-3-methyl-8-thioxanthine derivatives, which revealed moderate and weak activity in concentrations 50-100 mcg/ml. Most of the obtained compounds showed a

  9. Quantitative Structure-Activity Relationship of Insecticidal Activity of Benzyl Ether Diamidine Derivatives

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    Zhai, Mengting; Chen, Yan; Li, Jing; Zhou, Jun

    2017-12-01

    The molecular electrongativity distance vector (MEDV-13) was used to describe the molecular structure of benzyl ether diamidine derivatives in this paper, Based on MEDV-13, The three-parameter (M 3, M 15, M 47) QSAR model of insecticidal activity (pIC 50) for 60 benzyl ether diamidine derivatives was constructed by leaps-and-bounds regression (LBR) . The traditional correlation coefficient (R) and the cross-validation correlation coefficient (R CV ) were 0.975 and 0.971, respectively. The robustness of the regression model was validated by Jackknife method, the correlation coefficient R were between 0.971 and 0.983. Meanwhile, the independent variables in the model were tested to be no autocorrelation. The regression results indicate that the model has good robust and predictive capabilities. The research would provide theoretical guidance for the development of new generation of anti African trypanosomiasis drugs with efficiency and low toxicity.

  10. Design, synthesis and biological evaluation of new hybrid anticonvulsants derived from N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide and 2-(2,5-dioxopyrrolidin-1-yl)butanamide derivatives.

    Science.gov (United States)

    Kamiński, Krzysztof; Rapacz, Anna; Łuszczki, Jarogniew J; Latacz, Gniewomir; Obniska, Jolanta; Kieć-Kononowicz, Katarzyna; Filipek, Barbara

    2015-05-15

    The purpose of this study was to synthesize the library of 33 new N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamides, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanamides, and 2-(2,5-dioxopyrrolidin-1-yl)butanamides as potential new hybrid anticonvulsant agents. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. The coupling reaction of the 2-(2,5-dioxopyrrolidin-1-yl)propanoic acid, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid, or 2-(2,5-dioxopyrrolidin-1-yl)butanoic acid with the appropriately substituted benzylamines in the presence of the coupling reagent, N,N-carbonyldiimidazole (CDI) generated the final compounds 4-36. Spectral data acquired via (1)H NMR, (13)C NMR, and LC-MS confirmed the chemical structures of the newly prepared compounds. The initial anticonvulsant screening was performed in mice intraperitoneally (ip), using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The rotarod test determined the acute neurological toxicity (NT). The results of preliminary pharmacological screening revealed that 25 compounds showed protection in half or more of the animals tested in the MES and/or scPTZ seizure models at the fixed dose of 100mg/kg. The broad spectra of activity across the preclinical seizure models displayed compounds 4, 7, 8, 13, 15-18, 24, and 26. The quantitative pharmacological studies in mice demonstrated the highest protection for compounds 4 (ED50 MES=67.65 mg/kg, ED50scPTZ=42.83 mg/kg); 8 (ED50 MES=54.90 mg/kg, ED50scPTZ=50.29 mg/kg); and 20 (ED50scPTZ=47.39 mg/kg). These compounds were distinctly more potent and provided better safety profiles in the rotarod test compared to valproic acid or ethosuximide, which were used as model AEDs. Compound 8 underwent only a slight metabolic change by the human liver microsomes (HLMs), and also did not affect the activity of human cytochrome P450 isoform

  11. Antioxidant activity of the new thiosulfinate derivative, S-benzyl phenylmethanethiosulfinate, from Petiveria alliacea L.

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    Okada, Youji; Tanaka, Kaoru; Sato, Eisuke; Okajima, Haruo

    2008-03-21

    The antioxidant effects of the new thiosulfinate derivative, S-benzyl phenylmethanethiosulfinate (BPT), against the oxidation of cumene and methyl linoleate (ML) in chlorobenzene were studied in detail using HPLC. The results showed that BPT provided effective inhibition with a well-defined induction period under these oxidation conditions, and it was found that the stoichiometric factor (n), the number of peroxyl radicals trapped by one antioxidant molecule, of BPT is about 2. We then undertook a thorough investigation aimed at elucidating the active structural site of BPT. Various model compounds, such as diphenyl disulfide, dibenzyl disulfide, S-phenyl benzenethiosulfinate and S-ethyl phenylmethanethiosulfinate, were used which provided evidence that the benzylic hydrogen of BPT is mainly associated with the peroxyl radical scavenging. Moreover, we measured the rate constant for the reaction of BPT with peroxyl radicals derived from cumene and ML in chlorobenzene, and based on these measurements, BPT reacts with these peroxyl radicals with a rate constant of k(inh) = 8.6 x 10(3) and 6.2 x 10(4) M(-1) s(-1), respectively.

  12. Asymmetric Benzylic Allylic Alkylation Reaction of 3-Furfural Derivatives by Dearomatizative Dienamine Activation.

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    He, Xiao-Long; Zhao, Hui-Ru; Duan, Chuan-Qi; Han, Xu; Du, Wei; Chen, Ying-Chun

    2018-04-20

    The dearomatizative dienamine-type ortho-quinodimethane species are smoothly generated between 2-alkyl-3-furfurals and chiral secondary amine catalysts, which undergo asymmetric benzylic allylic alkylation reactions with 2-nitroallylic acetates efficiently. A spectrum of densely functionalized 3-furfural derivatives are delivered in moderate to high yields with good to excellent diastereo- and enantioselectivity (up to 98 % yield, >19:1 d.r., >99 % ee). The latent transformations allow the facile production of some enantioenriched architectures, such as 1,1,2,2-tetraarylethanes and triarylmethanes, which are not easily available from other protocols. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P₁ agonists.

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    Tsuji, Takashi; Suzuki, Keisuke; Nakamura, Tsuyoshi; Goto, Taiji; Sekiguchi, Yukiko; Ikeda, Takuya; Fukuda, Takeshi; Takemoto, Toshiyasu; Mizuno, Yumiko; Kimura, Takako; Kawase, Yumi; Nara, Futoshi; Kagari, Takashi; Shimozato, Takaichi; Yahara, Chizuko; Inaba, Shinichi; Honda, Tomohiro; Izumi, Takashi; Tamura, Masakazu; Nishi, Takahide

    2014-08-01

    We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Synthesis, PASS-Predication and in Vitro Antimicrobial Activity of Benzyl 4-O-benzoyl-α-l-rhamnopyranoside Derivatives

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    Mohammed Mahbubul Matin

    2016-08-01

    Full Text Available Benzyl α-l-rhamnopyranoside 4, obtained by both conventional and microwave assisted glycosidation techniques, was subjected to 2,3-O-isopropylidene protection to yield compound 5 which on benzoylation and subsequent deprotection of isopropylidene group gave the desired 4-O-benzoylrhamnopyranoside 7 in reasonable yield. Di-O-acetyl derivative of benzoate 7 was prepared to get newer rhamnopyranoside. The structure activity relationship (SAR of the designed compounds was performed along with the prediction of activity spectra for substances (PASS training set. Experimental studies based on antimicrobial activities verified the predictions obtained by the PASS software. Protected rhamnopyranosides 5 and 6 exhibited slight distortion from regular 1C4 conformation, probably due to the fusion of pyranose and isopropylidene ring. Synthesized rhamnopyranosides 4–8 were employed as test chemicals for in vitro antimicrobial evaluation against eight human pathogenic bacteria and two fungi. Antimicrobial and SAR study showed that the rhamnopyranosides were prone against fungal organisms as compared to that of the bacterial pathogens. Interestingly, PASS prediction of the rhamnopyranoside derivatives 4–8 were 0.49 < Pa < 0.60 (where Pa is probability ‘to be active’ as antibacterial and 0.65 < Pa < 0.73 as antifungal activities, which showed significant agreement with experimental data, suggesting rhamnopyranoside derivatives 4–8 were more active against pathogenic fungi as compared to human pathogenic bacteria thus, there is a more than 50% chance that the rhamnopyranoside derivative structures 4–8 have not been reported with antimicrobial activity, making it a possible valuable lead compound.

  15. Synthesis and physical-chemical properties of functional derivatives of 3-benzyl-8-propylxanthinyl-7-acetic acid

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    E. K. Mikhal’chenko

    2017-08-01

    Full Text Available Introduction. Synthetic research of new biologically active compounds occupies an important place in modern pharmaceutical science.Thus it is important to develop techniques for the biologically active substances functionalization. Esters and amides take special place among the variety of functional derivatives of organic acids,. These fragments are well-known pharmacophores and could be found in a wide range of drugs. Thus, the nootropic agent pyracetam is 2-oxo-1-pyrolidineacetamide, and is the selective antagonist of β-adrenoreceptores; atenolol is a derivative of benzeneacetamide. Substituted acetamide and ester fragments are also present in the structures of aprofen, spasmolitin, acetylidine and β-lactam cephalosporins and penicillins antibiotics.Aim of our research was the synthetic method development for functional derivatives of 3-benzyl-8-propylxanthinyl-7-acetic acid and the study of their physical-chemical properties. Materials and methods. Melting points were determined using capillary method on DMP (M. 1Н NMR-spectra were recorded by Varian Mercury VX-200 device (company «Varian» – USA solvent – (DMSO-d6, internal standard – ТМS. Elemental analysis of obtained compounds was produced on device Elementar Vario L cube. Chemical shifts were reported in ppm (parts per million values. Infrared (IR spectra were measured on a Bruker Alpha instrument using a potassium bromide (KBr disk, scanning from 400 to 4000 cm-1. Results and discussion. We selected 3-benzyl-8-propylxanthinyl-7-acetic acid as initial compound for our study. For synthesis of hexyl, heptyl, octyl, nonyl, decyl and benzyl esters of 3-benzyl-8-propylxanthinyl-7-acetic acid we used alternative method, that included alkylation of sodium salts of acids with alkyl halogens. Reaction was made at DMF medium by reflux of reagents. Next stage of our research was the synthesis of amides of 3-beznyl-8-propylxanthinyl-7-acetic acid by the reaction of ethyl or propyl esters

  16. Synthesis and physical-chemical properties of 3-benzyl-8-propylxanthinyl-7-acetic acid and its derivatives

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    E. K. Mikhalchenko

    2017-04-01

    Full Text Available Introduction. Heterocyclic compounds play an important role in the metabolic processes of human organism. Structures of vitamins, nucleotides, chromoproteins are based on Nitrogen-containing heterocycles (purine, pyrimidine, thiazole etc. Thus, it was obvious to use these organic substances as basic molecules for synthetic research of biologically active compounds which could be used for treatment of different pathological processes. In their research, some scientist pay special attention to xanthine derivatives that are well-known low toxic natural compounds with wide spectrum of pronounced pharmacological properties (antioxidant, diuretic, antibacterial, anti-inflammatory etc. Insertion of carboxyl group in the structure of xanthine molecule is a prospective ability of its synthetic potential increasing. Aim of our research was the development of method of 3-benzyl-8-propylxanthinyl-7-acetic acid and its derivatives synthesis and studying their physical-chemical properties. Materials and methods. Melting points were determined using capillary method on DMP (M. 1Н NMR-spectra were recorded by Varian Mercury VX-200 device (company «Varian», USA solvent – (DMSO-d6, internal standard – ТМS. Elemental analysis of obtained compounds was produced on device Elementar Vario L cube. Results and discussion. We selected 3-benzyl-8-propyl xanthine as initial compound for our study. By its interaction with chloroacetic acid, chloroacetamide or propyl chloroacetate in DMF in the presence of calculated amount of NaHCO3 we synthesized 3-benzyl-8-propylxanthinyl-7-acetic acid its ester and amide. At the same time we found that obtaining of xanthinyl-7-acetic acid by hydrolysis of its ester produced with higher yield. On the next stage of our research we synthesized a number of water-soluble salts of 3-benzyl-8-propylxanthinyl-7-acetic acid by reaction of acid with different primary and secondary amines. The structures of all obtained compounds were

  17. Primary amino acid derivatives: substitution of the 4'-N'-benzylamide site in (R)-N'-benzyl 2-amino-3-methylbutanamide, (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide, and (R)-N'-benzyl 2-amino-3-methoxypropionamide provides potent anticonvulsants with pain-attenuating properties.

    Science.gov (United States)

    King, Amber M; Salomé, Christophe; Salomé-Grosjean, Elise; De Ryck, Marc; Kaminski, Rafal; Valade, Anne; Stables, James P; Kohn, Harold

    2011-10-13

    Recently, we reported that select N'-benzyl 2-substituted 2-amino acetamides (primary amino acid derivatives (PAADs)) exhibited pronounced activities in established whole animal anticonvulsant (i.e., maximal electroshock seizure (MES)) and neuropathic pain (i.e., formalin) models. The anticonvulsant activities of C(2)-hydrocarbon N'-benzyl 2-amino acetamides (MES ED(50) = 13-21 mg/kg) exceeded those of phenobarbital (ED(50) = 22 mg/kg). Two additional studies defining the structure-activity relationship of PAADs are presented in this issue of the journal. In this study, we demonstrated that the anticonvulsant activities of (R)-N'-benzyl 2-amino-3-methylbutanamide and (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide were sensitive to substituents at the 4'-N'-benzylamide site; electron-withdrawing groups retained activity, electron-donating groups led to a loss of activity, and incorporating either a 3-fluorobenzyloxy or 3-fluorophenoxymethyl group using a rationally designed multiple ligand approach improved activity. Additionally, we showed that substituents at the 4'-N'-benzylamide site of (R)-N'-benzyl 2-amino-3-methoxypropionamide also improved anticonvulsant activity, with the 3-fluorophenoxymethyl group providing the largest (∼4-fold) increase in activity (ED(50) = 8.9 mg/kg), a value that surpassed phenytoin (ED(50) = 9.5 mg/kg). Collectively, the pharmacological findings provided new information that C(2)-hydrocarbon PAADs represent a novel class of anticonvulsants.

  18. 1-Benzyl-2-Phenylbenzimidazole (BPB, a Benzimidazole Derivative, Induces Cell Apoptosis in Human Chondrosarcoma through Intrinsic and Extrinsic Pathways

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    Ju-Fang Liu

    2012-12-01

    Full Text Available In this study, we investigated the anticancer effects of a new benzimidazole derivative, 1-benzyl-2-phenyl -benzimidazole (BPB, in human chondrosarcoma cells. BPB-mediated apoptosis was assessed by the MTT assay and flow cytometry analysis. The in vivo efficacy was examined in a JJ012 xenograft model. Here we found that BPB induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 but not in primary chondrocytes. BPB induced upregulation of Bax, Bad and Bak, downregulation of Bcl-2, Bid and Bcl-XL and dysfunction of mitochondria in chondrosarcoma. In addition, BPB also promoted cytosolic releases AIF and Endo G. Furthermore, it triggered extrinsic death receptor-dependent pathway, which was characterized by activating Fas, FADD and caspase-8. Most importantly, animal studies revealed a dramatic 40% reduction in tumor volume after 21 days of treatment. Thus, BPB may be a novel anticancer agent for the treatment of chondrosarcoma.

  19. Synthesis and evaluation of radioiodinated (S,S)-2-({alpha}-(2-iodophenoxy)benzyl)morpholine for imaging brain norepinephrine transporter

    Energy Technology Data Exchange (ETDEWEB)

    Kanegawa, Naoki; Kimura, Hiroyuki; Sugita, Taku; Kajiyama, Satomi; Kuge, Yuji; Saji, Hideo [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Sakyo-ku, Kyoto (Japan); Kiyono, Yasushi [Kyoto University, Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Sakyo-ku, Kyoto (Japan); Kawashima, Hidekazu [Kyoto University, Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Sakyo-ku, Kyoto (Japan); Ueda, Masashi [Kyoto Prefectural University of Medicine, Radioisotope Laboratory, Sakyo-ku, Kyoto (Japan)

    2006-06-15

    Abnormality of the brain norepinephrine transporter (NET) has been reported in several psychiatric and neuronal disorders. Since NET is an important target for the diagnosis of these diseases, the development of radiopharmaceuticals for imaging of brain NET has been eagerly awaited. In this study, we synthesized (S,S)-2-({alpha}-(2-iodophenoxy)benzyl)morpholine [(S,S)-IPBM], a derivative of reboxetine iodinated at position 2 of the phenoxy ring, and evaluated its potential as a radiopharmaceutical for imaging brain NET using SPECT. (S,S)-{sup 123/125}I-IPBM was synthesized in a halogen exchange reaction. The affinity and selectivity of (S,S)-IPBM for NET was measured by assaying the displacement of {sup 3}H-nisoxetine and (S,S)-{sup 125}I-IPBM from the binding site in rat brain membrane, respectively. The biodistribution of (S,S)-{sup 125}I-IPBM was also determined in rats. Furthermore, SPECT studies with (S,S)-{sup 123}I-IPBM were carried out in the common marmoset. (S,S)-{sup 125}I-IPBM was prepared with high radiochemical yields (65%) and high radiochemical purity (>98%). (S,S)-IPBM showed high affinity and selectivity for NET in the binding assay experiments. In biodistribution experiments, (S,S)-{sup 125}I-IPBM showed rapid uptake in the brain, and the regional cerebral distribution was consistent with the density of NET. The administration of nisoxetine, a selective NET-binding agent, decreased the accumulation of (S,S)-{sup 125}I-IPBM in the brain, but the administration of selective serotonin transporter and dopamine transporter binding agents caused no significant changes in the accumulation. Moreover, (S,S)-{sup 123}I-IPBM allowed brain NET imaging in the common marmoset with SPECT. These results suggest that (S,S)-{sup 123}I-IPBM is a potential SPECT radiopharmaceutical for imaging brain NET. (orig.)

  20. Design, synthesis, and antifungal activities of novel triazole derivatives containing the benzyl group

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    Xu K

    2015-03-01

    Full Text Available Kehan Xu,1,* Lei Huang,1,* Zheng Xu,2 Yanwei Wang,1,3 Guojing Bai,1 Qiuye Wu,1 Xiaoyan Wang,1 Shichong Yu,1 Yuanying Jiang1 1School of Pharmacy, Second Military Medical University, Shanghai, 2Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 3Number 422 Hospital of PLA, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Abstract: In previous studies undertaken by our group, a series of 1-(1H-1,2,4-triazole-1-yl-2-(2,4-difluorophenyl-3-substituted-2-propanols (1a–r, which were analogs of fluconazole, was designed and synthesized by click chemistry. In the study reported here, the in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi. Compounds 1a, 1q, and 1r showed the more antifungal activity than the others. Keywords: triazole, synthesis, antifungal activity, CYP51

  1. Benzyl Alcohol Topical

    Science.gov (United States)

    Benzyl alcohol lotion is used to treat head lice (small insects that attach themselves to the skin) in adults ... children less than 6 months of age. Benzyl alcohol is in a class of medications called pediculicides. ...

  2. Highly Selective Liquid-Phase Benzylation of Anisole with Solid-Acid Zeolite Catalysts

    DEFF Research Database (Denmark)

    Poreddy, Raju; Shunmugavel, Saravanamurugan; Riisager, Anders

    2015-01-01

    Zeolites were evaluated as solid acid catalysts for the liquid-phase benzylation of anisole with benzyl alcohol, benzyl bromide, and benzyl chloride at 80 °C. Among the examined zeolites, H-mordenite-10 (H-MOR-10) demonstrated particular high activity (>99 %) and excellent selectivity (>96...

  3. Benzyl alcohol derivatives from the mushroom Hericium erinaceum attenuate LPS-stimulated inflammatory response through the regulation of NF-κB and AP-1 activity.

    Science.gov (United States)

    Noh, Hyung Jun; Yoon, Ju Young; Kim, Geum Sook; Lee, Seung Eun; Lee, Dae Young; Choi, Je Hun; Kim, Seung Yu; Kang, Ki Sung; Cho, Jae Youl; Kim, Ki Hyun

    2014-10-01

    On the search for anti-inflammatory compounds from natural Korean medicinal sources, a bioassay-guided fractionation and chemical investigation of the MeOH extract from the fruiting bodies of Hericium erinaceum resulted in the isolation and identification of five benzyl alcohol derivatives (1-5). In this study, their anti-inflammatory effects on lipopolysaccharide (LPS)-induced production of pro-inflammatory mediators were examined using RAW 264.7 macrophage cells. The structures of isolates were identified by comparing their spectroscopic data with previously reported values. The analysis of their inhibitory activities on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 macrophage cells showed that erinacerin B (2) and hericenone E (4) decreased the levels of NO and PGE2 production in a concentration-dependent manner. Next, this study was performed to examine their mechanism of action on the regulation of NO and PGE2 production. Compounds 2 and 4 were found to block the LPS-induced phosphorylation of two major inflammatory transcription factors, NF-κB (p65/p50) and AP-1 (c-Jun and c-Fos). Taken together, these results suggest that down-regulation of LPS-induced NO and PGE2 production by compounds 2 and 4 is mediated through the modulation of NF-κB and AP-1 activation in macrophage cells. These results impact the development of potential health products for preventing and treating inflammatory diseases.

  4. Ultraviolet photodissociation dynamics of the benzyl radical.

    Science.gov (United States)

    Song, Yu; Zheng, Xianfeng; Lucas, Michael; Zhang, Jingsong

    2011-05-14

    Ultraviolet (UV) photodissociation dynamics of jet-cooled benzyl radical via the 4(2)B(2) electronically excited state is studied in the photolysis wavelength region of 228 to 270 nm using high-n Rydberg atom time-of-flight (HRTOF) and resonance enhanced multiphoton ionization (REMPI) techniques. In this wavelength region, H-atom photofragment yield (PFY) spectra are obtained using ethylbenzene and benzyl chloride as the precursors of benzyl radical, and they have a broad peak centered around 254 nm and are in a good agreement with the previous UV absorption spectra of benzyl. The H + C(7)H(6) product translational energy distributions, P(E(T))s, are derived from the H-atom TOF spectra. The P(E(T)) distributions peak near 5.5 kcal mol(-1), and the fraction of average translational energy in the total excess energy, , is ∼0.3. The P(E(T))s indicate the production of fulvenallene + H, which was suggested by recent theoretical studies. The H-atom product angular distribution is isotropic, with the anisotropy parameter β ≈ 0. The H/D product ratios from isotope labeling studies using C(6)H(5)CD(2) and C(6)D(5)CH(2) are reasonably close to the statistical H/D ratios, suggesting that the H/D atoms are scrambled in the photodissociation of benzyl. The dissociation mechanism is consistent with internal conversion of the electronically excited benzyl followed by unimolecular decomposition of the hot benzyl radical on the ground state.

  5. An Optimized Synthesis, Molecular Structure and Characterization of Benzylic Derivatives of 1,2,4-Triazin-3,5(2H,4H-dione

    Directory of Open Access Journals (Sweden)

    Long-Chih Hwang

    2017-11-01

    Full Text Available 4-Benzyl-1,2,4-triazin-3,5(2H,4H-dione (3-benzyl-6-azauracil, 2, and 2,4-dibenzyl-1,2,4-triazin-3,5(2H,4H-dione (1,3-dibenzyl-6-azauracil, 3 were synthesized by the reaction of 1,2,4-triazin-3,5(2H,4H-dione (6-azauracil, 1 with benzyl bromide and potassium carbonate in dry acetone via the 18-crown-6-ether catalysis. In these reaction methods, we developed more convenient and efficient methodologies to afford compounds 2 and 3 in good yields. These compounds were characterized by 1H- and 13C-NMR, MS spectrum, IR spectroscopy and elemental analysis. The structure of 2 was verified by 2D-NMR measurements, including gHSQC and gHMBC measurements. A single-crystal X-ray diffraction experiment indicated that compound 3, with the molecular formula C17H15N3O2, crystallized from a CH3OH/CH2Cl2 diffusion solvent system in a monoclinic space group P21/c with a = 13.7844(13, b = 8.5691(8, c = 13.0527(12 Å, β = 105.961(2°, V = 1482.3(2 Å3, Z = 4, resulting in a density Dcalc of 1.314 g/cm3. The crystal structure of compound 3 is tightly stabilized by contact with five other molecules from the six short contacts formed by intermolecular C−O···H−Car, C−H···Car, and weakly π···π stacking interactions. The dihedral angle 31.90° is formed by the mean planes of the benzene rings of the N-2 and N-4 benzyl groups.

  6. Benzyl 2-((E-Tosyliminomethylphenylcarbamate

    Directory of Open Access Journals (Sweden)

    Kwang Min Ko

    2016-10-01

    Full Text Available Benzyl 2-((E-tosyliminomethylpenylcarbamate was prepared in good yield and characterized by the condensation reaction of benzyl 2-formylphenylcarbamate with p-toluenesulfonyl amine. The structure of the newly synthesized compound was determined using 1H, 13C-NMR, IR and mass spectral data.

  7. One-pot sequential synthesis of O-(halo-substituted benzyl hydroxylammonium salts

    Directory of Open Access Journals (Sweden)

    Saeed Emami

    2017-02-01

    Full Text Available In this study, we described a simple one-pot preparation of O-(halo-substituted benzyl hydroxylamine derivatives by O-benzylation of N-hydroxyurethane, followed by basic N-deprotection. The advantages of the method were the chemo- and regio-selectivity in obtaining the desired O-benzyl hydroxylammonium salts in a high yield as well as the simplicity of the purification process.

  8. Beyond benzyl grignards: facile generation of benzyl carbanions from styrenes.

    Science.gov (United States)

    Grigg, R David; Rigoli, Jared W; Van Hoveln, Ryan; Neale, Samuel; Schomaker, Jennifer M

    2012-07-23

    Benzylic functionalization is a convenient approach towards the conversion of readily available aromatic hydrocarbon feedstocks into more useful molecules. However, the formation of carbanionic benzyl species from benzyl halides or similar precursors is far from trivial. An alternative approach is the direct reaction of a styrene with a suitable coupling partner, but these reactions often involve the use of precious-metal transition-metal catalysts. Herein, we report the facile and convenient generation of reactive benzyl anionic species from styrenes. A Cu(I)-catalyzed Markovnikov hydroboration of the styrenic double bond by using a bulky pinacol borane source is followed by treatment with KOtBu to facilitate a sterically induced cleavage of the C-B bond to produce a benzylic carbanion. Quenching this intermediate with a variety of electrophiles, including CO(2), CS(2), isocyanates, and isothiocyanates, promotes C-C bond formation at the benzylic carbon atom. The utility of this methodology was demonstrated in a three-step, two-pot synthesis of the nonsteroidal anti-inflammatory drug (±)-flurbiprofen. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Design, synthesis and biological activity of novel donepezil derivatives bearing N-benzyl pyridinium moiety as potent and dual binding site acetylcholinesterase inhibitors.

    Science.gov (United States)

    Lan, Jin-Shuai; Zhang, Tong; Liu, Yun; Yang, Jing; Xie, Sai-Sai; Liu, Jing; Miao, Ze-Yang; Ding, Yue

    2017-06-16

    A series of new donepezil derivatives were designed synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase and self-induced β-amyloid (Aβ) aggregation, and moderate antioxidant activity. Especially, compound 5b presented the greatest ability to inhibit cholinesterase (IC 50 , 1.9 nM for eeAChE and 0.8 nM for hAChE), good inhibition of Aβ aggregation (53.7% at 20 μM) and good antioxidant activity (0.54 trolox equivalents). Kinetic and molecular modeling studies indicated that compound 5b was a mixed-type inhibitor, binding simultaneously to the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, compound 5b could reduce PC12 cells death induced by oxidative stress and Aβ (1-42). Moreover, in vivo experiments showed that compound 5b was nontoxic and tolerated at doses up to 2000 mg/kg. These results suggested that compound 5b might be an excellent multifunctional agent for AD treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Fragrance material review on benzyl alcohol.

    Science.gov (United States)

    Scognamiglio, J; Jones, L; Vitale, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of benzyl alcohol when used as a fragrance ingredient is presented. Benzyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for benzyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, toxicokinetics, repeated dose, reproductive toxicity, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Enhanced catalytic properties of mesoporous mordenite for benzylation of benzene with benzyl alcohol

    Energy Technology Data Exchange (ETDEWEB)

    Saxena, Sandeep K.; Viswanadham, Nagabhatla, E-mail: nagabhatla.viswanadham@gmail.com

    2017-01-15

    Graphical abstract: The nano size pores (∼10 nm) created in the microporous mordenite zeolite facilitated enhanced catalytic activity to produce as high as 97 wt.% yield of di-phenyl methane in the benzylation of benzene with benzyl alcohol at solvent-free liquid phase reaction conditions. - Highlights: • Nano pores of ∼10 nm size have been created in microporous mordenite. • Dealumination at optimized conditions resulted in enhanced properties of mordenite. • Hierarchically porous mordenite enhanced bulky catalytic reactions. • As high as 97% selectivity to Di-phenyl methane obtained. • Solvent-free, liquid phase alkylation catalyst with stable activity for reusability. - Abstract: Zeolite mordenite has been treated with nitric acid at different severities so as to facilitate the framework dealumination and optimization of the textural properties such as acidity and porosity. The samples obtained have been characterized by X-ray diffraction, FTIR, SEM, TEM, surface area, porosity by N{sub 2} adsorption and ammonia TPD. The resultant samples have been evaluated towards the bulky alkylation reaction of benzylation of benzene with benzyl alcohol. The studies indicated the improvement in the textural properties such as surface area, pore volume and acidity of the samples after the acid treatment. While, the phenomenon of enhancement in properties was exhibited by all the acid treated mordenite samples, the highest improvement in properties was observed at a particular condition of acid treatment (SM-2 sample). This particular sample also exhibited highest acidity and the presence of ∼10 nm size pores that resulted in the effective catalytic activity towards the bulky alkylation reaction of benzene with benzyl alcohol to produce high yields of di-phenyl methane.

  12. Synthesis and Anti-HIV-1 Activity of New MKC-442 Analogues with an Alkynyl-Substituted 6-Benzyl Group

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo

    2007-01-01

    Synthesis and antiviral activities are reported of a series of 6-(3-alkynyl benzyl)-substituted analogues of MKC-442 (6-benzyl-1-(ethoxymethyl)-5-isopropyluracil), a highly potent agent against HIV. The 3-alkynyl group is assumed to give a better stacking of the substituted benzyl group to reverse...... transcriptase (RT) and this was believed to improve antiviral activity against HIV-1. The bromo derivatives, 5-alkyl-6-(3-bromo-benzyl)-1-ethoxymethyl derivatives 7a, b and 5-alkyl-6-(3-bromobenzyl)-1-allyloxymethyl derivatives 9a, b, showed activity against HIV on the same level as their corresponding...

  13. Comparative Evaluation of Using NOTA and DOTA Derivatives as Bifunctional Chelating Agents in the Preparation of 68Ga-Labeled Porphyrin: Impact on Pharmacokinetics and Tumor Uptake in a Mouse Model.

    Science.gov (United States)

    Guleria, Mohini; Das, Tapas; Amirdhanayagam, Jeyachitra; Sarma, Haladhar D; Dash, Ashutosh

    2018-02-01

    Both NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) derivatives have been used as bifunctional chelating agents (BFCAs) for the preparation of 68 Ga-labeled target-specific agents having potential for positron emission tomography (PET) imaging of cancerous lesions. In the present work, the authors have attempted a comparative pharmacokinetic evaluation between 68 Ga-labeled porphyrins prepared using NOTA and DOTA derivatives as the BFCAs. A symmetrical porphyrin derivative, 5,10,15,20-tetrakis(p-carboxymethyleneoxyphenyl)porphyrin, was synthesized and coupled with two different BFCAs viz. p-NH 2 -benzyl-NOTA and p-NH 2 -benzyl-DOTA. Both the porphyrin-BFCA conjugates were radiolabeled with 68 Ga. A comparative bioevaluation involving pharmacokinetics and tumor affinity was performed in a tumor-bearing small animal model. Gallium-68-labeled porphyrin-amido-benzyl-NOTA and porphyrin-amido-benzyl-DOTA complexes were prepared with high radiochemical purity. Both radiolabeled complexes exhibited almost similar stability in human serum and near-identical tumor affinity and pharmacokinetic behavior in animal studies. The present study demonstrates that the pharmacokinetic behavior of 68 Ga-labeled porphyrin derivatives, prepared using either NOTA or DOTA derivatives as BFCAs, remains almost identical and hence both NOTA and DOTA derivatives could be considered equivalent for developing 68 Ga-based PET agents for imaging of tumorous lesions.

  14. Synthesis, characterization, computational studies and biological evaluation of S-benzyl-β-N-[3-(4-hydroxy-3-methoxy-phenylallylidene)]dithiocarbazate

    Science.gov (United States)

    Bhat, Rayees A.; Kumar, D.; Malla, Manzoor A.; Bhat, Sami U.; Khan, Md Shahzad; Manzoor, Ovais; Srivastava, Anurag; Naikoo, Rawoof A.; Mohsin, Mohd; Mir, Muzzaffar A.

    2018-03-01

    S-Benzyl-β-N-[3-(4-hydroxy-3-methoxy-phenylallylidene)]dithiocarbazate (HL1), Schiff base of S-benzyl dithiocarbazate, was synthesized by 1:1 condensation between S-benzyl dithiocarbazate and 4-hydroxy-3-methoxy cinnamaldehyde. The nitrogen-sulfur Schiff base (HL1) was characterized by Mass, FT-IR, H1-NMR, Raman, and UV-VIS spectroscopic techniques. Theoretical quantum chemical calculations were performed using DFT in combination with B3LYP exchange correlation functional and 6-311++ G (d, p) basis sets level. The calculated values of chemical potential (μ), HOMO-LUMO energy gap, chemical hardness, softness (S), ionization energy (IE), electron affinity (EA), dipole moment (D) and relative stabilization energy of the compound were 0.14881 eV, 0.12542 eV, 0.06271 eV, 3.37299 eV, -0.21152 eV, -0.08610 eV, 4.4090 Debye and -1753.350 eV respectively. Theoretically calculated parameters like H1-NMR, FT-IR, UV-VIS, Raman, electrostatic potential and HOMO-LUMO energy gap are in good agreement with experimental results. Also, in-vitro cytotoxicity studies were done against two habitually infection causing bacteria strains including gram-positive (S. aureus) and gram-negative (E. coli) for antibacterial activity. The results showed appreciable biological activity and the activity increased with increase in dose.

  15. Financial Derivatives (Based on Two Supports Evaluation

    Directory of Open Access Journals (Sweden)

    Tiberiu Socaciu

    2016-07-01

    Full Text Available In this paper we build a PDE like Black-Scholes equation in hypothesis of a financial derivative that is dependent on two supports (usual is dependent only on one support, like amoption based on gold, when national currency has a great float.Keywords: Financial derivatives, derivatives evaluation, derivatives based on two supports, extended Itō like lemma.

  16. Evaluation of radioiodinated (2S,{alpha}S)-2-({alpha}-(2-iodophenoxy)benzyl)morpholine as a radioligand for imaging of norepinephrine transporter in the heart

    Energy Technology Data Exchange (ETDEWEB)

    Kiyono, Yasushi [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan)], E-mail: ykiyono@u-fukui.ac.jp; Sugita, Taku [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Ueda, Masashi [Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Kawashima, Hidekazu [Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Kanegawa, Naoki; Kuge, Yuji [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Saji, Hideo [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)

    2008-02-15

    Introduction: The norepinephrine transporter (NET) is located presynaptically on noradrenergic nerve terminals and plays a critical role in the regulation of the synaptic norepinephrine (NE) concentration via the reuptake of NE. Changes in NET have been recently reported in several cardiac failures. Therefore, a NET-specific radioligand is useful for in vivo assessment of changes in NET density in various cardiac disorders. Recently, we developed a radioiodinated reboxetine analogue, (2S,{alpha}S)-2-({alpha}-(2-iodophenoxy)benzyl)morpholine ((S,S)-IPBM), for NET imaging. In the current study, we assessed the applicability of radioiodinated (S,S)-IPBM to NET imaging in the heart. Methods: The NET affinity and selectivity were measured from the ability to displace specific [{sup 3}H]nisoxetine and (S,S)-[{sup 125}I]IPBM binding to rat heart membrane, respectively. To evaluate the distribution of (S,S)-[{sup 125}I]IPBM in vivo, biodistribution experiment was performed in rats. With the use of several monoamine transporter binding agents, pharmacological blocking experiments were performed in rats. Results: In vitro binding assays showed that the affinity of (S,S)-IPBM to NET was similar to those of the well-known NET-specific binding agents, nisoxetine and desipramine. Furthermore, (S,S)-[{sup 125}I]IPBM binding was inhibited by nisoxetine and desipramine, but not by dopamine or serotonin transporter binding agents. These data indicated that (S,S)-IPBM had high affinity and selectivity for NET in vitro. Biodistribution studies in rats showed rapid and high uptake of (S,S)-[{sup 125}I]IPBM by the heart and rapid clearance from the blood. The heart-to-blood ratio was 31.9 at 180 min after the injection. The administration of nisoxetine and desipramine decreased (S,S)-[{sup 125}I]IPBM accumulation in the heart, but injection of fluoxetine and GBR12909 had little influence. Conclusions: Radioiodinated (S,S)-IPBM is a potential radioligand for NET imaging in the heart.

  17. Synthesis of benzyl chlorides and cycloveratrylene macrocycles using benzylic alcohols under homogeneous catalysis by HCl/dioxane

    Directory of Open Access Journals (Sweden)

    Yolanda Marina Vargas-Rodríguez

    2012-01-01

    Full Text Available The synthesis of benzyl chlorides, cyclic derivatives cyclotriveratrylene and cyclotripiperotrylene were carried out in using the HCl/dioxane system as a catalyst. The reaction proceeded with high selectivity and is sensitive to the number of alkyl and methoxy substituent on the aromatic ring.

  18. Design, synthesis and antimalarial activity of novel bis{N-[(pyrrolo[1,2-a]quinoxalin-4-yl)benzyl]-3-aminopropyl}amine derivatives.

    Science.gov (United States)

    Guillon, Jean; Cohen, Anita; Gueddouda, Nassima Meriem; Das, Rabindra Nath; Moreau, Stéphane; Ronga, Luisa; Savrimoutou, Solène; Basmaciyan, Louise; Monnier, Alix; Monget, Myriam; Rubio, Sandra; Garnerin, Timothée; Azas, Nadine; Mergny, Jean-Louis; Mullié, Catherine; Sonnet, Pascal

    2017-12-01

    Novel series of bis- and tris-pyrrolo[1,2-a]quinoxaline derivatives 1 were synthesized and tested for in vitro activity upon the intraerythrocytic stage of W2 and 3D7 Plasmodium falciparum strains. Biological results showed good antimalarial activity with IC 50 in the μM range. In attempting to investigate the large broad-spectrum antiprotozoal activities of these new derivatives, their properties toward Leishmania donovani were also investigated and revealed their selective antiplasmodial profile. In parallel, the in vitro cytotoxicity of these molecules was assessed on the human HepG2 cell line. Structure-activity relationships of these new synthetic compounds are discussed here. The bis-pyrrolo[1,2-a]quinoxalines 1n and 1p were identified as the most potent antimalarial candidates with selectivity index (SI) of 40.6 on W2 strain, and 39.25 on 3D7 strain, respectively. As the telomeres of the parasite could constitute an attractive target, we investigated the possibility of targeting Plasmodium telomeres by stabilizing the Plasmodium telomeric G-quadruplexes through a FRET melting assay by our new compounds.

  19. derivatives: Synthesis and antimicrobial evaluation

    Indian Academy of Sciences (India)

    cal activity study revealed that all compounds showed promising activities and bis-(1H-2-benzopyran-1-one) derivatives (5) ...... A and Galvez J 2004 Planta Med. 70 315. 6. ... Ante N, Erik De C, Jan B and Mladen M 2011 Molecules. 16 6023.

  20. Optimized Formation of Benzyl Isothiocyanate by Endogenous ...

    African Journals Online (AJOL)

    The formed benzyl isothiocyanate was extracted by steam distillation method and purified by thin-layer chromatography (TLC). Relevant process variables were also studied. Finally, the purified benzyl isothiocyanate was analyzed by gas chromatography-mass spectrometer (GC-MS) and compared to BITC standard.

  1. Optimized Formation of Benzyl Isothiocyanate by Endogenous ...

    African Journals Online (AJOL)

    Purpose: To use endogenous myrosinase in Carica papaya seed to convert benzyl glucosinolate (BG) to benzyl isothiocyanate (BITC) and then extract it for further studies. Methods: Process variables including seed powder particle size, sample-to-solvent ratio, pH of buffer solution, enzymolysis temperature, enzymolysis ...

  2. Dietary Exposure to Benzyl Butyl Phthalate in China

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lei; JIANG Ding Guo; SUI Hai Xia; WU Ping Gu; LIU Ai Dong; YANG Da Jin; LIU Zhao Ping; SONG Yan; LI Ning

    2016-01-01

    ObjectiveBenzyl butyl phthalate (BBP) is a plasticizer used in food contact materials. Dietary exposure to BBP might lead to reproduction and developmental damages to human. The present paper was aimed to assess the health risk of BBP dietary exposure in Chinese population. MethodsThe BBP contents were detected in 7409 food samples from 25 foodcategories by gas chromatography-mass spectrometry operated in selected ion monitoring (SIM) mode. The dietary exposures of BBP in different age and sex groups were estimated by combining the content data with food consumption data derived from 2002 China National Nutrient and Health Survey, and evaluated according to the tolerable daily intake (TDI) of BBP established by European Food safety Agency. ResultsIt was found that BBP was undetectable in most samples and the highest level was 1.69 mg/kg detected in a vegetable oil sample. The average dietary exposure of BBP in people aged≥2 years was 1.03 μg/kgbw perday and the highest average exposure was found in 2-6 years old children (1.98 μg/kg bw perday). The BBP exposure in 7-12 months old children excessed 10% of tolerable daily intake (TDI) in worst scenario. ConclusionThe health risk of BBP dietary exposure in Chinese population is low and, considering BBP alone, there is no safety concern.

  3. Resonance Raman study of benzyl radical

    DEFF Research Database (Denmark)

    Langkilde, F.W.; Bajdor, K.; Wilbrandt, R.

    1992-01-01

    Time-resolved resonance Raman spectra are obtained of benzyl radicals created by laser flash photolysis of benzylchloride and diphenylacetone in solution. The spectra are obtained in resonance with the intense 2 2A2-1 B-2(2) transition of benzyl. The strong Raman bands are assigned to totally...... symmetric a1 modes. The remaining observed bands are tentatively assigned to fundamental modes of b1, a2, and b2 symmetry, and to overtones and combinations. The resonance Raman spectra are found to be quite different from previous fluorescence spectra of benzyl, and the origins of these differences...

  4. Synthesis and Lateral Root-Inducing Activity of N-Benzyl-3-Substituted-2-Piperidones

    OpenAIRE

    Tsukada, Hidetaka; Itamura, Tomoaki; Ishii, Rika; Taniguchi, Eiji; Kuwano, Eiichi

    1999-01-01

    Thirty N-benzyl-3-substituted-2-piperidones were synthesized, and their plant growth regulatory activity was evaluated by using a lettuce seedling test. Most of the compounds at 100 ppm caused lateral root formation. Of the series of compounds tested, N-benzyl-3-[1-hydroxy-1-(4-quinolyl)methyl]-2-piperidone (30) showed the highest activity. When 1ppm of compound 30 was supplied to seedlings, 29% of the primary roots formed at least one lateral root.

  5. Synthesis, anticancer and antibacterial activity of salinomycin N-benzyl amides.

    Science.gov (United States)

    Antoszczak, Michał; Maj, Ewa; Napiórkowska, Agnieszka; Stefańska, Joanna; Augustynowicz-Kopeć, Ewa; Wietrzyk, Joanna; Janczak, Jan; Brzezinski, Bogumil; Huczyński, Adam

    2014-11-25

    A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position.

  6. Synthesis of selected 5-thio-substituted tetrazole derivatives and evaluation of their antibacterial and antifungal activities

    Directory of Open Access Journals (Sweden)

    NALILU SUCHETHA KUMARI

    2011-02-01

    Full Text Available Several 5-thio-substituted tetrazole derivatives were efficiently synthesized by a three-step process. The substituted tetrazol-5-thiol, namely, 1-benzyl-1H-tetrazole-5-thiol (2 was prepared by refluxing commercially available benzyl isothiocyanate (1 with sodium azide in water. The second step was the synthesis of 1-benzyl-5-[(3-bromopropylthio]-1H-tetrazole (3 by thioalkylation of tetrazole-5-thiol 2 with 1,3-dibromopropane in tetrahydrofuran. Finally, the 5-thio-substituted tetrazole derivatives 4a–i were prepared by condensation of 3 with the corresponding amine or thiol. The structures of the newly synthesized compounds were characterized by NMR, LC/MS/MS, IR spectral data and elemental analysis. All the synthesized compounds were screened for their antibacterial and antifungal activities.

  7. Thermodynamic and fluorescence studies of the underlying factors in benzyl alcohol-induced lipid interdigitated phase.

    Science.gov (United States)

    Chen, C H; Hoye, K; Roth, L G

    1996-09-15

    To further investigate factors contributing to the action of alcohol in the solute-induced lipid interdigitation phase, thermodynamic and fluorescence polarization measurements were carried out to study the interaction of benzyl alcohol with dipalmitoyl phosphatidylcholine bilayer vesicles. The obtained results were compared with those previously reported for ethanol and cyclohexanol (L. G. Roth and C-H. Chen, Arch. Biochem. Biophys. 296, 207, 1992). Similar to ethanol, benzyl alcohol was found to exhibit a biphasic effect on the enthalpy (delta Hm) and the temperature (tm) of the lipid-phase transition and the steady-state fluorescence polarization (P) monitored by 1,6-diphenyl-1,3,5-hexatriene. At a total concentration of benzyl alcohol delta Hm and P, which were correlated with the formation of a lipid interdigitated phase, as evidenced by reported X-ray diffraction data. Combining the results with benzyl alcohol and ethanol suggested that simultaneously large changes in delta Hm and P can be used as an indication of the occurrence of a solute-induced lipid interdigitated phase. The overall interacting force in the formation of this lipid phase, as derived from the interactions of the hydroxyl portion of an alcohol with the lipid phosphate head group and the hydrophobic portion of an alcohol with the lipid hydrocarbon chains, may or may not be dominated by hydrophobic interaction. Although lipid/water partition coefficients and the contribution of hydrophobic interaction to the overall interacting force were comparable between benzyl alcohol and cyclohexanol, benzyl alcohol induced lipid interdigitated phase, but not for cyclohexanol. This was due to the ability of benzyl alcohol to be more effective than cyclohexanol in simultaneously interacting with the phosphate head group and the hydrocarbon chains of lipid.

  8. Polycyclic Aromatic Compounds as Anticancer Agents: Synthesis and Biological Evaluation of Methoxy Dibenzofluorene Derivatives

    Directory of Open Access Journals (Sweden)

    Bimal Krishna Banik

    2014-08-01

    Full Text Available Synthesis of a new methoxy dibenzofluorene through alkylation, cyclodehydration and aromatization in a one-pot operation is achieved for the first time. Using this hydrocarbon, a few derivatives are prepared through aromatic nitration, catalytic hydrogenation, coupling reaction with a side chain and reduction. The benzylic position of this hydrocarbon with the side chain is oxidized and reduced. Some of these derivatives have demonstrated excellent antitumor activities in vitro. This study confirms antitumor activity depends on the structures of the molecules.

  9. Evaluation of the efficiency of Pd/H2 -catalyzed benzylic H/D exchange of dehydroabietinal with D(2) O and synthesis of a tritium-labeled analogue.

    Science.gov (United States)

    Petros, Robby A; Shah, Jyoti

    2014-01-01

    Dehydroabietinal (DA) has been identified as an important signaling molecule in systemic acquired resistance in plants. Deuterium and tritium-labeled DA were synthesized to confirm its role in signaling and to further elucidate the mechanism by which DA induces systemic acquired resistance. Pd/H2 -catalyzed exchange of benzylic hydrogen atoms of DA with (2) H-H2 O or (3) H-H2 O was conducted with >97% label incorporation for (2) H-DA and a specific activity of 12.6 mCi/mmol for (3) H-DA synthesized from 90 mCi/mmol (3) H-H2 O. The extent of deuterium labeling at each benzylic position was determined via an inverse-gated (13) C NMR experiment. C7 and C15 were 87% and 81% labeled, respectively. Isotope-induced chemical shift changes at C6 were used to approximate the amount of singly (66%) and doubly (17%) labeled (2) H-DA at C7. Results also indicated that two of the three benzylic protons in DA underwent facile exchange. Exchange at the remaining position was likely hampered by steric interactions of nearby methyl groups at the surface of the Pd catalyst. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Evaluation of antiproliferative activity of pyrazolothiazolopyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    N. S. Finiuk

    2018-04-01

    Full Text Available The research aim was to test cytotoxic effects in vitro of seven novel pyrazolothiazolopyrimidine derivatives in targeting several lines of tumor and pseudo-normal mammalian cells. We demonstrated that cytotoxic effects of these derivatives depended on the tissue origin of targeted cells. Leukemia cells were found to be the most sensitive to the action of compounds 2 and 7. Compound 2 demonstrated approximately two times higher toxicity towards the multidrug-resistant sub-line of HL-60/ADR cells compared to the Doxorubicin effect. Antiproliferative action of compounds 2 and 7 dropped in the order: leukemia > melanoma > hepatocarcinoma > glioblastoma > colon carcinoma > breast and ovarian carcinoma cells. These compounds were less toxic than Doxorubicin towards the non-tumor cells. The novel pyrazolothiazolopyrimidine, compound 2, demonstrated high toxicity towards human leukemia and, of special importance, towards multidrug-resistant leukemia cells, and low toxicity towards pseudo-normal cells.

  11. Conformational Studies on γ - Benzyl- L- Glutamate and L- Valine Containing Block Copolypeptides

    OpenAIRE

    Kumar, Ajay

    2010-01-01

    Conformational studies on γ - benzyl-L- glutamate and L- valine containing block copolypeptides are reported using IR and CD spectra. The block copolypeptides contain valine block in the center and on both sides of the valine are γ - benzyl- L- glutamate blocks. The changes in conformation with increase in chain length of γ - benzyl- L- glutamate blocks are observed. When the chain length of γ - benzyl-L- glutamate block is 13, the block copolypeptide crystallized into beta conformation. With...

  12. Crystal structures of HIV-1 nonnucleoside reverse transcriptase inhibitors: N-benzyl-4-methyl-benzimidazoles

    Science.gov (United States)

    Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.

    2009-07-01

    HIV-1 nonnucleoside reverse transcriptase inhibitors are potentially specific and effective drugs in AIDS therapy. The presence of two aromatic systems with an angled orientation in the molecule of the inhibitor is crucial for interactions with HIV-1 RT. The inhibitor drives like a wedge into the cluster of aromatic residues of RT HIV-1 and restrains the enzyme in a conformation that blocks the chemical step of nucleotide incorporation. Structural studies provide useful information for designing new, more active inhibitors. The crystal structures of four NNRTIs are presented here. The investigated compounds are derivatives of N-benzyl-4-methyl-benzimidazole with various aliphatic and aromatic substituents at carbon 2 positions and a 2,6-dihalogeno-substituted N-benzyl moiety. Structural data reported here show that the conformation of the investigated compounds is relatively rigid. Such feature is important for the nonnucleoside inhibitor binding to HIV-1 reverse transcriptase.

  13. Determination of the Antiproliferative Activity of New Theobromine Derivatives and Evaluation of Their In Vitro Hepatotoxic Effects.

    Science.gov (United States)

    Georgieva, Maya; Kondeva-Burdina, Magdalena; Mitkov, Javor; Tzankova, Virginia; Momekov, Georgi; Zlatkov, Alexander

    2016-01-01

    A new series of N-substituted 1-benzyltheobromine-8-thioacetamides were designed and synthesized. Their anti-proliferative activity against human chronic myelocytic leukemia cell K562, human T-cell leukemia cell SKW-3 and human acute myeloid leukemia HL-60 was evaluated. For the tested compounds a concentrationdependent cytotoxic activity was observed, with 7g outlined as the most active compound within the series. The targed compounds were obtained in yields of 56 to 85% and their structures were elucidated by FTIR, (1)H NMR, (13)C NMR and microanalyses. The compounds purity was proven by elemental analysis and spectral data. In general, the compounds showed low hepatotoxicity on sub-cellular and cellular level. On isolated rat microsomes only 7d showed toxic effect while theobromine, 1-benzyl-theobromine-thioacetic acid (BTTA) and the other new theobromine derivatives were devoid of toxicity. In isolated rat hepatocytes, when compared to theobromine and BTTA, 7f showed lower cytotoxic effects, and 7d exerted higher cytotoxicity. The results indicate 7g as a promising structure for the design of future compounds with low hepatotoxicity and good antiproliferative activity.

  14. Category 3 investigation-derived waste Readiness Evaluation Plan

    International Nuclear Information System (INIS)

    Ludowise, J.D.

    1996-08-01

    This Readiness Evaluation Plan presents the methodology used to assess the readiness for loading investigation-derived waste (IDW) drums on trucks for transport to the Environmental Restoration Disposal Facility (ERDF). The scope of this Readiness Evaluation Plan includes an assessment of the organizations, procedures, and regulatory approvals necessary for the handling of IDW containers and the subsequent transportation of materials to ERDF

  15. Benzylic monooxygenation catalyzed by toluene dioxygenase from Pseudomonas putida

    International Nuclear Information System (INIS)

    Wackett, L.P.; Kwart, L.D.; Gibson, D.T.

    1988-01-01

    Toluene dioxygenase, a multicomponent enzyme system known to oxidize mononuclear aromatic hydrocarbons to cis-dihydrodiols, oxidized indene and indan to 1-indenol and 1-indanol, respectively. In addition, the enzyme catalyzed dioxygen addition to the nonaromatic double bond of indene to form cis-1,2-indandiol. The oxygen atoms in 1-indenol and cis-1,2-indandiol were shown to be derived from molecular oxygen, whereas 70% of the oxygen in 1-indanol was derived from water. All of the isolated products were optically active as demonstrated by 19 F NMR and HPLC discrimination of diastereomeric esters and by chiroptic methods. The high optical purity of (-)-(1R)-indanol (84% enantiomeric excess) and the failure of scavengers of reactive oxygen species to inhibit the monooxygenation reaction supported the contention that monooxygen insertion is mediated by an active-site process. Experiments with 3-[ 2 H] indene indicated that equilibration between C-1 and C-3 occurred prior to the formation of the carbon-oxygen bond to yield 1-indenol. Naphthalene dioxygenase also oxidized indan to 1-indanol, which suggested that benzylic monoxygenation may be typical of this group of dioxygenases

  16. The Derivation of Evaluation Criteria of Nuclear Fuel Cycle

    International Nuclear Information System (INIS)

    Kim, S. K.; Ko, W. I.

    2013-01-01

    This study suggests the evaluation criteria and evaluation indicators derived using a factor analysis. As a result of a factor analysis, 5 evaluation criteria (safety (technological feature), environmental impact, economic feasibility, sociality, institution) and 24 evaluation indicators were selected. Particularly, the level of legislation for the management of radioactive waste, the level of establishment of safety standards of the country, and the level of application of international safety standards were analyzed to be qualitative evaluation indicators that should be considered in the aspect of the institution. The purpose of an analysis on diverse nuclear fuel cycles is to select the optimum nuclear fuel cycle suitable for the environment of one's own country. Accordingly, diverse evaluation criteria and evaluation indicators are necessary. In addition, individual evaluation criteria can be explained with various evaluation indicators. For example, the evaluation criteria for economic feasibility can be explained with evaluation indicators such as the unit cost or total cost. However, if too many evaluation indicators are included in one evaluation criterion, the evaluation is not easy, and if too few evaluation indicators are established, the evaluation criteria cannot be explained sufficiently, and thus the evaluation can be distorted. Accordingly, not only should the evaluation indicators be composed of an appropriate number of units, but they should also not be overlapped, and ambiguous evaluation indicators should be dropped out and necessary evaluation indicators must be included

  17. A Statistical Approach for Deriving Key NFC Evaluation Criteria

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S. K; Kang, G. B.; Ko, W. I [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Young, S. R.; Gao, R. X. [Univ. of Science and Technology, Daejeon (Korea, Republic of)

    2014-02-15

    This study suggests 5 evaluation criteria (safety and technology, environmental impact, economic feasibility, social factors, and institutional factors) and 24 evaluation indicators for a NFC (nuclear fuel cycle) derived using factor analysis. To do so, a survey using 1 on 1 interview was given to nuclear energy experts and local residents who live near nuclear power plants. In addition, by conducting a factor analysis, homogeneous evaluation indicators were grouped with the same evaluation criteria, and unnecessary evaluation criteria and evaluation indicators were dropped out. As a result of analyzing the weight of evaluation criteria with the sample of nuclear power experts and the general public, both sides recognized safety as the most important evaluation criterion, and the social factors such as public acceptance appeared to be ranked as more important evaluation criteria by the nuclear energy experts than the general public.

  18. A Statistical Approach for Deriving Key NFC Evaluation Criteria

    International Nuclear Information System (INIS)

    Kim, S. K; Kang, G. B.; Ko, W. I; Young, S. R.; Gao, R. X.

    2014-01-01

    This study suggests 5 evaluation criteria (safety and technology, environmental impact, economic feasibility, social factors, and institutional factors) and 24 evaluation indicators for a NFC (nuclear fuel cycle) derived using factor analysis. To do so, a survey using 1 on 1 interview was given to nuclear energy experts and local residents who live near nuclear power plants. In addition, by conducting a factor analysis, homogeneous evaluation indicators were grouped with the same evaluation criteria, and unnecessary evaluation criteria and evaluation indicators were dropped out. As a result of analyzing the weight of evaluation criteria with the sample of nuclear power experts and the general public, both sides recognized safety as the most important evaluation criterion, and the social factors such as public acceptance appeared to be ranked as more important evaluation criteria by the nuclear energy experts than the general public

  19. Synthesis and antimalarial evaluation of novel isocryptolepine derivatives.

    Science.gov (United States)

    Whittell, Louise R; Batty, Kevin T; Wong, Rina P M; Bolitho, Erin M; Fox, Simon A; Davis, Timothy M E; Murray, Paul E

    2011-12-15

    A series of mono- and di-substituted analogues of isocryptolepine have been synthesized and evaluated for in vitro antimalarial activity against chloroquine sensitive (3D7) and resistant (W2mef) Plasmodium falciparum and for cytotoxicity (3T3 cells). Di-halogenated compounds were the most potent derivatives and 8-bromo-2-chloroisocryptolepine displayed the highest selectivity index (106; the ratio of cytotoxicity (IC(50)=9005 nM) to antimalarial activity (IC(50)=85 nM)). Our evaluation of novel isocryptolepine compounds has demonstrated that di-halogenated derivatives are promising antimalarial lead compounds. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Copper-Catalyzed Synthesis of Trifluoroethylarenes from Benzylic Bromodifluoroacetates.

    Science.gov (United States)

    Ambler, Brett R; Zhu, Lingui; Altman, Ryan A

    2015-08-21

    Trifluoroethylarenes are found in a variety of biologically active molecules, and strategies for accessing this substructure are important for developing therapeutic candidates and biological probes. Trifluoroethylarenes can be directly accessed via nucleophilic trifluoromethylation of benzylic electrophiles; however, current catalytic methods do not effectively transform electron-deficient substrates and heterocycles. To address this gap, we report a Cu-catalyzed decarboxylative trifluoromethylation of benzylic bromodifluoroacetates. To account for the tolerance of sensitive functional groups, we propose an inner-sphere mechanism of decarboxylation.

  1. Benzylation of Toluene over Iron Modified Mesoporous Ceria

    Directory of Open Access Journals (Sweden)

    K.J. Rose Philo

    2012-12-01

    Full Text Available Green chemistry has been looked upon as a sustainable science which accomplishes both economical and environmental goals, simultaneously.With this objective, we developed an alternative process to obtain the industrially important benzyl aromatics by benzylation of aromatics using benzyl chloride, catalysed by mesoporous solid acid catalysts. In this work mesoporous ceria is prepared using neutral surfactant which helped the calcination possible at a lower temperature enabling a higher surface area. Mesoporous ceria modified with Fe can be successfully utilized for the selective benzylation of toluene to more desirable product methyl diphenyl methane with 100% conversion and selectivity in 2 hours using only 50mg of the catalyst under milder condition. The reusability, regenerability, high selectivity, 100% conversion, moderate reaction temperature and absence of solvent, etc. make these catalysts to be used in a truly heterogeneous manner and make the benzylation reaction an environment friendly one. Copyright © 2012 by BCREC UNDIP. All rights reservedReceived: 30th June 2012; Revised: 7th November 2012; Accepted: 10th November 2012[How to Cite: K.J. Rose Philo, S. Sugunan. (2012. Benzylation of Toluene over Iron Modified Mesoporouxs Ceria. Bulletin of Chemical Reaction Engineering & Catalysis, 7(2: 158-164. (doi:10.9767/bcrec.7.2.3759.158-164][How to Link / DOI: http://dx.doi.org/10.9767/bcrec.7.2.3759.158-164 ] | View in 

  2. Influence of gamma irradiation and benzyl adenine on keeping quality of custard apple fruits during storage

    International Nuclear Information System (INIS)

    Chouksey, Swati; Singh, Alpana; Thakur, Rajendra Singh; Deshmukh, Reena

    2013-01-01

    The custard apple (Annona squamosa) fruits were procured from local market, irradiated with radiation doses 0, 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75 kGy and then treated with benzyl adenine (50 and 100 part per million) and stored at ambient temperature (25±5 °C, Relative Humidity 90±2%) for 12 days. The treated fruits were evaluated for sensory (viz; flavour, texture, internal and external colour) and chemical constituents (viz; Total Soluble Solids, titrable acidity, ascorbic acid, free soluble sugar, reducing sugar, non reducing sugar, carbohydrate) during storage. The study concluded that radiation dose of 1.5 kilo Gray along with 50 ppm benzyl adenine enhanced in shelf-life of custard apple fruits by 6 days at ambient temperature with good pulp texture, flavour, colour and nutritional quality as compared to control. (author)

  3. Evaluation of binder and disintegrant properties of starch derived ...

    African Journals Online (AJOL)

    AMARA

    2013-05-15

    May 15, 2013 ... Full Length Research Paper. Evaluation of binder and disintegrant properties of starch derived from Xanthosoma sagittifolium in metronidazole tablets. Onyishi Ikechukwu V., Chime Salome A.* and Ugwu Jonathan C. Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, ...

  4. Evaluation of aerodynamic derivatives from a magnetic balance system

    Science.gov (United States)

    Raghunath, B. S.; Parker, H. M.

    1972-01-01

    The dynamic testing of a model in the University of Virginia cold magnetic balance wind-tunnel facility is expected to consist of measurements of the balance forces and moments, and the observation of the essentially six degree of freedom motion of the model. The aerodynamic derivatives of the model are to be evaluated from these observations. The basic feasibility of extracting aerodynamic information from the observation of a model which is executing transient, complex, multi-degree of freedom motion is demonstrated. It is considered significant that, though the problem treated here involves only linear aerodynamics, the methods used are capable of handling a very large class of aerodynamic nonlinearities. The basic considerations include the effect of noise in the data on the accuracy of the extracted information. Relationships between noise level and the accuracy of the evaluated aerodynamic derivatives are presented.

  5. Radioiodination and biodistribution of NBNPQD ( 2-benzyl-1-oxo-1-2-dihydropyrido (4,3-b) quinoxaline 5,10- dioxide) in tumor bearing mice

    International Nuclear Information System (INIS)

    Ibrahim, I. T.; Habib, S. A.; Wally, H. A.; El-Shishtawy, M. M.

    2012-12-01

    NBNPQD (2-benzyl-1-oxo-1,2 dihydropyrido (quinoxaline 5,10-dioxide) is a new synthesized quinoxaline derivative. It could be labeled with Auger emitter iodine-125 successfully with yield about 90%. The labeled product was evaluated by electrophoresis and studied. 1 23I - NBNPQD was stable up to 48 h post labeling. Biodistribution study of 1 23I - NBNPQD in normal and tumor bearing mice was also conducted. The biodistribution data revealed that 1 23I -NBNPQD diffused rapidly to tumor sites in to both ascites and solid tumor bearing mice. 1 23I -NBNPQD was decline rapidly from most of organs but slowly from tumor sites. In-vitro radiotoxicity of 1 23I - NBNPQD increased with the increase of its radioactivity. This study encourages the possible use of 1 23I - NBNPQD in tumor imaging and treatment. It also encourages further studies on the chemotherapeutic activity of NBNPQD hoping to get a new potent antitumor agent. (Author)

  6. Monte Carlo evaluation of derivative-based global sensitivity measures

    Energy Technology Data Exchange (ETDEWEB)

    Kucherenko, S. [Centre for Process Systems Engineering, Imperial College London, London SW7 2AZ (United Kingdom)], E-mail: s.kucherenko@ic.ac.uk; Rodriguez-Fernandez, M. [Process Engineering Group, Instituto de Investigaciones Marinas, Spanish Council for Scientific Research (C.S.I.C.), C/ Eduardo Cabello, 6, 36208 Vigo (Spain); Pantelides, C.; Shah, N. [Centre for Process Systems Engineering, Imperial College London, London SW7 2AZ (United Kingdom)

    2009-07-15

    A novel approach for evaluation of derivative-based global sensitivity measures (DGSM) is presented. It is compared with the Morris and the Sobol' sensitivity indices methods. It is shown that there is a link between DGSM and Sobol' sensitivity indices. DGSM are very easy to implement and evaluate numerically. The computational time required for numerical evaluation of DGSM is many orders of magnitude lower than that for estimation of the Sobol' sensitivity indices. It is also lower than that for the Morris method. Efficiencies of Monte Carlo (MC) and quasi-Monte Carlo (QMC) sampling methods for calculation of DGSM are compared. It is shown that the superiority of QMC over MC depends on the problem's effective dimension, which can also be estimated using DGSM.

  7. Monte Carlo evaluation of derivative-based global sensitivity measures

    International Nuclear Information System (INIS)

    Kucherenko, S.; Rodriguez-Fernandez, M.; Pantelides, C.; Shah, N.

    2009-01-01

    A novel approach for evaluation of derivative-based global sensitivity measures (DGSM) is presented. It is compared with the Morris and the Sobol' sensitivity indices methods. It is shown that there is a link between DGSM and Sobol' sensitivity indices. DGSM are very easy to implement and evaluate numerically. The computational time required for numerical evaluation of DGSM is many orders of magnitude lower than that for estimation of the Sobol' sensitivity indices. It is also lower than that for the Morris method. Efficiencies of Monte Carlo (MC) and quasi-Monte Carlo (QMC) sampling methods for calculation of DGSM are compared. It is shown that the superiority of QMC over MC depends on the problem's effective dimension, which can also be estimated using DGSM.

  8. Analysis of residual products in benzyl chloride used for the industrial synthesis of quaternary compounds by liquid chromatography with diode-array detection.

    Science.gov (United States)

    Prieto-Blanco, M C; López-Mahía, P; Prada-Rodríguez, D

    2009-02-01

    In industrial and pharmaceutical processes, the study of residual products becomes essential to guarantee the quality of compounds and to eliminate or minimize toxic residual products. Knowledge about the origin of impurities (raw materials, processes, the contamination of industrial plants, etc.) is necessary in preventive treatment and in the control of a product's lifecycle. Benzyl chloride is used as raw material to synthesize several quaternary ammonium compounds, such as benzalkonium chloride, which may have pharmaceutical applications. Benzaldehyde, benzyl alcohol, toluene, chloro derivatives of toluene, and dibenzyl ether are compounds that may be found as impurities in technical benzyl chloride. We proposed a high-performance liquid chromatography method for the separation of these compounds, testing two stationary phases with different dimensions and particle sizes, with the application of photodiode array-detection. The linearity for four possible impurities (benzaldehyde, toluene, alpha,alpha-dichlorotoluene, and 2-chlorotoluene) ranged from 0.1 to 10 microg/mL, limits of detection from 11 to 34 ng/mL, and repeatability from 1% to 2.9% for a 0.3-1.2 microg/mL concentration range. The method was applied to samples of technical benzyl chloride, and alpha,alpha-dichlorotoluene and benzaldehyde were identified by spectral analysis and quantitated. The selection of benzyl chloride with lower levels of impurities is important to guarantee the reduction of residual products in further syntheses.

  9. Synthesis and Analgesic Activity Evaluation of Some Agmatine Derivatives

    Directory of Open Access Journals (Sweden)

    Song Li

    2006-06-01

    Full Text Available A series of N,N’-disubstituted-2-nitroethene-1,1-diamine and N,N’-disubstituted- N’’-cyanoguanidine derivatives were prepared and evaluated for in vivo analgesic activity. The blood brain barrier (BBB VolSurf model was used to predict the BBB permeation profiles of our synthesized compounds. Some compounds show both remarkable analgesic activity and good BBB permeation profiles, and these compounds might be developed for treatment of opioid tolerance and dependence.

  10. Evaluation of substituted ebselen derivatives as potential trypanocidal agents.

    Science.gov (United States)

    Gordhan, Heeren M; Patrick, Stephen L; Swasy, Maria I; Hackler, Amber L; Anayee, Mark; Golden, Jennifer E; Morris, James C; Whitehead, Daniel C

    2017-02-01

    Human African trypanosomiasis is a disease of sub-Saharan Africa, where millions are at risk for the illness. The disease, commonly referred to as African sleeping sickness, is caused by an infection by the eukaryotic pathogen, Trypanosoma brucei. Previously, a target-based high throughput screen revealed ebselen (EbSe), and its sulfur analog, EbS, to be potent in vitro inhibitors of the T. brucei hexokinase 1 (TbHK1). These molecules also exhibited potent trypanocidal activity in vivo. In this manuscript, we synthesized a series of sixteen EbSe and EbS derivatives bearing electron-withdrawing carboxylic acid and methyl ester functional groups, and evaluated the influence of these substituents on the biological efficacy of the parent scaffold. With the exception of one methyl ester derivative, these modifications ablated or blunted the potent TbHK1 inhibition of the parent scaffold. Nonetheless, a few of the methyl ester derivatives still exhibited trypanocidal effects with single-digit micromolar or high nanomolar EC 50 values. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Field ion emission from tungsten wires covered with organic micro needles of benzyl nitrile

    International Nuclear Information System (INIS)

    Helal, A.I.; Zahran, N.F.

    1986-01-01

    Benzyl nitrile micro needles are grown on the surface of a 10 um tungsten wire. The activated wires are used as field anodes in field ionization source. The activation time using benzyl nitrile as an activator is much shorter than the corresponding time required for benzo nitrile activation. Field ionization mass spectra of benzo- and benzyl-nitriles are measured by the new emitters

  12. catalysed selective oxidation of benzyl alcohols using TEMPO and ...

    Indian Academy of Sciences (India)

    A general scheme for the oxidation of benzyl alcohols catalyzed by silica functionalized copper (II) has been designed. TEMPO, a free radical, assists this oxidation that was initiated by molecular oxygen which converts it to a primary oxidant. This catalytic combination i.e. SiO2 -Cu(II) in presence of TEMPO and oxygen ...

  13. Selective oxidation of benzyl alcohol with tert-butylhydroperoxide ...

    Indian Academy of Sciences (India)

    the solvent and in this case, acetonitrile gives the best conversion results. The kinetic of ... Experimental. 2.1 Materials ... Subsequently, the products were filtered, washed thoroughly ..... mesh; benzyl alcohol 30 mmol; TBHP 30 mmol; 15 ml ace- tonitrile ... vent was changed for each run while the other condi- tions, (0.2 g of ...

  14. Rapid field multiplication of plantains using benzyl adenine or ...

    African Journals Online (AJOL)

    Une technique appropriee et moins chere pour la multiplication rapide sur Ie terrain de deux varietes locales de plantain Apantu (une corne fausse) et Asamienu (une come veritable) a ete obtenue par injection de 6 ou 8 ml du jus de noix de coco mur sec apres L' ebullition et la filtration ou de 4 ml 10-2 M benzyle adenine ...

  15. Nuclear magnetic resonance of D(-)-α-amino-benzyl penicillin

    International Nuclear Information System (INIS)

    Aguiar, Monica R.M.P.; Gemal, Andre L.; San Gil, Rosane A.S.; Menezes, Sonia M.C.

    1995-01-01

    The development of new drugs from penicillins has induced the study of this substances by nuclear magnetic resonance. Several samples of D(-)-α-amino-benzyl penicillin were analysed using 13 C NMR techniques in aqueous solution and solid state. Spectral data of this compounds were shown and the results were presented and analysed

  16. Experimental and theoretical investigation of benzyl-N ...

    Indian Academy of Sciences (India)

    Experimental and theoretical investigation of benzyl-N-pyrrolylketene, one- step procedure for preparing of new β-lactams by [2+2] cycloaddition reaction. MASOUMEH BEHZADI, KAZEM SAIDI. ∗. , MOHAMMAD REZA ISLAMI and. HOJATOLLAH KHABAZZADEH. Department of Chemistry, Shahid Bahonar University of ...

  17. Evaluation of antituberculosis activity and DFT study on dipyrromethane-derived hydrazone derivatives

    Science.gov (United States)

    Rawat, Poonam; Singh, R. N.; Niranjan, Priydarshni; Ranjan, Alok; Holguín, Norma Rosario Flores

    2017-12-01

    This paper evaluates the anti-tubercular activity of dipyrromethane-derived hydrazones derivatives (3a-d) against strain of Mycobacterium tuberculosis H37Rv. The newly synthesized compounds have been obtained in good yield based on the condensation of aromatic aldehyde derivatives with pyrrole hydrazone in presence of catalyst and well characterized with spectroscopic methods (1H, 13C NMR, Mass spectrometry) and elemental analysis. The singlet observed in the experimental 1H and 13C NMR spectra in the range of 5.3-5.7 ppm and 30-33.86 ppm, respectively, indicating that two pyrrole units are joined at meso position. The electronic transitions observed in the experimental spectra are n→π* and π →π* in nature. Experimental and theoretical findings corroborate well with each other. The substitution of acceptor group (-NO2) at ortho- and meta-positions of benzene ring, present at meso-position of dipyrromethane is responsible for variation in β0 values. The calculated NLO of (3a-d) are much greater than those of p-nitroaniline (PNA). The solvent induced effects on the non-linear optical properties were studied and found to enhance NLO properties of the molecules as dielectric constants of the solvents increases. On the basis of results it is anticipated that these dipyrromethanes will be useful for both antimicrobial and non-linear optical (NLO) applications. With the help of Microplate Alamar Blue assay (MABA) method all (3a-d) compounds were screened for their anti-tubercular activity and found that 3b and 3d have higher inhibitory activity against strain of M. tuberculosis H37Rv.

  18. Syntheses and anti-microbial evaluation of new quinoline scaffold derived pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Shikha S. Dave

    2016-09-01

    Full Text Available A series of diversely substituted chalcones derived from a quinoline scaffold, e.g. (E-3-(2-chloroquinolin-3-yl-1-(2-hydroxyphenyl prop-2-en-1-one and its pyrimidine analogues e.g. 2-[2-amino-6-(2-chloroquinolin-3-yl-5,6-dihydropyrimidin-4-yl]phenols have been prepared by condensation of 2-chloro-3-formyl quinoline with differently substituted 2-hydroxy acetophenones and further treatment with guanidine carbonate. All the newly synthesized compounds have been evaluated for their in vitro growth inhibitory activity against Escherichia coli, Pseudomonas vulgaris, Bacillus subtilis, Staphylococcus aureus, Staphylococcus typhi, Candida albicans, Aspergillus niger and Pseudomonas chrysogenum.

  19. In situ activation of benzyl alcohols with XtalFluor-E: formation of 1,1-diarylmethanes and 1,1,1-triarylmethanes through Friedel-Crafts benzylation.

    Science.gov (United States)

    Desroches, Justine; Champagne, Pier Alexandre; Benhassine, Yasmine; Paquin, Jean-François

    2015-02-28

    The Friedel-Crafts benzylation of arenes using benzyl alcohols activated in situ with XtalFluor-E is described. A wide range of 1,1-diarylmethanes and 1,1,1-triarylmethanes were prepared under experimentally simple and mild conditions, without the need for a transition metal or a strong Lewis acid. Notably, the reactivity observed demonstrates the potential of XtalFluor-E to induce C-OH bond ionization and SN1 reactivity of benzylic alcohols.

  20. Synthesis, spectroscopic characterization and pharmacological evaluation of oxazolone derivatives

    Directory of Open Access Journals (Sweden)

    Fareed Ghulam

    2013-01-01

    Full Text Available A series of 4-aryl methylidene-2-phenyl/methyl-5-(4H-oxazolone derivatives (2-7 have been synthesized using the reported method by condensation of aldehydes with N-benzoyl / N-acetyl glycine in the presence of zinc oxide as a catalyst and acetic anhydride at room temperature in ethanol. The compounds (2-6 are new derivatives. The structures of compounds were evaluated on the basis of 1H-NMR, 13C-NMR, EIMS, FT-IR and elemental analysis. All the compounds were screened for their antibacterial and urease inhibition activity. Antibacterial activity was tested by agar well diffusion method using Mueller Hinton Agar medium. Compound (2 showed excellent activity against S. aureus which has 16 mm (80% inhibition and above 24 mm (70% against S. typhi. The most active compound against E. coli was compound (6 having 20 mm (80% inhibition followed by compound (5 having above 18 mm (70% inhibition. Urease inhibition activity of all the compounds was determined by indophenol method. Compounds (3, 6 and (7 showed significant inhibition against Jacks bean urease.

  1. On the role of resonantly stabilized radicals in polycyclic aromatic hydrocarbon (PAH) formation: pyrene and fluoranthene formation from benzyl-indenyl addition.

    Science.gov (United States)

    Sinha, Sourab; Rahman, Ramees K; Raj, Abhijeet

    2017-07-26

    Resonantly stabilized radicals, such as propargyl, cyclopentadienyl, benzyl, and indenyl, play a vital role in the formation and growth of polycyclic aromatic hydrocarbons (PAHs) that are soot precursors in engines and flames. Pyrene is considered to be an important PAH, as it is thought to nucleate soot particles, but its formation pathways are not well known. This paper presents a reaction mechanism for the formation of four-ring aromatics, pyrene and fluoranthene, through the combination of benzyl and indenyl radicals. The intermediate species and transition structures involved in the elementary reactions of the mechanism were studied using density functional theory, and the reaction kinetics were evaluated using transition state theory. The barrierless addition of benzyl and indenyl to form the adduct, 1-benzyl-1H-indene, was found to be exothermic with a reaction energy of 204.2 kJ mol -1 . The decomposition of this adduct through H-abstraction and H 2 -loss was studied to determine the possible products. The rate-of-production analysis was conducted to determine the most favourable reactions for pyrene and fluoranthene formation. The premixed laminar flames of toluene, ethylbenzene, and benzene were simulated using a well-validated hydrocarbon fuel mechanism with detailed PAH chemistry after adding the proposed reactions to it. The computed and experimentally observed species profiles were compared to determine the effect of the new reactions for pyrene and fluoranthene formation on their concentration profiles. The role of benzyl and indenyl combination in PAH formation and growth is highlighted.

  2. Toxicological evaluation of clay minerals and derived nanocomposites: a review.

    Science.gov (United States)

    Maisanaba, Sara; Pichardo, Silvia; Puerto, María; Gutiérrez-Praena, Daniel; Cameán, Ana M; Jos, Angeles

    2015-04-01

    Clays and clay minerals are widely used in many facets of our society. This review addresses the main clays of each phyllosilicate groups, namely, kaolinite, montmorillonite (Mt) and sepiolite, placing special emphasis on Mt and kaolinite, which are the clays that are more frequently used in food packaging, one of the applications that are currently exhibiting higher development. The improvements in the composite materials obtained from clays and polymeric matrices are remarkable and well known, but the potential toxicological effects of unmodified or modified clay minerals and derived nanocomposites are currently being investigated with increased interest. In this sense, this work focused on a review of the published reports related to the analysis of the toxicological profile of commercial and novel modified clays and derived nanocomposites. An exhaustive review of the main in vitro and in vivo toxicological studies, antimicrobial activity assessments, and the human and environmental impacts of clays and derived nanocomposites was performed. From the analysis of the scientific literature different conclusions can be derived. Thus, in vitro studies suggest that clays in general induce cytotoxicity (with dependence on the clay, concentration, experimental system, etc.) with different underlying mechanisms such as necrosis/apoptosis, oxidative stress or genotoxicity. However, most of in vivo experiments performed in rodents showed no clear evidences of systemic toxicity even at doses of 5000mg/kg. Regarding to humans, pulmonary exposure is the most frequent, and although clays are usually mixed with other minerals, they have been reported to induce pneumoconiosis per se. Oral exposure is also common both intentionally and unintentionally. Although they do not show a high toxicity through this pathway, toxic effects could be induced due to the increased or reduced exposure to mineral elements. Finally, there are few studies about the effects of clay minerals on

  3. Synthesis and anticancer evaluation of imidazolinone and benzoxazole derivatives

    Directory of Open Access Journals (Sweden)

    Heba A. El-Hady

    2017-05-01

    Full Text Available A series of imidazolinone and benzoxazole derivatives (3 and 5 have been synthesized by the condensation of oxazolinone derivatives (2a–c with aniline and 2-hydroxyaniline. Acetyl derivatives (4, 6 and 7 were prepared via acetylation of compounds 3 and 5 with acetic anhydride and chloroacetyl chloride. The results revealed that imidazolinone and benzoxazole derivatives are potent against the cancer cell lines MCF-7 and HePG2. In particular, benzoxazole derivatives are more potent than imidazolinone derivatives.

  4. Synthesis and evaluation of the antiplasmodial activity of tryptanthrin derivatives

    Directory of Open Access Journals (Sweden)

    Liliane Abodo Onambele

    2015-08-01

    Full Text Available Malaria remains one of the most deadly diseases threatening humankind and is still affecting a significant proportion of the world population, especially in Africa. Chemotherapy is a vital component of the fight against the disease and new antimalarial agents are urgently needed to curb the spread of malaria parasites that are resistant to existing drugs. The natural product tryptanthrin is known for its wide range of activities, including antiplasmodial activity, but its poor solubility has undermined its development as potent antimicrobial and antiprotozoan agent. The aim of this work was to synthesize analogues of tryptanthrin and to evaluate their antiplasmodial activity against the asexual and sexual blood stages of Plasmodium falciparum. Our results suggest that most tryptanthrin analogues retained their antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant malaria parasites in the nanomolar range (30–100 nM. The antiplasmodial activity of the most active compound NT1 (IC50: 30 nM; SI: 155.9 was similar in both strains and close to that of chloroquine (IC50: 20 nM on the sensitive strain. The antiplasmodial activity was improved with derivatization, thus pointing out the necessity to explore tryptanthrin using medicinal chemistry approaches. Ten (10 of the tested derivatives met the criteria, allowing for advancement to animal testing, i.e., SI > 100 and IC50 < 100 nM. In addition to their activity on the asexual stages, tryptanthrin and two selected derivatives (NT1 and T8 prevented the maturation of gametocytes at their IC90 concentrations, indicating a transmission-blocking potential. Moreover, NT1 was able to impair gametogenesis by reducing the exflagellation of microgametes by 20% at IC90, while tryptanthrin and T8 had no influence on exflagellation. The results of this study confirm that tryptanthrin and its derivatives are potential antimalarial candidates with abilities to kill the

  5. Synthesis and cytotoxicity evaluation of thiosemicarbazones and their thiazole derivatives

    Directory of Open Access Journals (Sweden)

    Saulo Feheiberg Pinto Braga

    Full Text Available ABSTRACT The aims of this study were to synthesize a series of thiosemicarbazones and their thiazole derivatives, to investigate their cytotoxic activity against three human cancers and normal (Vero cells cell lines, and to evaluate the pro-apoptotic potential of the most active compounds. Materials and Methods: The thiosemicarbazones were obtained by reacting an aromatic aldehyde with thiosemicarbazide (yield 71-96%, which were subjected to a cyclization with α-bromoacetophenone to yield the required thiazole heterocycles (yield 63-100%. All the synthesized compounds were screened at 50 µM concentration against three cell lines representing HL60 (promyelocytic leukemia, Jurkat (acute lymphoblastic leukemia, and MCF-7 (breast cancer. The pro-apoptotic effect was measured by flow cytometry as the percentage of cells with hypodiploid DNA. Results: Three thiazole compounds showed activity against at least one tumor cell line (IC50 = 43-76 µM and low cytotoxicity against Vero cells (IC50 > 100 M. The most active compound of this series induced 91% and 51% DNA fragmentation in HL60 and MCF-7 cell lines, respectively, suggesting that this compound triggered apoptosis in these cells. Conclusion: Among the synthesized compounds, one in particular was found to exert antiproliferative and pro-apoptotic activity on tumor cells and can be considered promising as a lead molecule for the design of new analogues with improved activity.

  6. Studies on Synthesis of Pyrimidine Derivatives and their Pharmacological Evaluation

    Directory of Open Access Journals (Sweden)

    T. A. Naik

    2007-01-01

    Full Text Available 1,3,4-Oxadiazoles were associated with broad spectrum of biological activities including antituberculosis, anticonvulsant, anti-inflammatory, insecticidal, antifungal, analgesic and antitumor properties. Morpholine derivatives find their wide spectrum of antimicrobial activity and exhibit anthelmintic, bactericidal and insecticidal activity. Pyrimidine derivatives are also reported to possess antibacterial, antimicrobial, antifungal, anticancer and anticonvulsant activities. Encouraged by this observations we decided to synthesised novel pyrimidine derivatives.

  7. Benzyl alcohol increases voluntary ethanol drinking in rats.

    Science.gov (United States)

    Etelälahti, T J; Eriksson, C J P

    2014-09-01

    The anabolic steroid nandrolone decanoate has been reported to increase voluntary ethanol intake in Wistar rats. In recent experiments we received opposite results, with decreased voluntary ethanol intake in both high drinking AA and low drinking Wistar rats after nandrolone treatment. The difference between the two studies was that we used pure nandrolone decanoate in oil, whereas in the previous study the nandrolone product Deca-Durabolin containing benzyl alcohol (BA) was used. The aims of the present study were to clarify whether the BA treatment could promote ethanol drinking and to assess the role of the hypothalamic-pituitary-adrenal-gonadal axes (HPAGA) in the potential BA effect. Male AA and Wistar rats received subcutaneously BA or vehicle oil for 14 days. Hereafter followed a 1-week washout and consecutively a 3-week voluntary alcohol consumption period. The median (± median absolute deviation) voluntary ethanol consumption during the drinking period was higher in BA-treated than in control rats (4.94 ± 1.31 g/kg/day vs. 4.17 ± 0.31 g/kg/day, p = 0.07 and 1.01 ± 0.26 g/kg/day vs. 0.38 ± 0.27 g/kg/day, p = 0.05, for AA and Wistar rats, respectively; combined effect p < 0.01). The present results can explain the previous discrepancy between the two nandrolone studies. No significant BA effects on basal and ethanol-mediated serum testosterone and corticosterone levels were observed in blood samples taken at days 1, 8 and 22. However, 2h after ethanol administration significantly (p = 0.02) higher frequency of testosterone elevations was detected in high drinking AA rats compared to low drinking Wistars, which supports our previous hypotheses of a role of testosterone elevation in promoting ethanol drinking. Skin irritation and dermatitis were shown exclusively in the BA-treated animals. Altogether, the present results indicate that earlier findings obtained with Deca-Durabolin containing BA need to be re-evaluated. Copyright © 2014 Elsevier Inc. All

  8. Antinociceptive, anti-inflammatory and toxicological evaluation of semi-synthetic molecules obtained from a benzyl-isothiocyanate isolated from Moringa oleifera Lam. in a temporomandibular joint inflammatory hypernociception model in rats.

    Science.gov (United States)

    Dos Santos, Alain Oliveira; do Val, Danielle Rocha; da Silveira, Felipe Dantas; Gomes, Francisco Isaac Fernandes; Freitas, Hermany Capistrano; de Assis, Ellen Lima; de Almeida, Diana Kelly Castro; da Silva, Igor Iuco Castro; Barbosa, Francisco Geraldo; Mafezoli, Jair; da Silva, Marcos Reinaldo; de Castro Brito, Gerly Anne; Clemente-Napimoga, Juliana Trindade; de Paulo Teixera Pinto, Vicente de Paulo Teixeira; Filho, Gerardo Cristino; Bezerra, Mirna Marques; Chaves, Hellíada Vasconcelos

    2018-02-01

    Inflammation is a key component of many clinical conditions that affect the temporomandibular joint (TMJ) and Moringa oleifera Lam. has been used to treat inflammatory diseases. Here, we evaluated the toxicological effects on mice of a naturally-occurring isothiocyanate from M. oleifera and its seven analogue molecules. Further, the anti-nociceptive and anti-inflammatory effects on a rat model of TMJ inflammatory hypernociception were assessed. The systemic toxicological profile was determined in mice over a 14-day period: MC-1 1 μg/kg; MC-D1 1 μg/kg, MC-D3 100 μg/kg, MC-D6 1 μg/kg, MC-D7 1 μg/kg, MC-D8 1 μg/kg, MC-D9 10 μg/kg, and MC-H 1 μg/kg. The safest molecules were assayed for anti-nociceptive efficacy in the formalin (1.5%, 50 μL) and serotonin (255 mg) induced TMJ inflammatory hypernociception tests. The anti-inflammatory effect was evaluated through the vascular permeability assay using Evans blue. Further, the rota-rod test evaluated any motor impairment. Among the tested molecules, MC-D7, MC-D9, and MC-H were not toxic at the survival rate test, biochemical, and hystological analysis. They reduced the formalin-induced TMJ inflammatory hypernociception, but only MC-H decreased the serotonin-induced TMJ inflammation, suggesting an adrenergic receptor-dependent effect. They diminished the plasmatic extravasation, showing anti-inflammatory activity. At the rota-rod test, no difference was observed in comparison with control groups, reinforcing the hypothesis of anti-nociceptive effetc without motor impairment in animals. The analogues MC-D7, MC-D9, and MC-H were safe at the tested doses and efficient in reducing the formalin-induced TMJ hypernociception in rats. Our next steps include determining their mechanisms of anti-nociceptive action. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Influence of gamma irradiation and benzyl adenine on keeping quality of custard apple fruits during storage.

    Science.gov (United States)

    Chouksey, Swati; Singh, Alpana; Thakur, Rajendra Singh; Deshmukh, Reena

    2013-10-01

    The custard apple (Annona squamosa) fruits were procured from local market, irradiated with radiation doses 0, 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75 kGy and then treated with benzyl adenine (50 and 100 part per million) and stored at ambient temperature (25 ± 5 °C, Relative Humidity 90 ± 2%) for 12 days. The treated fruits were evaluated for sensory (viz; flavour, texture, internal and external colour) and chemical constituents (viz; Total Soluble Solids, titrable acidity, ascorbic acid, free soluble sugar, reducing sugar. non reducing sugar, carbohydrate) during storage. The study concluded that radiation dose of 1.5 kilo Gray along with 50 ppm benzyl adenine enhanced in shelf-life of custard apple fruits by 6 days at ambient temperature with good pulp texture, flavour, colour and nutritional quality as compared to control.

  10. Evaluation of satellite derived spectral diffuse attenuation coefficients

    Digital Repository Service at National Institute of Oceanography (India)

    Suresh, T.; Talaulikar, M.; Desa, E.; Mascarenhas, A.A.M.Q.; Matondkar, S.G.P.

    , 443, 490, 510, 555 and 670 nm derived from the ocean color satellite sensor, SeaWiFS with the in-situ measured values from the Arabian Sea is compared. The satellite derived values are found to be comparable to the measured values in the lower...

  11. In vitro and in vivo trypanocidal evaluation of nickel complexes with an azapurine derivative against Trypanosoma cruzi.

    Science.gov (United States)

    Maldonado, Carmen R; Marín, Clotilde; Olmo, Francisco; Huertas, Oscar; Quirós, Miguel; Sánchez-Moreno, Manuel; Rosales, María J; Salas, Juan M

    2010-10-14

    Seven ternary nickel(II) complexes (three previously described and four firstly described here) with an azapurine derivative (the anionic form of 4,6-dimethyl-1,2,3-triazolo[4,5-d]pyrimidin-5,7-dione) have been synthesized and spectroscopically characterized, and the crystal structures of three of them have been solved by X-ray diffraction. Studies in vitro and in vivo on the antiproliferative activity of these complexes against Trypanosoma cruzi (epimastigote, amastigote, and trypomastigote forms) have been carried out, displaying in some cases significantly higher antitrypanosomatid activity and lower toxicity than the reference drug for Chagas' disease, benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide). Ultrastructural analysis and metabolism excretion studies were also executed in order to propose a possible mechanism of action for the assayed drugs.

  12. 17O NMR parameters of some substituted benzyl ethers components: Ab initio study

    Directory of Open Access Journals (Sweden)

    Mahdi Rezaei Sameti

    2016-09-01

    Full Text Available The 17O NMR chemical shielding tensors and chemical shift for a set of substituted benzyl ethers derivatives containing (methyl, ethyl, isopropyl, t-butyl, brome and lithium have been calculated. The molecular structures were fully optimized using B3LYP/6-31G(d,p. The calculation of the 17O shielding tensors employed the GAUSSIAN 98 implementation of the gauge-including atomic orbital (GIAO and continuous set of gauge transformations (CSGT by using 6-31G (d,p, 6-31++G(d,p and 6-311++G(d,p basis set methods at density functional levels of theories (DFT. The values determined using the GIAO and CSGT were found to give a good agreement with the experimental chemical shielding.

  13. Synthesis and Biological Evaluation of Resveratrol Derivatives as Melanogenesis Inhibitors

    Directory of Open Access Journals (Sweden)

    Qing Liu

    2015-09-01

    Full Text Available Resveratrol (1, a naturally occurring stilbene compound, has been suggested as a potential whitening agent with strong inhibitory activity on melanin synthesis. However, the use of resveratrol in cosmetics has been limited due to its chemical instability and poor bioavailability. Therefore, resveratrol derivatives were prepared to improve bioavailability and anti-melanogenesis activity. Nine resveratrol derivatives including five alkyl ether derivatives with C2H5, C4H9, C5H11, C6H13, and C8H17 (2a–2e and four ester derivatives with CH3, CH=C(CH32, CH(C2H5C4H9, C7H15 (3a–3d were newly synthesized and their effect on melanin synthesis were assessed. All the synthetic derivatives efficiently reduced the melanin content in α-MSH stimulated B16F10 melanoma cells. Further investigation showed that the inhibitory effect of 2a on melanin synthesis was achieved not by the inhibition of tyrosinase activity but by the inhibition of melanogenic enzyme expressions such as tyrosinase and tyrosinase-related protein (TRP-1. Our synthetic resveratrol derivatives have more lipophilic properties than resveratrol by the addition of alkyl or acyl chains to free hydroxyl moiety of resveratrol; thus, they are expected to show better bioavailability in skin application. Therefore, we suggest that our synthetic resveratrol derivatives might be promising candidates for better practical application to skin-whitening cosmetics.

  14. A novel serotonin transporter ligand: (5-Iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, Z.-P.; Choi, S.-R.; Hou, Catherine; Mu Mu; Kung, M.-P. E-mail: kunghf@sunmac.spect.upenn.edu; Acton, Paul D.; Kung, Hank F

    2000-02-01

    The serotonin transporters (SERT) are the primary binding sites for selective serotonin reuptake inhibitors, commonly used antidepressants such as fluoxetine, sertraline, and paroxetine. Imaging of SERT with positron emission tomography and single photon emission computed tomography in humans would provide a useful tool for understanding how alterations of this system are related to depressive illnesses and other psychiatric disorders. In this article the synthesis and characterization of [{sup 125}I]ODAM [(5-iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol, 9)] as an imaging agent in the evaluation of central nervous system SERT are reported. A new reaction scheme was developed for the preparation of compound 9, ODAM, and the corresponding tri-n-butyltin derivative 10. Upon reacting 10 with hydrogen peroxide and sodium[{sup 125}I]iodide, the radiolabeled [{sup 125}I]9 was obtained in good yield (94% yield, radiochemical purity >95%). In an initial binding study using cortical membrane homogenates of rat brain, ODAM displayed a good binding affinity with a value of K{sub i}=2.8{+-}0.88 nM. Using LLC-PK{sub 1} cells specifically expressing the individual transporter (i.e. dopamine [DAT], norepinephrine [NET], and SERT, respectively), ODAM showed a strong inhibition on SERT (K{sub i}=0.12{+-}0.02 nM). Inhibition constants for the other two transporters were lower (K{sub i}=3.9{+-}0.7 {mu}M and 20.0 {+-} 1.9 nM for DAT and NET, respectively). Initial biodistribution study in rats after an intravenous (IV) injection of [{sup 125}I]ODAM showed a rapid brain uptake and washout (2.03, 1.49, 0.79, 0.27, and 0.07% dose/organ at 2, 30, 60, 120, and 240 min, respectively). The hypothalamus region where the serotonin neurons are located exhibited a high specific uptake. Ratios of hypothalamus-cerebellum/cerebellum based on percent dose per gram of these two regions showed values of 0.35, 0.86, 0.86, 0.63, and 0.34 at 2, 30, 60, 120, and 240 min, post-IV injection

  15. A novel serotonin transporter ligand: (5-Iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol

    International Nuclear Information System (INIS)

    Zhuang, Z.-P.; Choi, S.-R.; Hou, Catherine; Mu Mu; Kung, M.-P.; Acton, Paul D.; Kung, Hank F.

    2000-01-01

    The serotonin transporters (SERT) are the primary binding sites for selective serotonin reuptake inhibitors, commonly used antidepressants such as fluoxetine, sertraline, and paroxetine. Imaging of SERT with positron emission tomography and single photon emission computed tomography in humans would provide a useful tool for understanding how alterations of this system are related to depressive illnesses and other psychiatric disorders. In this article the synthesis and characterization of [ 125 I]ODAM [(5-iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol, 9)] as an imaging agent in the evaluation of central nervous system SERT are reported. A new reaction scheme was developed for the preparation of compound 9, ODAM, and the corresponding tri-n-butyltin derivative 10. Upon reacting 10 with hydrogen peroxide and sodium[ 125 I]iodide, the radiolabeled [ 125 I]9 was obtained in good yield (94% yield, radiochemical purity >95%). In an initial binding study using cortical membrane homogenates of rat brain, ODAM displayed a good binding affinity with a value of K i =2.8±0.88 nM. Using LLC-PK 1 cells specifically expressing the individual transporter (i.e. dopamine [DAT], norepinephrine [NET], and SERT, respectively), ODAM showed a strong inhibition on SERT (K i =0.12±0.02 nM). Inhibition constants for the other two transporters were lower (K i =3.9±0.7 μM and 20.0 ± 1.9 nM for DAT and NET, respectively). Initial biodistribution study in rats after an intravenous (IV) injection of [ 125 I]ODAM showed a rapid brain uptake and washout (2.03, 1.49, 0.79, 0.27, and 0.07% dose/organ at 2, 30, 60, 120, and 240 min, respectively). The hypothalamus region where the serotonin neurons are located exhibited a high specific uptake. Ratios of hypothalamus-cerebellum/cerebellum based on percent dose per gram of these two regions showed values of 0.35, 0.86, 0.86, 0.63, and 0.34 at 2, 30, 60, 120, and 240 min, post-IV injection, respectively. The specific uptake in hypothalamus

  16. Selective methylation of kaempferol via benzylation and deacetylation of kaempferol acetates

    OpenAIRE

    Mei, Qinggang; Wang, Chun; Yuan, Weicheng; Zhang, Guolin

    2015-01-01

    A strategy for selective mono-, di- and tri-O-methylation of kaempferol, predominantly on the basis of selective benzylation and controllable deacetylation of kaempferol acetates, was developed. From the selective deacetylation and benzylation of kaempferol tetraacetate (1), 3,4′,5,-tri-O-acetylkaempferol (2) and 7-O-benzyl-3,4′5,-tri-O-acetylkaempferol (8) were obtained, respectively. By controllable deacetylation and followed selective or direct methylation of these two intermediates, eight...

  17. EVALUATION OF NEEM (AZADIRACHTA IND/CA) DERIVATIVES ...

    African Journals Online (AJOL)

    The list continues to expand, as neem derivatives are tested ..... various stages stem borers and best integration of various management options are necessary. ... This may be an additional line of future neem study in the field of insecticides.

  18. Synthesis and biological evaluation of 2-substituted benzimidazole derivatives

    Directory of Open Access Journals (Sweden)

    Gurusamy Mariappan

    2015-09-01

    Full Text Available A novel series of 2-substituted benzimidazole derivatives (3a–3j were synthesized by the reaction of 2-chloro methyl benzimidazole with substituted primary aromatic amines. All the compounds were characterized by UV, IR, 1H NMR, mass spectral data and CHN elemental analysis. The synthesized derivatives were screened for analgesic and anti-inflammatory activities. All the compounds showed significant effect at 100 mg/kg p.o. and the experimental data are statistically significant at p < 0.01 level.

  19. 1-Benzyl-3-methylquinoxalin-2(1H-one

    Directory of Open Access Journals (Sweden)

    Youssef Ramli

    2018-03-01

    Full Text Available The asymmetric unit of the title compound, C16H14N2O, contains three independent molecules differing primarily in the orientations of the benzyl groups. Each independent molecule forms inversion related dimers via offset π-stacking interactions. For two of these dimers, stacks are formed approximately along the a-axis direction by a combinations of C—H...N and C—H...π(ring contacts, in addition to the offset π-stacking interactions. The third set of dimers are also stacked in the same direction but only by pairwise C—H...N hydrogen bonds.

  20. Evaluation of Oryza sativa x O. glaberrima derived progenies for ...

    African Journals Online (AJOL)

    USER

    2010-06-28

    Jun 28, 2010 ... The genus Oryza has two cultivated species, Asian rice (Oryza sativa L.) and African rice (Oryza glaberrima Steud.) and 22 wild species. O. glaberrima is low yielding but has useful genes for resistance to biotic and abiotic stresses. Introgression lines derived from backcrossing of O. sativa x O. glaberrima,.

  1. Synthesis and biological evaluation of vinylogous combretastatin A-4 derivatives.

    Science.gov (United States)

    Kaffy, Julia; Pontikis, Renée; Florent, Jean-Claude; Monneret, Claude

    2005-07-21

    Stereospecific syntheses of the Z-E and E-Z vinylogues of combretastatin A-4, and two B-ring related analogues, were achieved through a Suzuki-Miyaura coupling. As compared to CA4, the derivative with a phenyl moiety has shown increased potency in its ability to inhibit tubulin polymerisation.

  2. Synthesis and Biological Activity Evaluation of Novel Heterocyclic Pleuromutilin Derivatives

    Directory of Open Access Journals (Sweden)

    Yunpeng Yi

    2017-06-01

    Full Text Available A series of pleuromutilin derivatives were synthesized by two synthetic procedures under mild reaction conditions and characterized by Nuclear Magnetic Resonance (NMR, Infrared Spectroscopy (IR, and High Resolution Mass Spectrometer (HRMS. Most of the derivatives with heterocyclic groups at the C-14 side of pleuromutilin exhibited excellent in vitro antibacterial activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA, methicillin-resistant Staphylococcus epidermidis (MRSE, and vancomycin-resistant Enterococcus (VRE in vitro antibacterial activity. The synthesized derivatives which contained pyrimidine rings, 3a, 3b, and 3f, displayed modest antibacterial activities. Compound 3a, the most active antibacterial agent, displayed rapid bactericidal activity and affected bacterial growth in the same manner as that of tiamulin fumarate. Moreover, molecular docking studies of 3a and lefamulin provided similar information about the interactions between the compounds and 50S ribosomal subunit. The results of the study show that pyrimidine rings should be considered in the drug design of pleuromutilin derivatives.

  3. Synthesis and anticancer evaluation of (-1)- aretigenin derivatives

    International Nuclear Information System (INIS)

    Xu, Y.; Chen, G.

    2014-01-01

    Seven (-)-arctigenin derivatives 1-7 were designed and synthesized by using Mannich and acylation methods to improve the activity and bioavailability of (-)-arctigenin. Structures of compounds 1-7 were elucidated on the basis of spectroscopic analysis and chemical evidence. Anticancer activity of these compounds on SGC7901 was assayed in vitro. (author)

  4. Synthesis and anticancer evaluation of (-1)- aretigenin derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Y.; Chen, G. [Liaoning Univ. of Traditional Chinese Medicine, Dalian (China)

    2014-10-15

    Seven (-)-arctigenin derivatives 1-7 were designed and synthesized by using Mannich and acylation methods to improve the activity and bioavailability of (-)-arctigenin. Structures of compounds 1-7 were elucidated on the basis of spectroscopic analysis and chemical evidence. Anticancer activity of these compounds on SGC7901 was assayed in vitro. (author)

  5. A STATISTICAL APPROACH FOR DERIVING KEY NFC EVALUATION CRITERIA

    Directory of Open Access Journals (Sweden)

    S.K. KIM

    2014-02-01

    As a result of analyzing the weight of evaluation criteria with the sample of nuclear power experts and the general public, both sides recognized safety as the most important evaluation criterion, and the social factors such as public acceptance appeared to be ranked as more important evaluation criteria by the nuclear energy experts than the general public.

  6. Synthesis and evaluation of antimalarial activity of curcumin derivatives

    International Nuclear Information System (INIS)

    Gomes, Patricia Ramos; Miguel, Fabio Balbino; Almeida, Mauro Vieira de; Couri, Mara Rubia Costa; Oliveira, Michael Eder de; Ferreira, Vanessa Viana; Guimaraes, Daniel Silqueira Martins; Lima, Aline Brito de; Barbosa, Camila de Souza; Oliveira, Mariana Amorim de; Almeida, Mauro Vieira de; Viana, Gustavo Henrique Ribeiro; Varotti, Fernando de Pilla

    2014-01-01

    ne of the main challenges in the development of new antimalarial drugs is to achieve a viable lead candidate with good pharmacokinetic properties. Curcumin has a broad range of biological activities, including antimalarial activity. Herein, we report the antimalarial activity of six curcumin derivatives (6-12) and an initial analysis of their pharmacokinetic properties. Five compounds have demonstrated potent activity against the P. falciparum in vitro (IC 50 values ranging from 1.7 to 15.2 μg mL -1 ), with moderate or low cytotoxicity against the HeLa cell line. The substitution of the carbonyl group in 6 by a 2,4-dinitrophenylhydrazone group (to afford 11) increases the Selective Index. These preliminary results indicate curcumin derivatives as potential antimalarial compounds. (author)

  7. Synthesis and Antitumor Evaluation of Novel Bis-Triaziquone Derivatives

    Directory of Open Access Journals (Sweden)

    Yuh-Ling Lin

    2009-06-01

    Full Text Available Aziridine-containing compounds have been of interest as anticancer agents since late 1970s. The design, synthesis and study of triaziquone (TZQ analogues with the aim of obtaining compounds with enhanced efficacy and reduced toxicity are an ongoing research effort in our group. A series of bis-type TZQ derivatives has been prepared and their cytotoxic activities were investigated. The cytotoxicity of these bis-type TZQ derivatives were tested on three cancer lines, including breast cancer (BC-M1, oral cancer (OEC-M1, larynx epidermal cancer (Hep2 and one normal skin fibroblast (SF. Most of these synthetic derivatives displayed significant cytotoxic activities against human carcinoma cell lines, but weak activities against SF. Among tested analogues the bis-type TZQ derivative 1a showed lethal effects on larynx epidermal carcinoma cells (Hep2, with an LC50 value of 2.02 mM, and also weak cytotoxic activity against SF cells with an LC50 value over 10 mM for 24 hr treatment. Comparing the viability of normal fibroblast cells treated with compound 1a and TZQ, the LC50 value of the latter was 2.52 mM, indicating more toxicity than compound 1a. This significantly decreased cytotoxicity of compound 1a towards normal SF cells, while still maintaining the anticancer activity towards Hep2 cells is an interesting feature. Among the seven compounds synthesized, compound 1c has similar toxicity effects on the three cancer cell lines and SF normal cells as the TZQ monomer.

  8. The retro Grignard addition reaction revisited: the reversible addition of benzyl reagents to ketones

    DEFF Research Database (Denmark)

    Christensen, Stig Holden; Holm, Torkil; Madsen, Robert

    2014-01-01

    transformation. The retro benzyl reaction was shown by the addition of benzylmagnesium chloride to di-tert-butyl ketone followed by exchange of both the benzyl and the ketone moiety with another substrate. Similar experiments were performed with phenylmagnesium bromide and tert-butylmagnesium chloride...

  9. A condition metric for Eucalyptus woodland derived from expert evaluations.

    Science.gov (United States)

    Sinclair, Steve J; Bruce, Matthew J; Griffioen, Peter; Dodd, Amanda; White, Matthew D

    2018-02-01

    The evaluation of ecosystem quality is important for land-management and land-use planning. Evaluation is unavoidably subjective, and robust metrics must be based on consensus and the structured use of observations. We devised a transparent and repeatable process for building and testing ecosystem metrics based on expert data. We gathered quantitative evaluation data on the quality of hypothetical grassy woodland sites from experts. We used these data to train a model (an ensemble of 30 bagged regression trees) capable of predicting the perceived quality of similar hypothetical woodlands based on a set of 13 site variables as inputs (e.g., cover of shrubs, richness of native forbs). These variables can be measured at any site and the model implemented in a spreadsheet as a metric of woodland quality. We also investigated the number of experts required to produce an opinion data set sufficient for the construction of a metric. The model produced evaluations similar to those provided by experts, as shown by assessing the model's quality scores of expert-evaluated test sites not used to train the model. We applied the metric to 13 woodland conservation reserves and asked managers of these sites to independently evaluate their quality. To assess metric performance, we compared the model's evaluation of site quality with the managers' evaluations through multidimensional scaling. The metric performed relatively well, plotting close to the center of the space defined by the evaluators. Given the method provides data-driven consensus and repeatability, which no single human evaluator can provide, we suggest it is a valuable tool for evaluating ecosystem quality in real-world contexts. We believe our approach is applicable to any ecosystem. © 2017 State of Victoria.

  10. Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

    International Nuclear Information System (INIS)

    Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho

    2013-01-01

    A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC 50 = 2.3 ± 0.7 μM) and AChE (IC 50 = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K i ) value to BuChE is 2.91 ± 0.15 μM

  11. Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of)

    2013-11-15

    A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC{sub 50} = 2.3 ± 0.7 μM) and AChE (IC{sub 50} = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K{sub i}) value to BuChE is 2.91 ± 0.15 μM.

  12. Entrepreneur environment management behavior evaluation method derived from environmental economy.

    Science.gov (United States)

    Zhang, Lili; Hou, Xilin; Xi, Fengru

    2013-12-01

    Evaluation system can encourage and guide entrepreneurs, and impel them to perform well in environment management. An evaluation method based on advantage structure is established. It is used to analyze entrepreneur environment management behavior in China. Entrepreneur environment management behavior evaluation index system is constructed based on empirical research. Evaluation method of entrepreneurs is put forward, from the point of objective programming-theory to alert entrepreneurs concerned to think much of it, which means to take minimized objective function as comprehensive evaluation result and identify disadvantage structure pattern. Application research shows that overall behavior of Chinese entrepreneurs environmental management are good, specially, environment strategic behavior are best, environmental management behavior are second, cultural behavior ranks last. Application results show the efficiency and feasibility of this method. Copyright © 2013 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  13. Synthesis, characterization and pharmacological evaluation of substituted phenoxy acetamide derivatives

    Directory of Open Access Journals (Sweden)

    Rani Priyanka

    2015-01-01

    Full Text Available A novel series of 2-(substituted phenoxy-N-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylacetamide and N-(2-bromocyclohexyl-2-(substituted phenoxyacetamide derivatives having cyclohexyl nucleus as common in both types were synthesized and assessed for their anti-inflammatory activity by a carrageenan induced rat paw oedema method, analgesic activity by Eddy’s hot plate method and antipyretic activity by brewer’s yeast induced pyrexia method. All the novel derivatives have been synthesized by the reaction of camphor and similar ketone having cyclohexane nucleus (e.g. 2-bromocyclohexanone with ammonium carbonate and formic acid resulting in the formation of aromatic amines (1a-b. These amines on further chloroacetylation with chloroacetylchloride give compounds (2a-b. Compounds (2a-b are converted to 2-(substituted phenoxy-N-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl acetamide and N-(2-bromocyclohexyl-2-(substituted phenoxyacetamide derivatives on treatment with substituted phenol. Among the series 3a-f, 3i, 3k, 3l compounds showed significant anti-inflammatory activity as compared to the standard drug diclofenac sodium and also compound 3a-f, 3h, 3j, 3k exhibit significant analgesic activity as compared to the standard drug. Compounds 3a-f and 3k showed antipyretic activity nearly to the standard drug indomethacin. Compounds 3a-f and 3k possess anti-inflammatory, analgesic and antipyretic activities near to the standard.

  14. Evaluation of catalytic combustion of actual coal-derived gas

    Science.gov (United States)

    Blanton, J. C.; Shisler, R. A.

    1982-01-01

    The combustion characteristics of a Pt-Pl catalytic reactor burning coal-derived, low-Btu gas were investigated. A large matrix of test conditions was explored involving variations in fuel/air inlet temperature and velocity, reactor pressure, and combustor exit temperature. Other data recorded included fuel gas composition, reactor temperatures, and exhaust emissions. Operating experience with the reactor was satisfactory. Combustion efficiencies were quite high (over 95 percent) over most of the operating range. Emissions of NOx were quite high (up to 500 ppm V and greater), owing to the high ammonia content of the fuel gas.

  15. {sup 1} H and {sup 13} C NMR studies on the enoling of 5-benzyl barbituric acids; Estudos por H-1 e C-13 RMN da enolizacao de acidos 5-benzil barbituricos

    Energy Technology Data Exchange (ETDEWEB)

    Villar, Jose Daniel Figueroa; Santos, Nedina Lucia dos; Cruz, Elizabete Rangel [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Secao de Quimica

    1992-12-31

    This work shows that the derivatives of the 5-benzyl barbituric acids hydroxylated at the ortho position of the aromatic ring only exist in the enol form. and that the alkylation of this hydroxyl gives products which exist mainly in the ketone form of the DMSO 5 refs., 2 figs., 2 tabs.

  16. Synthesis and pharmacological activity evaluation of arctigenin monoester derivatives.

    Science.gov (United States)

    Chen, Qiulian; Yang, Limin; Han, Mei; Cai, Enbo; Zhao, Yan

    2016-12-01

    Arctigenin (ARG), a nature medicine with many pharmacological activities, was poorly soluble in water and placed restriction on practical usage. Six novel arctigenin monoester derivatives were obtained from the reflux reaction with arctigenin, carboxylic acids (crotonic acid, furoic acid, 2-naphthalene acid and indol-3-acetic acid), EDCI and DMAP in dichloromethane at 60°C for 4-6h and their properties on nitrite scavenging assay were investigated in vitro. Based on the results, the one of the most effective derivatives, arctigenin β-indolylacetate (ARG6), was selected to study anti-tumor activity in vivo at doses of 20 and 40mg/kg. The results showed that comparison with ARG group, ARG6 exhibited more anti-tumor activity in H22 tumor-bearing mice. Furthermore, ARG6 exhibited less damage to the liver, kidney, spleen and thymus when compared with those in positive group. Biochemical parameters of ALT, AST, BUN and Cre showed ARG6 had little toxicity to mice as well. ARG6 significantly improved serum cytokine levels of IL-2, IL-6, IFN-γ and TNF-α, and decreased VEGF compared with ARG. Moreover, H & E staining, TUNEL assay and immunohistochemical of tumor issues also indicated that ARG6 exhibited anti-tumor activity in vivo. In brief, the present study provide a method to improve ARG anti-tumor activity and provide a reference for new anti-tumor agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Synthesis and Biological Evaluation of Some Novel Dithiocarbamate Derivatives

    Directory of Open Access Journals (Sweden)

    Begüm Nurpelin Sağlık

    2014-01-01

    Full Text Available 18 novel dithiocarbamate derivatives were synthesized in order to investigate their inhibitory potency on acetylcholinesterase enzyme and antimicrobial activity. Structures of the synthesized compounds were elucidated by spectral data and elemental analyses. The synthesized compounds showed low enzyme inhibitory activity. However, they displayed good antimicrobial activity profile. Antibacterial activity of compounds 4a, 4e, and 4p (MIC = 25 μg/mL was equal to that of chloramphenicol against Klebsiella pneumoniae (ATCC 700603 and Escherichia coli (ATCC 35218. Most of the compounds exhibited notable antifungal activity against Candida albicans (ATCC 10231, Candida glabrata (ATCC 90030, Candida krusei (ATCC 6258, and Candida parapsilosis (ATCC 7330. Moreover, compound 4a, which carries piperidin-1-yl substituent and dimethylthiocarbamoyl side chain as variable group, showed twofold better anticandidal effect against all Candida species than reference drug ketoconazole.

  18. Synthesis, radioiodination and biological evaluation of a novel phthalimide derivative

    International Nuclear Information System (INIS)

    Motaleb, M.A.; Abdel-Ghaney, I.Y.; Shamsel-Din, H.A.; Abdel-Bary, H.M.

    2016-01-01

    Biologically active novel phthalimide derivative, N-(5-(2-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phthalimide (HPZPHT), was synthesized in excellent yield and characterized by IR, mass and 1 H NMR spectroscopy. It was radiolabeled with iodine-131 by direct electrophilic substitution reaction and radiochemical yield was determined by using different chromatographic techniques (HPLRC, paper chromatography and paper electrophoresis). 131 I-HPZPHT has high radiolabeling yield (98.00 ± 2.00 %), stability, solid tumor uptake and T/NT ratio (5.17 ± 0.03 at 30 min. post-injection) compared with many new tracers which have been developed in recent years. This study encourages the possible use of this tracer as a potential imaging and/or therapeutic agent for cancer. (author)

  19. Synthesis and anti-depressant evaluation of novel pyrazolone derivatives

    Directory of Open Access Journals (Sweden)

    Vijay Kumar Merugumolu

    2016-06-01

    Full Text Available Diazotization of substituted anilines with NaNO2 and concentrated hydrochloric acid at 0ºC gave the diazonium chlorides. Coupling of substituted aryl diazonium chlorides with ethyl acetoacetate in methanol gave ethyl-2-aryl-hydrazono-3-oxobutyrates (2a-h. Reaction of (2a-h with naphthoic carbohydrazide (3 gave the title compounds pyrazolone derivatives (4a-h. The newly synthesized compounds were screened for their in vivo anti-depressant activity by tail suspension test and forced swimming test. Some of the tested compounds 4f, 4g showed very good activity when compared to the standard drug imipramine. The newly synthesized compounds were characterized by physical parameters and the structures were elucidated by spectral data.

  20. Evaluation of terrestrial photogrammetric point clouds derived from thermal imagery

    Science.gov (United States)

    Metcalf, Jeremy P.; Olsen, Richard C.

    2016-05-01

    Computer vision and photogrammetric techniques have been widely applied to digital imagery producing high density 3D point clouds. Using thermal imagery as input, the same techniques can be applied to infrared data to produce point clouds in 3D space, providing surface temperature information. The work presented here is an evaluation of the accuracy of 3D reconstruction of point clouds produced using thermal imagery. An urban scene was imaged over an area at the Naval Postgraduate School, Monterey, CA, viewing from above as with an airborne system. Terrestrial thermal and RGB imagery were collected from a rooftop overlooking the site using a FLIR SC8200 MWIR camera and a Canon T1i DSLR. In order to spatially align each dataset, ground control points were placed throughout the study area using Trimble R10 GNSS receivers operating in RTK mode. Each image dataset is processed to produce a dense point cloud for 3D evaluation.

  1. Evaluation of cyanobacteria cell count detection derived from ...

    Science.gov (United States)

    Inland waters across the United States (US) are at potential risk for increased outbreaks of toxic cyanobacteria (Cyano) harmful algal bloom (HAB) events resulting from elevated water temperatures and extreme hydrologic events attributable to climate change and increased nutrient loadings associated with intensive agricultural practices. Current monitoring efforts are limited in scope due to resource limitations, analytical complexity, and data integration efforts. The goals of this study were to validate a new ocean color algorithm for satellite imagery that could potentially be used to monitor CyanoHAB events in near real-time to provide a compressive monitoring capability for freshwater lakes (>100 ha). The algorithm incorporated narrow spectral bands specific to the European Space Agency’s (ESA’s) MEdium Resolution Imaging Spectrometer (MERIS) instrument that were optimally oriented at phytoplankton pigment absorption features including phycocyanin at 620 nm. A validation of derived Cyano cell counts was performed using available in situ data assembled from existing monitoring programs across eight states in the eastern US over a 39-month period (2009–2012). Results indicated that MERIS provided robust estimates for Low (10,000–109,000 cells/mL) and Very High (>1,000,000 cells/mL) cell enumeration ranges (approximately 90% and 83%, respectively). However, the results for two intermediate ranges (110,000–299,000 and 300,000–1,000,000 cells/mL)

  2. Rate and Product Studies of Solvolyses of Benzyl Fluoroformate

    Directory of Open Access Journals (Sweden)

    Dennis N. Kevill

    2006-07-01

    Full Text Available The specific rates of solvolysis of benzyl fluoroformate have been measured inseveral hydroxylic solvents at 25.0 °C. For methanolysis, the solvent deuterium isotopeeffect and activation parameters were determined and activation parameters were alsodetermined for solvolyses in ethanol and 80% ethanol. For several of the binary hydroxylicsolvents, measurement of product ratios allowed selectivity values to be determined. Anextended Grunwald–Winstein treatment of the data led to sensitivities to changes in solventnucleophilicity and ionizing power. Comparison with previously determined specific ratesfor solvolysis of the chloroformate gave fluorine/chlorine rate ratios greater than unity. Allof the determinations made were consistent with an addition–elimination (association–dissociation mechanism, with addition rate-determining.

  3. 1-Benzyl-5-bromoindoline-2,3-dione

    Directory of Open Access Journals (Sweden)

    Yassine Kharbach

    2016-04-01

    Full Text Available In the title compound, C15H10BrNO2, the indoline ring system, the two ketone O atoms and the Br atom lie in a common plane, with the largest deviation from the mean plane being 0.073 (1 Å for the Br atom. The fused-ring system is nearly perpendicular to the benzyl ring, as indicated by the dihedral angle between them of 74.58 (10°. In the crystal, molecules are linked by weak C—H...O hydrogen bonds and by π–π interactions [inter-centroid distance = 3.625 (2 Å], forming a two-dimensional structure.

  4. Structure and dynamics at the liquid surface of benzyl alcohol

    International Nuclear Information System (INIS)

    Dietter, J.; Morgner, H.

    1999-01-01

    A molecular dynamics simulation of a liquid layer of benzyl alcohol has been performed in order to compare the results with those obtained in experimental studies of our group. The main result of the experimental work was a strong orientational ordering of the benzyl alcohol molecules in the surface as well as an exceptionally large surface potential of ca. 0.6 V. According to the experiments the surface molecules orientate in such a way that the benzene ring points toward the vapor phase while the CH 2 group and the OH group are directed towards the bulk of the liquid. The simulation confirms this orientation of the surface molecules. The surface potential resulting from the simulation is 350 mV. The simulation reveals that the rather large surface potential can be understood as a consequence of the mean orientation of the molecular dipole moment in the surface region. The mean orientation of the molecules themselves in the surface is due to the tendency of the system to maintain the hydrogen bonding structure of the bulk in the surface region as well. The preferential orientation of the surface molecules causes a change of the dynamics of the individual components of the molecules when switching from bulk to surface which depends on the separation of these components from the polar group. This becomes most obvious in case of the reorientation dynamics of the molecular axes, e.g. the reorientation of the benzene ring is faster than the reorientation of the OH group. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. Toxicological Evaluation of Lactase Derived from Recombinant Pichia pastoris

    Science.gov (United States)

    Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao

    2014-01-01

    A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50) based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure) did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system. PMID:25184300

  6. Toxicological evaluation of lactase derived from recombinant Pichia pastoris.

    Directory of Open Access Journals (Sweden)

    Shiying Zou

    Full Text Available A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50 based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system.

  7. Design synthesis and biological evaluation of 2-methylphenyl semicarbazone derivatives

    Directory of Open Access Journals (Sweden)

    Manmohan Singhal

    2011-03-01

    Full Text Available We have used pharmacophore hybridization technique of drug design and designed a pharmacophore model 2-methylphenylsemicarbazone which is having hydrogen acceptor site, hydrogen donor site, lipophilic site etc using ligandscout-2.02 software. A series of 2-methylphenyl-semicarbazone was synthesized and evaluated for their antipyretic activity using boiled cow milk induced pyrexia in rabbits. Compound 11 was the most active compound. The possible metabolites of some selected synthesized chalconesemicarbazones were predicted by computational method using Pallas version-3.1 ADME-Tox prediction software. The major pathway of metabolism was found to be p-hydroxylation and amide hydrolysis.

  8. Synthesis and pharmacological evaluation of several N-(2-nitrophenylpiperazine derivatives

    Directory of Open Access Journals (Sweden)

    DEANA ANDRIC

    2007-05-01

    Full Text Available Six newly synthesized heterocyclic (2-nitrophenylpiperazines, with a specific structure of the heteroaryl group, whichmimics the catechol moiety of dopamine (benzimidazoles and substituted benzimidazoles, were evaluated for their binding affinity to rat dopamine (DA, serotonin (5-HT and α1 receptors. All compounds with a benzimidazole group had a 5-HT2A/D2 receptors binding ratio characteristic for atypical neuroleptics (>1, pKi values. Compound 7c, 4-bromo-6-{2-[4-(2-nitrophenylpiperazin-1-yl]ethyl}-1H-benzimidazole, expressed higher affinities for all receptor classes than clozapine. Also, it exhibited the best characteristic for atypical neuroleptics and presents a compound with the best profile for further in vivo investigations.

  9. 1D AND 2D NMR STUDIES OF BENZYL O–VANILLIN

    Directory of Open Access Journals (Sweden)

    Mohammed Hadi Al–Douh

    2010-06-01

    Full Text Available The reaction of o-vanillin A with benzyl bromide B2 in acetone as the solvent and K2CO3 as a base in the presence of tetra-n-butylammonium iodide (TBAI as catalyst formed benzyl o-vanillin, C. The complete assignments of C using PROTON, APT, DEPT-135, COSY, NOESY, HMQC and HMBC NMR in both CDCl3 and acetone-d6 are discussed, and the coupling constants J are reported in Hertz (Hz.     Keywords: 1H NMR; 13C NMR; 2D NMR; Benzyl o-Vanillin

  10. The Evaluation of Novel Camphor-derived Ligands as Catalysts in ...

    African Journals Online (AJOL)

    The evaluation of a series of camphor-derived ligands as catalysts in the asymmetric Henry reaction is reported. The synthesis of two novel derivatives is detailed and these molecules are also screened as catalysts in this reaction. The single crystal X-ray structure of one of the novel compounds is reported. The reaction is ...

  11. Derivation and evaluation of a labeled hedonic scale.

    Science.gov (United States)

    Lim, Juyun; Wood, Alison; Green, Barry G

    2009-11-01

    The objective of this study was to develop a semantically labeled hedonic scale (LHS) that would yield ratio-level data on the magnitude of liking/disliking of sensation equivalent to that produced by magnitude estimation (ME). The LHS was constructed by having 49 subjects who were trained in ME rate the semantic magnitudes of 10 common hedonic descriptors within a broad context of imagined hedonic experiences that included tastes and flavors. The resulting bipolar scale is statistically symmetrical around neutral and has a unique semantic structure. The LHS was evaluated quantitatively by comparing it with ME and the 9-point hedonic scale. The LHS yielded nearly identical ratings to those obtained using ME, which implies that its semantic labels are valid and that it produces ratio-level data equivalent to ME. Analyses of variance conducted on the hedonic ratings from the LHS and the 9-point scale gave similar results, but the LHS showed much greater resistance to ceiling effects and yielded normally distributed data, whereas the 9-point scale did not. These results indicate that the LHS has significant semantic, quantitative, and statistical advantages over the 9-point hedonic scale.

  12. Navier-Stokes Predictions of Dynamic Stability Derivatives: Evaluation of Steady-State Methods

    National Research Council Canada - National Science Library

    DeSpirito, James; Silton, Sidra I; Weinacht, Paul

    2008-01-01

    The prediction of the dynamic stability derivatives-roll-damping, Magnus, and pitch-damping moments-were evaluated for three spin-stabilized projectiles using steady-state computational fluid dynamic (CFD) calculations...

  13. Simultaneous determination of paracetamol, 4-Aminophenol, 4-Chloroacetanilid, Benzyl alcohol,Benzaldehyde and EDTA by HPLC methodin paracetamol injection ampoule

    Directory of Open Access Journals (Sweden)

    Ali Merrikhi Khosroshahi

    2016-06-01

    Full Text Available Paracetamol that is known as acetaminophen have the most consume as an analgesic and antipyretic drug in the world. That is formulated in single compound or mixture at many forms such as tablets, syrups, suspensions and drops. The last form is intravenous injections. Paracetamol derived from 4-minophenol which is synthesized by acylated the P-acetaminophenol and acetic anhydride. 4-aminophenol is the main impurity at manufacturing of paracetamol which could produce by hydrolysis during storage or synthesis under normal conditions (temperature, pH, etc.. Also, 4-chloroacetanilid may be observed as an impurity in the raw material of paracetamol synthesis. Benzyl alcohol is a preservative that used in Paracetamol for injection. It will be very important if there are analytical techniques to measuring paracetamol and its degradation products accurately and easily. Undoubtedly the most important and widely used, separation technique is chromatography. There are several reports about separation and quantitative determination of paracetamol lonely or simultaneous determination of paracetamol and 4-aminophenol. In this paper investigated simultaneous determination of paracetamol, 4-aminophenol, 4-chloroacetanilid, benzyl alcohol, benzaldehyde, and EDTA in paracetamol for injection ampoules by high performance liquid chromatography. By changing the ratio of mixing methanol and acetonitrile as mobile phase at the wavelength of 215 nm and pH=3 separation of all compounds were completely done.

  14. A convenient procedure for the synthesis of allyl and benzyl ethers ...

    Indian Academy of Sciences (India)

    Unknown

    Department of Chemistry, Pondicherry University, Pondicherry 605 014, .... organic synthesis we hope that the procedure described in this paper will find ... Allyl bromide (Fluka) and benzyl bromide (E Merck) were freshly distilled before use.

  15. Postprocedural pain in shoulder arthrography: differences between using preservative-free normal saline and normal saline with benzyl alcohol as an intraarticular contrast diluent.

    Science.gov (United States)

    Storey, Troy F; Gilbride, George; Clifford, Kelly

    2014-11-01

    The purpose of this study was to prospectively evaluate the effect of benzyl alcohol, a common preservative in normal saline, on postprocedural pain after intraarticular injection for direct shoulder MR arthrography. From April 2011 through January 2013, 138 patients underwent direct shoulder MR arthrography. Using the Wong-Baker Faces Pain Scale, patients were asked to report their shoulder pain level immediately before and immediately after the procedure and then were contacted by telephone 6, 24, and 48 hours after the procedure. Fourteen patients did not receive the prescribed amount of contrast agent for diagnostic reasons or did not complete follow-up. Sixty-two patients received an intraarticular solution including preservative-free normal saline (control group) and 62 patients received an intraarticular solution including normal saline with 0.9% benzyl alcohol as a contrast diluent (test group). Patients were randomized as to which intraarticular diluent they received. Fluoroscopic and MR images were reviewed for extracapsular contrast agent administration or extravasation, full-thickness rotator cuff tears, and adhesive capsulitis. The effect of preservative versus control on pain level was estimated with multiple regression, which included time after procedure as the covariate and accounted for repeated measures over patients. Pain scale scores were significantly (p = 0.0382) higher (0.79 units; 95% CI, 0.034-1.154) with benzyl alcohol preservative compared with control (saline). In both study arms, the pain scale scores decreased slightly after the procedure, increased by roughly 1 unit over baseline for the test group and 0.3 unit over baseline for the control group by 6 hours after the procedure, were 0.50 unit over baseline for the test group and 0.12 unit over baseline for the control group at 24 hours, then fell to be slightly greater than baseline at 48 hours with benzyl alcohol and slightly less than baseline without benzyl alcohol. These trends

  16. Kinetic Studies on the Selective Oxidation of Benzyl Alcohols in Organic Medium under Phase Transfer Catalysis

    Directory of Open Access Journals (Sweden)

    K. Bijudas

    2014-07-01

    Full Text Available Kinetic studies on the oxidation of benzyl alcohol and substituted benzyl alcohols in benzene as the reaction medium have been studied by using potassium dichromate under phase transfer catalysis (PTC. The phase transfer catalysts (PT catalysts used were tetrabutylammonium bromide (TBAB and tetrabutylphosphonium bromide (TBPB.  Benzyl alcohols were selectively oxidised to corresponding benzaldehydes in good yield (above 90%.  The order of reactivity among the studied benzyl alcohols is p - OCH3 > p - CH3 > - H > p - Cl.  Plots of log k2 versus Hammett's substituent constant (s has been found to be curve shaped and this suggests that there should be a continuous change in transition state with changes in substituent present in the substrate from electron donating to electron withdrawing. A suitable mechanism has been suggested in which the rate determining step involves both C - H bond cleavage and C - O bond formations in concerted manner. © 2014 BCREC UNDIP. All rights reserved.Received: 16th March 2014; Revised: 18th May 2014; Accepted: 18th May 2014[How to Cite: Bijudas, K., Bashpa, P., Nair, T.D.R. (2014. Kinetic Studies on the Selective Oxidation of Benzyl Alcohol and Substituted Benzyl Alcohols in Organic Medium under Phase Transfer Catalysis. Bulletin of Chemical Reaction Engineering & Catalysis, 9 (2: 142-147. (doi:10.9767/bcrec.9.2.6476.142-147][Permalink/DOI: http://dx.doi.org/10.9767/bcrec.9.2.6476.142-147] 

  17. 5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a series of anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar structure-activity relationship profile.

    Science.gov (United States)

    Nawrozkij, Maxim B; Rotili, Dante; Tarantino, Domenico; Botta, Giorgia; Eremiychuk, Alexandre S; Musmuca, Ira; Ragno, Rino; Samuele, Alberta; Zanoli, Samantha; Armand-Ugón, Mercedes; Clotet-Codina, Imma; Novakov, Ivan A; Orlinson, Boris S; Maga, Giovanni; Esté, José A; Artico, Marino; Mai, Antonello

    2008-08-14

    A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2-oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro-, 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl- S-DABOs, 6-8) is here described. The new compounds showed low micromolar to low nanomolar (in one case subnanomolar) inhibitory activity against wt HIV-1. Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in enzyme (wt and K103N, Y181I, and L100I mutated RTs) assays, compounds carrying an ethyl/ iso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety at C6 were the most potent derivatives, also characterized by low fold resistance ratio. Interestingly, the structure-activity relationship (SAR) data drawn from this DABO series are more related to HEPT than to DABO derivatives. These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs.

  18. Intercomparison of derived integral data from evaluated data libraries of the actinides

    International Nuclear Information System (INIS)

    Paviotti Corcuera, R.

    1988-12-01

    Resonance integrals and fission spectrum averaged cross-sections are calculated for the actinides from all recent major evaluated libraries. Whenever possible the results are compared against measurements. It is found that the experimental data are scarce and that there exist considerable differences between experimentally measured data and those derived from the evaluated libraries. (author). 93 refs and tabs

  19. Toxicity of benzyl alcohol in adult and neonatal mice

    International Nuclear Information System (INIS)

    McCloskey, S.E.

    1987-01-01

    Benzyl alcohol (BA) is an aromatic alcohol, which is used as a bacteriostat in a variety of parenteral preparations. In 1982, it was implicated as the agent responsible for precipitating The Gasping Syndrome in premature neonates. The investigate further this toxicity, BA was administered, intraperiotoneally, to adult and neonatal CD-1 male mice. Gross behavioral changes were monitored. Low doses produced minimal toxic effects within an initial 4 hour observation period. At the end of this time, the LD 50 was determined to be 1000 mg/kg for both age groups. Death was due to respiratory arrest in all cases. Rapid absorption and conversion of BA to its primary metabolite, benzaldehyde, was demonstrated by gas chromatographic analysis of plasma from both experimental groups. The conversion of BA to benzaldehyde was confirmed in in vitro by using both horse-liver and mouse liver ADH. The inhibition of alcohol dehydrogenase (ADH) by pyrazole was similarly demonstrated in both enzyme systems. 14 C-labelled BA was utilized to determine the distribution of BA and its metabolites in the body, and to possibly pinpoint a target organ of toxicity

  20. 3 Benzyl-6-chloropyrone: a suicide inhibitor of cholesterol esterase

    International Nuclear Information System (INIS)

    Saint, C.; Gallo, I.; Kantorow, M.; Bailey, J.M.

    1986-01-01

    Cholesterol, absorbed from the intestine, appears in lymph as the ester. Cholesterol esterase is essential for this process, since depletion of the enzyme blocks and repletion restores, absorption. Selective inhibitors of cholesterol esterase may thus prove useful in reducing cholesterol uptake. A series of potential suicide substrates were synthesized which, following cleavage by the enzyme, would attack the putative nucleophile in the active site. One of these, 3-benzyl-6-chloropyrone (3BCP), inhibited both synthesis and hydrolysis of 14 C-cholesteryl oleate with an I 50 of approximately 150 μM. The inactivation was time-dependent and characteristic of a suicide mechanism. The α pyrone structure (lactone analog) is cleaved by a serine-hydroxyl in the active site. This generates an enoyl chloride which inactivates the imidazole believed to play a part in the catalytic function of the enzyme. Inhibition by 3BCP is selective for cholesterol esterase. The activity of pancreatic lipase as not affected by concentrations up to 1 mM

  1. Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.

    Science.gov (United States)

    Shen, Sida; Zhuang, Jingjing; Chen, Yijia; Lei, Min; Chen, Jing; Shen, Xu; Hu, Lihong

    2013-07-01

    A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Category 2 and 4 investigation-derived waste readiness evaluation plan

    International Nuclear Information System (INIS)

    Ludowise, J.D.

    1996-08-01

    This Readiness Evaluation Plan presents the methodology used to assess the readiness for loading investigation-derived waste drums on trucks for transport to the Environmental Restoration Disposal Facility. The scope of this plan includes an assessment of the organizations, procedures, and regulatory approvals necessary for the handling of investigation-derived waste containers and the subsequent transportation of materials to the Environmental Restoration Disposal Facility

  3. Evaluating the Wald entropy from two-derivative terms in quadratic actions

    International Nuclear Information System (INIS)

    Brustein, Ram; Gorbonos, Dan; Hadad, Merav; Medved, A. J. M.

    2011-01-01

    We evaluate the Wald Noether charge entropy for a black hole in generalized theories of gravity. Expanding the Lagrangian to second order in gravitational perturbations, we show that contributions to the entropy density originate only from the coefficients of two-derivative terms. The same considerations are extended to include matter fields and to show that arbitrary powers of matter fields and their symmetrized covariant derivatives cannot contribute to the entropy density. We also explain how to use the linearized gravitational field equation rather than quadratic actions to obtain the same results. Several explicit examples are presented that allow us to clarify subtle points in the derivation and application of our method.

  4. EVALUATION OF ANTIOXIDANT ACTIVITY OF SOME IMINES DERIVATIVES OF L-ARGININE.

    Science.gov (United States)

    Iacob, Andreea-Teodora; Drăgan, Maria; Constantin, Sandra; Lupaşcu, Florentina; Confederat, Luminiţa; Buron, F; Routier, S; Profire, Lenuţa

    2016-01-01

    L-Arginine is an a-amino acid which plays important roles in different diseases or processes, such as Alzheimer disease, inflammatory process, healing and tissue regeneration and it also could be useful as an anti-atherosclerotic agent. Considering the large amount of studies on the beneficial effects of different antioxidants, this paper is focused on the evaluation of the antioxidant potential of some imine derivatives, synthesized by the authors and described in a previous article. The evaluation of the antioxidant power was performed using phosphomolydenum-reducing antioxidant power (PRAP) and ferric reducing antioxidant power (FRAP) assays, tests described in the literature and which are used with some minor modifications. It was found that most of the imine derivatives are more active than the L-Arginine in the PPAP and FRAP assays. The most active derivative was the compound obtained by condensation of L-arginine with 2,3-dihydroxybenzaldehyde (2k) and 2-nitrobenzaldehyde (2g). Following the described protocol, some imine derivatives of L-arginine were evaluated in terms of antioxidant potential using in vitro methods. The most favorable influence was obtained by the aromatic substitution with nitro and hydroxyl, the corresponding derivatives being the most active derivatives compared to L-arginine.

  5. Synthesis of Cycloveratrylene Macrocycles and Benzyl Oligomers Catalysed by Bentonite under Microwave/Infrared and Solvent-Free Conditions

    Directory of Open Access Journals (Sweden)

    Manuel Salmón

    2013-10-01

    Full Text Available Tonsil Actisil FF, which is a commercial bentonitic clay, promotes the formation of cycloveratrylene macrocycles and benzyl oligomers from the corresponding benzyl alcohols in good yields under microwave heating and infrared irradiation in the absence of solvent in both cases. The catalytic reaction is sensitive to the type of substituent on the aromatic ring. Thus, when benzyl alcohol was substituted with a methylenedioxy, two methoxy or three methoxy groups, a cyclooligomerisation process was induced. Unsubstituted, methyl and methoxy benzyl alcohols yielded linear oligomers. In addition, computational chemistry calculations were performed to establish a validated mechanistic pathway to explain the growth of the obtained linear oligomers.

  6. Friedel-Crafts reaction of benzyl fluorides: selective activation of C-F bonds as enabled by hydrogen bonding.

    Science.gov (United States)

    Champagne, Pier Alexandre; Benhassine, Yasmine; Desroches, Justine; Paquin, Jean-François

    2014-12-08

    A Friedel-Crafts benzylation of arenes with benzyl fluorides has been developed. The reaction produces 1,1-diaryl alkanes in good yield under mild conditions without the need for a transition metal or a strong Lewis acid. A mechanism involving activation of the C-F bond through hydrogen bonding is proposed. This mode of activation enables the selective reaction of benzylic C-F bonds in the presence of other benzylic leaving groups. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Dosimetric quantities and basic data for the evaluation of generalised derived limits

    International Nuclear Information System (INIS)

    Harrison, N.T.; Simmonds, J.R.

    1980-12-01

    The procedures, dosimetric quantities and basic data to be used for the evaluation of Generalised Derived Limits (GDLs) in environmental materials and of Generalised Derived Limits for discharges to atmosphere are described. The dosimetric considerations and the appropriate intake rates for both children and adults are discussed. In most situations in the nuclear industry and in those institutions, hospitals and laboratories which use relatively small quantities of radioactive material, the Generalised Derived Limits provide convenient reference levels against which the results of environmental monitoring can be compared, and atmospheric discharges can be assessed. They are intended for application when the environmental contamination or discharge to atmosphere is less than about 5% of the Generalised Derived Limit; above this level, it will usually be necessary to undertake a more detailed site-specific assessment. (author)

  8. Functional evaluation of bone marrow derived DC of tumor bearing mice after immunotherapy

    International Nuclear Information System (INIS)

    Li Min; Chen Cheng; Gu Tao; Zhou Huan; Zhang Feng; Zhu Yibei; Yu Gehua; Zhang Xueguang; Gu Zongjiang

    2006-01-01

    Objective: To evaluate the function of bone marrow derived DC of tumor bearing mice after immunotherapy. Methods: Tumor bearing mice were immunized with DC vaccine plus injection of agonistic anti-4-1BB monoclonal antibody. The proliferation of T cells primed with bone marrow derived DC of tumor bearing mice after immunotherapy was tested by 3 H-TdR incorporation. ELISA was employed to determine the levels of IL-2, IFN-γ and IL-10 secreted by DC primed T cells. Results: Bone marrow derived DC of tumor bearing mice was less efficient in stimulating the proliferation of T cells and IL-2 and IFN-γ secretion made by T cells. After immunotherapy, the proliferation of cells and IL-2 and IFN-γ secretionmade by T cells were enhanced. Conclusion: The function of bone marrow derived DC of tumor bearing mice after immunotherapy was ameliorated. (authors)

  9. The MMP inhibitor (R)-2-(N-benzyl-4-(2-[18F]fluoroethoxy)phenylsulphonamido) -N-hydroxy-3-methylbutanamide: Improved precursor synthesis and fully automated radiosynthesis

    International Nuclear Information System (INIS)

    Wagner, Stefan; Faust, Andreas; Breyholz, Hans-Joerg; Schober, Otmar; Schaefers, Michael; Kopka, Klaus

    2011-01-01

    Summary: The CGS 25966 derivative (R)-2-(N-Benzyl-4-(2-[ 18 F]fluoroethoxy)phenyl-sulphonamido) -N-hydroxy-3-methylbutanamide [ 18 F]9 represents a very potent radiolabelled matrix metalloproteinase inhibitor. For first human PET studies it is mandatory to have a fully automated radiosynthesis and a straightforward precursor synthesis available. The realisation of both requirements is reported herein. In particular, the corresponding precursor 8 was obtained in a reliable 7 step synthesis with an overall chemical yield of 2.3%. Furthermore, the target compound [ 18 F]9 was prepared with a radiochemical yield of 14.8±3.9% (not corrected for decay).

  10. Radiolysis of benzyl alcohol in aqueous solution by external gamma-irradiation

    International Nuclear Information System (INIS)

    Ikebuchi, Hideharu; Kido, Yasumasa; Urakubo, Goro

    1977-01-01

    Radiolysis of 0.05% aqueous solution of benzyl alcohol with 60 Co γ-rays ranging from 1 x 10 4 to 7 x 10 5 rad was investigated, in order to presume the change of it contained in radiopharmaceuticals. For both O 2 free and oxygenated solutions, an approximately linear relationship holds between the retaining benzyl alcohol and dose in the range from 1 x 10 5 to 7 x 10 5 rads. The G(-M) values of benzyl alcohol calculated from the relation were 2.34 in the absence and 1.92 in presence of oxygen. In the presence of oxygen, a main product was benzaldehyde and its G value was 0.87. In the absence of oxygen, the main products of the radiolysis were dibenzyl, benzyl phenylcalbinol and hydrobenzoin, which were regarded as the radical-reaction products of PhCH 2 and PhCHOH, and the yield of benzaldehyde was negligible. Irrespective of the presence of oxygen, o- and p-hydroxylated products of benzyl alcohol were found only in small quantity. (auth.)

  11. Solubilities of benzoic acid in binary (benzyl alcohol + benzaldehyde) solvent mixtures

    International Nuclear Information System (INIS)

    Wang, Hui; Wang, Qinbo; Xiong, Zhenhua; Chen, Chuxiong; Shen, Binwei

    2015-01-01

    Highlights: • Solubilities of benzoic acid in (benzyl alcohol + benzaldehyde) mixtures were measured at 1 atm. • The experimental temperature ranges at (298.35 to 355.65) K. • Effects of benzyl alcohol mass concentration at (0.00 to 1.00) on the solubilities of benzoic acid were studied. • The experimental data were correlated with NRTL model. • Thermodynamic functions of dissolution of benzoic acid in (benzyl alcohol + benzaldehyde) mixtures were discussed. - Abstract: The solubility of benzoic acid in binary (benzyl alcohol + benzaldehyde) solvent mixtures was measured at temperature from (298.35 to 355.65) K and atmospheric pressure. The measured solubility increases with the increasing temperature at constant solvent composition. The effects of mass fraction benzaldehyde in the solvent mixtures at (0.0 to 1.00) on the solubility were studied. The measured solubility decreases with the increasing mass fraction of benzaldehyde. The experimental results were correlated with the non-random two-liquid (NRTL) equations, and good agreement between the correlated and the experimental values was obtained. Thermodynamic functions for the solution of benzoic acid in binary (benzyl alcohol + benzaldehyde) solvent mixtures were calculated with the van’t Hoff plot. The apparent dissolution Gibbs free energy change was also calculated

  12. Student Response to Faculty Instruction (SRFI): An Empirically Derived Instrument to Measure Student Evaluations of Teaching

    Science.gov (United States)

    Beitzel, Brian D.

    2013-01-01

    The Student Response to Faculty Instruction (SRFI) is an instrument designed to measure the student perspective on courses in higher education. The SRFI was derived from decades of empirical studies of student evaluations of teaching. This article describes the development of the SRFI and its psychometric attributes demonstrated in two pilot study…

  13. Benzoic acid derivatives: Evaluation of thermochemical properties with complementary experimental and computational methods

    International Nuclear Information System (INIS)

    Verevkin, Sergey P.; Zaitsau, Dzmitry H.; Emeĺyanenko, Vladimir N.; Stepurko, Elena N.; Zherikova, Kseniya V.

    2015-01-01

    Highlights: • Vapor pressures of benzoic acid derivatives were measured. • Sublimation enthalpies were derived and compared with the literature. • Thermochemical data tested for consistency using additivity rules and computations. • Contradiction between available enthalpies of sublimation was resolved. • Pairwise interactions of substituents on the benzene ring were derived. - Abstract: Molar sublimation enthalpies of the methyl- and methoxybenzoic acids were derived from the transpiration method, static method, and TGA. Thermochemical data available in the literature were collected, evaluated, and combined with own experimental results. This collection together with the new experimental results reported here has helped to resolve contradictions in the available enthalpy data and to recommend sets of sublimation and formation enthalpies for the benzoic acid derivatives. Gas-phase enthalpies of formation calculated with the G4 quantum-chemical method were in agreement with the experiment. Pairwise interactions of the methyl, methoxy, and carboxyl substituents on the benzene ring were derived and used for the development of simple group-additivity procedures for estimation of the vaporization enthalpies, gas-phase, and liquid-phase enthalpies of formation of substituted benzenes.

  14. Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy.

    Science.gov (United States)

    Kudou, Naoki; Taniguchi, Akira; Sugimoto, Kenji; Matsuya, Yuji; Kawasaki, Masashi; Toyooka, Naoki; Miyoshi, Chika; Awale, Suresh; Dibwe, Dya Fita; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2013-02-01

    A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC(50), 0.49 μM), diethoxy derivative 4h (PC(50), 0.66 μM), and triethoxy derivative 4m (PC(50), 0.78 μM) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC(50), 0.80 μM). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  15. Benzoic acid derivatives: Evaluation of thermochemical properties with complementary experimental and computational methods

    Energy Technology Data Exchange (ETDEWEB)

    Verevkin, Sergey P., E-mail: sergey.verevkin@uni-rostock.de [Department of Physical Chemistry and Department “Science and Technology of Life, Light and Matter”, University of Rostock, D-18059 Rostock (Germany); Department of Physical Chemistry, Kazan Federal University, 420008 Kazan (Russian Federation); Zaitsau, Dzmitry H. [Department of Physical Chemistry, Kazan Federal University, 420008 Kazan (Russian Federation); Emeĺyanenko, Vladimir N. [Department of Physical Chemistry and Department “Science and Technology of Life, Light and Matter”, University of Rostock, D-18059 Rostock (Germany); Stepurko, Elena N. [Chemistry Faculty and Research Institute for Physical Chemical Problems, Belarusian State University, 220030 Minsk (Belarus); Zherikova, Kseniya V. [Nikolaev Institute of Inorganic Chemistry of Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk (Russian Federation)

    2015-12-20

    Highlights: • Vapor pressures of benzoic acid derivatives were measured. • Sublimation enthalpies were derived and compared with the literature. • Thermochemical data tested for consistency using additivity rules and computations. • Contradiction between available enthalpies of sublimation was resolved. • Pairwise interactions of substituents on the benzene ring were derived. - Abstract: Molar sublimation enthalpies of the methyl- and methoxybenzoic acids were derived from the transpiration method, static method, and TGA. Thermochemical data available in the literature were collected, evaluated, and combined with own experimental results. This collection together with the new experimental results reported here has helped to resolve contradictions in the available enthalpy data and to recommend sets of sublimation and formation enthalpies for the benzoic acid derivatives. Gas-phase enthalpies of formation calculated with the G4 quantum-chemical method were in agreement with the experiment. Pairwise interactions of the methyl, methoxy, and carboxyl substituents on the benzene ring were derived and used for the development of simple group-additivity procedures for estimation of the vaporization enthalpies, gas-phase, and liquid-phase enthalpies of formation of substituted benzenes.

  16. Poly-benzyl domains grown on porous silicon and their I-V rectification

    International Nuclear Information System (INIS)

    Chao Jie; Han Huanmei; Xia Bing; Ba Long; Liu Hongbo; Xiao Shoujun

    2007-01-01

    Microwave-irradiated polymerization of benzyl chloride and triphenyl chloromethane on hydride-terminated porous silicon (PS) was achieved through the use of Zn powder as a catalyst. Transmission infrared Fourier-transform spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses confirmed the poly-benzyl membranes grafted on PS. Topographical images by AFM revealed crystal-like domains rather than homogenous monolayers on the surface. The current-voltage measurements in nano-scale by current sensing atomic force microscopy (CS-AFM) showed the rectification behavior of this polymer membrane. Finally, mechanism of a radical initiation on the surface and a following Friedel-Crafts alkylation was proposed for the covalent assembly of poly-benzyl domains

  17. t-3-Benzyl-r-2,c-6-diphenylpiperidin-4-one oxime

    Directory of Open Access Journals (Sweden)

    R. Arulraj

    2016-12-01

    Full Text Available In the title compound, C24H24N2O [systematic name: (E-3-benzyl-2,6-diphenylpiperidin-4-one oxime], the piperidine ring adopts a slightly distorted chair conformation and the phenyl rings and the benzyl group substituents are attached equatorially. The oxime group makes a dihedral angle of 42.88 (12° with the piperidine ring. The dihedral angle between the phenyl rings is 71.96 (8°. The benzyl ring makes dihedral angles of 63.01 (8 and 59.35 (8° with the two phenyl rings. In the crystal, molecules are linked by O—H...N hydrogen bonds, forming C(7 chains along the c axis. The chains are linked by C—H...π interactions, forming slabs lying parallel to the bc plane.

  18. Evaluation gamma radiation in composite sisal fiber- polyurethane derived of castor oil by bending test

    International Nuclear Information System (INIS)

    Souza, Felipe H. de; Geraldo, Ricardo R.; Vasco, Marina C.; Azevedo, Elaine; Claro Neto, Salvador

    2015-01-01

    Materials used for making furniture and accessories or positioning in X -ray examination rooms should not exhale volatile organic compounds and are resistant to ionizing radiation. One solution is the use of vegetable fiber and polyurethane composites of vegetable origin, since they are biodegradable, derived from renewable raw materials and have no volatile organic compounds. The main difficulty in developing this material is fiber adhesion with the polymer. The objective of this study is to evaluate the mechanical properties of composite sisal fiber composite, without further treatment, and polyurethane derived from castor oil, with a dose of 25 kGy gamma radiation, subjected to 3 points bending tests. (author)

  19. Synthesis, crystal structure determination, biological screening and docking studies of N1-substituted derivatives of 2,3-dihydroquinazolin-4(1H)-one as inhibitors of cholinesterases.

    Science.gov (United States)

    Sultana, Nargis; Sarfraz, Muhammad; Tanoli, Saba Tahir; Akram, Muhammad Safwan; Sadiq, Abdul; Rashid, Umer; Tariq, Muhammad Ilyas

    2017-06-01

    Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry out the N 1 -substitution of 2,3-dihydroquinazolin-4(1H)-one core. A set of 32 N-alkylated/benzylated quinazoline derivatives were synthesized, characterized and evaluated for their inhibition against cholinesterases. N-alkylation of the series of the compounds reported previously (N-unsubstituted) resulted in improved activity. All the compounds showed inhibition of both enzymes in the micromolar to submicromolar range. Structure activity relationship (SAR) of the 32 derivatives showed that N-benzylated compounds possess good activity than N-alkylated compounds. N-benzylated compounds 2ad and 2af were found very active with their IC 50 values toward AChE in submicromolar range (0.8µM and 0.6µM respectively). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational predictions of ADMET studies reveal that all the compounds have good pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover, all the compounds are predicted to be absorbed in human intestine and also have the ability to cross blood brain barrier. Overall, the synthesized compounds have established a structural foundation for the design of new inhibitors of cholinesterase. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Experimental Determination and Modeling of the Phase Behavior for the Selective Oxidation of Benzyl Alcohol in Supercritical CO2

    DEFF Research Database (Denmark)

    Tsivintzelis, Ioannis; Beier, Matthias Josef; Grunwaldt, Jan-Dierk

    2011-01-01

    In this study the phase behavior of mixtures relevant to the selective catalytic oxidation of benzyl alcohol to benzaldehyde by molecular oxygen in supercritical CO2 is investigated. Initially, the solubility of N2 in benzaldehyde as well as the dew points of CO2–benzyl alcohol–O2 and CO2...

  1. Selective Tandem Synthesis of Oximes from Benzylic Alcohols Catalyzed with 2, 3-Dichloro-5, 6-dicyanobenzoquinone

    Energy Technology Data Exchange (ETDEWEB)

    Aghapour, Ghasem; Mohamadian, Samaneh [Damghan University, Damghan (Iran, Islamic Republic of)

    2012-04-15

    In spite of many reports in the literature concerning with oxidation of benzylic alcohols to carbonyl compounds with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in stoichiometric amounts or even more, we surprisingly found that benzylic alcohols are directly oxidized to oximes using a catalytic amount of DDQ in the presence of hydroxylamine hydrochloride under solvent-free conditions. The present tandem catalytic method can be efficiently used for preparation of oximes in the presence of some other functional groups with excellent chemoselectivity

  2. Kinetics and Mechanism of Oxidation of Benzyl Alcohol by Benzimidazolium Fluorochromate

    Directory of Open Access Journals (Sweden)

    J. Dharmaraja

    2008-01-01

    Full Text Available The kinetics of oxidation of benzyl alcohol (BzOH by benzimidazolium fluorochromate (BIFC has been studied in 50% aqueous acetic acid medium at 308 K. The reaction is first order with respect to [oxidant] and [benzyl alcohol]. The reaction is catalysed by hydrogen ions. The decrease in dielectric constant of the medium increases the rate of the reaction. Addition of sodium perchlorate increases the rate of the reaction appreciably. No polymerization with acrylonitrile. The reaction has been conducted at four different temperature and the activation parameters were calculated. From the observed kinetic results a suitable mechanism was proposed.

  3. Derivation of Two Critical Appraisal Scores for Trainees to Evaluate Online Educational Resources: A METRIQ Study

    Science.gov (United States)

    Chan, Teresa M.; Thoma, Brent; Krishnan, Keeth; Lin, Michelle; Carpenter, Christopher R.; Astin, Matt; Kulasegaram, Kulamakan

    2016-01-01

    Introduction Online education resources (OERs), like blogs and podcasts, increasingly augment or replace traditional medical education resources such as textbooks and lectures. Trainees’ ability to evaluate these resources is poor, and few quality assessment aids have been developed to assist them. This study aimed to derive a quality evaluation instrument for this purpose. Methods We used a three-phase methodology. In Phase 1, a previously derived list of 151 OER quality indicators was reduced to 13 items using data from published consensus-building studies (of medical educators, expert podcasters, and expert bloggers) and subsequent evaluation by our team. In Phase 2, these 13 items were converted to seven-point Likert scales used by trainee raters (n=40) to evaluate 39 OERs. The reliability and usability of these 13 rating items was determined using responses from trainee raters, and top items were used to create two OER quality evaluation instruments. In Phase 3, these instruments were compared to an external certification process (the ALiEM AIR certification) and the gestalt evaluation of the same 39 blog posts by 20 faculty educators. Results Two quality-evaluation instruments were derived with fair inter-rater reliability: the METRIQ-8 Score (Inter class correlation coefficient [ICC]=0.30, p<0.001) and the METRIQ-5 Score (ICC=0.22, p<0.001). Both scores, when calculated using the derivation data, correlated with educator gestalt (Pearson’s r=0.35, p=0.03 and r=0.41, p<0.01, respectively) and were related to increased odds of receiving an ALiEM AIR certification (odds ratio=1.28, p=0.03; OR=1.5, p=0.004, respectively). Conclusion Two novel scoring instruments with adequate psychometric properties were derived to assist trainees in evaluating OER quality and correlated favourably with gestalt ratings of online educational resources by faculty educators. Further testing is needed to ensure these instruments are accurate when applied by trainees. PMID

  4. Derivation of Two Critical Appraisal Scores for Trainees to Evaluate Online Educational Resources: A METRIQ Study

    Directory of Open Access Journals (Sweden)

    Teresa M. Chan

    2016-09-01

    Full Text Available Introduction: Online education resources (OERs, like blogs and podcasts, increasingly augment or replace traditional medical education resources such as textbooks and lectures. Trainees’ ability to evaluate these resources is poor, and few quality assessment aids have been developed to assist them. This study aimed to derive a quality evaluation instrument for this purpose. Methods: We used a three-phase methodology. In Phase 1, a previously derived list of 151 OER quality indicators was reduced to 13 items using data from published consensus-building studies (of medical educators, expert podcasters, and expert bloggers and subsequent evaluation by our team. In Phase 2, these 13 items were converted to seven-point Likert scales used by trainee raters (n=40 to evaluate 39 OERs. The reliability and usability of these 13 rating items was determined using responses from trainee raters, and top items were used to create two OER quality evaluation instruments. In Phase 3, these instruments were compared to an external certification process (the ALiEM AIR certification and the gestalt evaluation of the same 39 blog posts by 20 faculty educators. Results: Two quality-evaluation instruments were derived with fair inter-rater reliability: the METRIQ-8 Score (Inter class correlation coefficient [ICC]=0.30, p<0.001 and the METRIQ-5 Score (ICC=0.22, p<0.001. Both scores, when calculated using the derivation data, correlated with educator gestalt (Pearson’s r=0.35, p=0.03 and r=0.41, p<0.01, respectively and were related to increased odds of receiving an ALiEM AIR certification (odds ratio=1.28, p=0.03; OR=1.5, p=0.004, respectively. Conclusion: Two novel scoring instruments with adequate psychometric properties were derived to assist trainees in evaluating OER quality and correlated favourably with gestalt ratings of online educational resources by faculty educators. Further testing is needed to ensure these instruments are accurate when applied by

  5. Cardiotoxicity evaluation using human embryonic stem cells and induced pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Zhao, Qi; Wang, Xijie; Wang, Shuyan; Song, Zheng; Wang, Jiaxian; Ma, Jing

    2017-03-09

    Cardiotoxicity remains an important concern in drug discovery. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have become an attractive platform to evaluate cardiotoxicity. However, the consistency between human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in prediction of cardiotoxicity has yet to be elucidated. Here we screened the toxicities of four representative drugs (E-4031, isoprenaline, quinidine, and haloperidol) using both hESC-CMs and hiPSC-CMs, combined with an impedance-based bioanalytical method. It showed that both hESC-CMs and hiPSC-CMs can recapitulate cardiotoxicity and identify the effects of well-characterized compounds. The combined platform of hPSC-CMs and an impedance-based bioanalytical method could improve preclinical cardiotoxicity screening, holding great potential for increasing drug development accuracy.

  6. Synergistic effect in the oxidation of benzyl alcohol using citrate-stabilized gold bimetallic nanoparticles supported on alumina

    Energy Technology Data Exchange (ETDEWEB)

    Gómez-Villarraga, Fernando, E-mail: ferchogomezv@gmail.com; Radnik, Jörg; Martin, Andreas; Köckritz, Angela [Leibniz-Institut für Katalyse e.V. an der Universität Rostock (Germany)

    2016-06-15

    Bimetallic nanoparticles (NPs) containing gold and various second metals (M = Pd, Pt, Cu, and Ag) supported on alumina (AuM/Alumina) were prepared using sodium citrate as stabilizer. In addition, supported monometallic Au/Alumina and Pd/Alumina were synthesized and tested to reveal synergistic effects in the catalytic evaluation of the bimetallic catalysts. The monometallic and bimetallic NPs revealed average sizes below 10 nm. The oxidation of benzyl alcohol with molecular oxygen as oxidant at mild conditions in liquid phase in the absence and presence (toluene or NaOH aqueous solution, 0.2 M) of a solvent was selected as test reaction to evaluate the catalytic properties of the above-mentioned solids. AuPd/Alumina exhibited the best catalytic activity among all bimetallic catalysts using toluene as solvent and under solvent-free conditions, respectively. In comparison to the monometallic catalysts, a synergistic effect with AuPd/Alumina was only evident in the solvent-free reaction. The AuPd/Alumina catalyst was able to oxidize benzyl alcohol selectively depending on the reaction medium into benzaldehyde (toluene or solvent-free) or benzoic acid (NaOH aqueous solution, 0.2 M). However, the catalyst deactivated due to particle growth of the bimetallic AuPd NPs by Ostwald ripening and leaching was not observed in the oxidation using toluene as solvent. The size of the catalytically active NPs, the metal composition of the particles, and the reaction conditions greatly influenced the catalytic oxidation results.Graphical Abstract.

  7. Evaluation of preservative effectiveness of gallic acid derivatives in aluminum hydroxide gel-USP

    Directory of Open Access Journals (Sweden)

    Anurag Khatkar

    2013-01-01

    Full Text Available Background: Preservatives are added to most of the pharmaceutical preparations to prevent them from deterioration throughout their shelf life. Literature reveals that the common synthetic preservatives have many limitations, such as development of microbial resistance (in due course of time and several serious side-effects. Aim: The aim of this study is to find out new preservatives synthesized from natural sources, which may have better efficiency than the existing synthetic preservatives. The derivatives of naturally occurring gallic acid were subjected for their preservative efficacy study. Their preservative efficiency was evaluated and compared with the standard parabens. Materials and Methods: The selected amide, anilide and ester derivatives of gallic acid were subjected to preservative efficacy testing in an official antacid preparation, {aluminum hydroxide gel-USP (United States Pharmacopoeia} against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus niger as representative challenging microorganisms as per USP 2004 guidelines. Results: The selected derivatives were found to be effective against all selected strains and showed preservative efficacy comparable to that of standard and even better in case E. coli, C. albicans and A. niger. The 8-hydroxy quinoline ester derivative showed better preservative efficacy than standard as well as other derivatives. Conclusion: The newly synthesized gallic acid preservatives were found to be effective in the proposed pharmaceutical preparation (Aluminium Hydroxide Gel - USP. Also, the synthesized preservatives have shown comparative and even better efficacy than the existing parabens and hence they have potential for use in pharmaceutical preparations.

  8. Semisynthesis, Characterization and Evaluation of New Adenosine Derivatives as Antiproliferative Agents

    Directory of Open Access Journals (Sweden)

    Francisco Valdés Zurita

    2018-05-01

    Full Text Available We describe the semisynthesis and biological effects of adenosine derivatives, which were anticipated to function as agonists for the A3 receptor. Molecular docking was used to select candidate compounds. Fifteen nucleoside derivatives were obtained through nucleophilic substitutions of the N6-position of the nucleoside precursor 6-chloropurine riboside by amines of different origin. All compounds were purified by column chromatography and further characterized by spectroscopic and spectrometric techniques, showing moderate yield. These molecules were then evaluated for their antiproliferative activity in human gastric cancer cells expressing the A3 receptor. We found that the compounds obtained have antiproliferative activity and that new structural modifications can enhance their biological activity. The ADME (Absorption, Distribution, Metabolism and Excretion properties of the most active compounds were also evaluated theoretically.

  9. Synthesis and biological evaluation of novel urea and thiourea derivatives of valacyclovir

    Directory of Open Access Journals (Sweden)

    Katla Ramana Venkata

    2014-01-01

    Full Text Available A series of novel urea and thiourea derivatives of valacyclovir were efficiently synthesized in high yields and evaluated their antiviral activity. 2-((6-Amino-4-oxo-4,5-dihydro-1H-imidazo[4,5-c]pyridin-1-ylmethoxyethyl-2-amino-3-ethylbutanoate (valacyclovir 1 is reacted with various aromatic isocyanates/thiocyanates 2 in the presence of N, N- dimethyl piperazine as a base in THF: pyridine (4:1 to obtain valacyclovir urea/thiourea derivatives 3(a-j. The structures of the title compounds 3(a-j were confirmed by IR, NMR (1H, 13C, mass spectral and elemental analysis. The newly synthesized compounds were screened for their antiviral activity against Tobacco mosaic virus (TMV and antioxidant activity was evaluated by DPPH, SOD and GST methods. The title compounds exhibited potent antiviral and good antioxidant activities.

  10. On The Effective Construction of Asymmetric Chudnovsky Multiplication Algorithms in Finite Fields Without Derivated Evaluation

    OpenAIRE

    Ballet, Stéphane; Baudru, Nicolas; Bonnecaze, Alexis; Tukumuli, Mila

    2016-01-01

    The Chudnovsky and Chudnovsky algorithm for the multiplication in extensions of finite fields provides a bilinear complexity which is uniformly linear whith respect to the degree of the extension. Recently, Randriambololona has generalized the method, allowing asymmetry in the interpolation procedure and leading to new upper bounds on the bilinear complexity. We describe the effective algorithm of this asymmetric method, without derivated evaluation. Finally, we give examples with the finite ...

  11. Evaluation of pulse oximeter derived photoplethysmographic signals for obstructive sleep apnea diagnosis

    OpenAIRE

    Li, Yan; Gao, He; Ma, Yan

    2017-01-01

    Abstract High prevalence of obstructive sleep apnea (OSA) has increased the demands for more convenient and accessible diagnostic devices other than standard in-lab polysomnography (PSG). Despite the increasing utility of photoplethysmograph (PPG), it remains understudied in underserved populations. This study aimed to evaluate the reliability of a standard pulse oximeter system with an automated analysis based on the PPG signal for the diagnosis of OSA, as compared with PSG derived measures....

  12. [Primary care evaluation of the hypertensive patient management in specialized care after derivation (DERIVA-2 Study)].

    Science.gov (United States)

    Martell-Claros, Nieves; Galgo Nafría, Alberto; Abad-Cardiel, María; Álvarez-Álvarez, Beatriz; García Donaire, José Antonio; Márquez-Contreras, Emilio; Molino-González, Ángel

    2017-10-13

    To know the opinion/evaluation of the primary care physicians (PCPH) of the received information about patients that were attended in specialized care (SC). Cross-sectional study. Performed nationwide in primary care centers. Researchers from the primary care network. We used the SEH-LELHA derivation criteria guidelines, plus an ad hoc survey that included demographic and anthropometric data, blood pressure levels, and the main reason for derivation to SC at the baseline and final (post-derivation) visit. In addition, time deployed for the study of every patient, changes in diagnosis and treatment, type of follow-up, issues throughout the derivation process and assessment of the medical referred to the PCPH were evaluated. With participation of 578 researchers from primary, the study included 1715 patients aged 60.7±13.3years, 62.7% male. Patients were taking 2.3±1.2 (range 0-10) antihypertensive drugs pre-referral and 2.5±1.2 (0-9) after derivation. Blood pressure levels changed from 166±21.6 /97.7±12.6mmHg to 143±14.4 /85.5±10.5mmHg. The number of controlled patients (BP<140 and <90mmHg) increased from 5.8% to 32.2%. Time between pre- and post-derivation visit was 72±64days (median 57days, IQ26-99). The PCPH received a medical report in 80.3% of cases, 76.9% with an explanation of the results of the complementary tests, 75.8% with additional information or a reasoning of treatment and in 71% of cases information about the patient future management. 63% of PCPH were fully agreed with the management of the specialist, 29% agree and 2% strongly disagree. The derivation was evaluated as effective or very effective in 86% of patients and no effective in 9%. Communication between AE and SC in HTA is valued satisfactorily by MAP. However there is still room for improvement in the process. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  13. Synthesis and antiproliferative activities of novel O-benzyl salicylamide derivatives

    Czech Academy of Sciences Publication Activity Database

    Dušek, J.; Imramovský, A.; Pauk, K.; Jorda, Radek; Řezníčková, Eva; Kryštof, Vladimír

    2017-01-01

    Roč. 14, č. 6 (2017), s. 662-671 ISSN 1570-1808 R&D Projects: GA ČR(CZ) GA15-15264S; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Amines * Antiproliferative activity * Cytotoxic activity * Pharmacological activity * Salicylamides Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Organic chemistry Impact factor: 1.170, year: 2016

  14. Synthesis and biological evaluation of novel heterocyclic derivatives of combretastatin A-4.

    Science.gov (United States)

    Nguyen, Thi Thanh Binh; Lomberget, Thierry; Tran, Ngoc Chau; Colomb, Evelyne; Nachtergaele, Lore; Thoret, Sylviane; Dubois, Joëlle; Guillaume, Joren; Abdayem, Rawad; Haftek, Marek; Barret, Roland

    2012-12-01

    A novel series of combretastatin A-4 heterocyclic analogues was prepared by replacement of the B ring with indole, benzofurane or benzothiophene, attached at the C2 position. These compounds were evaluated for their abilities to inhibit tubulin assembly: derivative cis3b, having a benzothiophene, showed an activity similar to those of colchicine or deoxypodophyllotoxine. The antiproliferative and antimitotic properties of cis3b against keratinocyte cancer cell lines were also evaluated and the intracellular organization of microtubules in the cells after treatment with both stereoisomers of 3b was also determined, using confocal microscopy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Evaluating measurement of dynamic constructs: defining a measurement model of derivatives.

    Science.gov (United States)

    Estabrook, Ryne

    2015-03-01

    While measurement evaluation has been embraced as an important step in psychological research, evaluating measurement structures with longitudinal data is fraught with limitations. This article defines and tests a measurement model of derivatives (MMOD), which is designed to assess the measurement structure of latent constructs both for analyses of between-person differences and for the analysis of change. Simulation results indicate that MMOD outperforms existing models for multivariate analysis and provides equivalent fit to data generation models. Additional simulations show MMOD capable of detecting differences in between-person and within-person factor structures. Model features, applications, and future directions are discussed. (c) 2015 APA, all rights reserved).

  16. Evaluation of next generation biomass derived fuels for the transport sector

    International Nuclear Information System (INIS)

    Tsita, Katerina G.; Pilavachi, Petros A.

    2013-01-01

    This paper evaluates next generation biomass derived fuels for the transport sector, employing the Analytic Hierarchy Process. Eight different alternatives of fuels are considered in this paper: bio-hydrogen, bio-synthetic natural gas, bio-dimethyl ether, bio-methanol, hydro thermal upgrading diesel, bio-ethanol, algal biofuel and electricity from biomass incineration. The evaluation of alternative fuels is performed according to various criteria that include economic, technical, social and policy aspects. In order to evaluate each alternative fuel, one base scenario and five alternative scenarios with different weight factors selection per criterion are presented. After deciding the alternative fuels’ scoring against each criterion and the criteria weights, their synthesis gives the overall score and ranking for all alternative scenarios. It is concluded that synthetic natural gas and electricity from biomass incineration are the most suitable next generation biomass derived fuels for the transport sector. -- Highlights: •Eight alternative fuels for the transport sector have been evaluated. •The method of the AHP was used. •The evaluation is performed according to economic, technical, social and policy criteria. •Bio-SNG and electricity from biomass incineration are the most suitable fuels

  17. Evaluation of the Precision of Satellite-Derived Sea Surface Temperature Fields

    Science.gov (United States)

    Wu, F.; Cornillon, P. C.; Guan, L.

    2016-02-01

    A great deal of attention has been focused on the temporal accuracy of satellite-derived sea surface temperature (SST) fields with little attention being given to their spatial precision. Specifically, the primary measure of the quality of SST fields has been the bias and variance of selected values minus co-located (in space and time) in situ values. Contributing values, determined by the location of the in situ values and the necessity that the satellite-derived values be cloud free, are generally widely separated in space and time hence provide little information related to the pixel-to-pixel uncertainty in the retrievals. But the main contribution to the uncertainty in satellite-derived SST retrievals relates to atmospheric contamination and because the spatial scales of atmospheric features are, in general, large compared with the pixel separation of modern infra-red sensors, the pixel-to-pixel uncertainty is often smaller than the accuracy determined from in situ match-ups. This makes selection of satellite-derived datasets for the study of submesoscale processes, for which the spatial structure of the upper ocean is significant, problematic. In this presentation we present a methodology to characterize the spatial precision of satellite-derived SST fields. The method is based on an examination of the high wavenumber tail of the 2-D spectrum of SST fields in the Sargasso Sea, a low energy region of the ocean close to the track of the MV Oleander, a container ship making weekly roundtrips between New York and Bermuda, with engine intake temperatures sampled every 75 m along track. Important spectral characteristics are the point at which the satellite-derived spectra separate from the Oleander spectra and the spectral slope following separation. In this presentation a number of high resolution 375 m to 10 km SST datasets are evaluated based on this approach.

  18. The effect of benzyl alcohol on pulsed laser polymerization of styrene and methylmethacrylate

    NARCIS (Netherlands)

    O'Driscoll, K.F.; Monteiro, M.J.; Klumperman, B.

    1997-01-01

    The homo- and copolymerizations of styrene (STY) and methylmethacrylate (MMA) have been studied in the presence of several levels of benzyl alcohol (BA). From pulsed laser polymerizations it has been found that the apparent propagation rate constant increased with increasing BA for all systems. In

  19. Design, synthesis and biological activity of novel peptidyl benzyl ketone FVIIa inhibitors

    DEFF Research Database (Denmark)

    Storgaard, Morten; Henriksen, Signe Teuber; Zaragoza, Florencio

    2011-01-01

    Herein is described the synthesis of a novel class of peptidyl FVIIa inhibitors having a C-terminal benzyl ketone group. This class is designed to be potentially suitable as stabilization agents of liquid formulations of rFVIIa, which is a serine protease used for the treatment of hemophilia...

  20. Homocoupling of benzyl halides catalyzed by POCOP-nickel pincer complexes

    KAUST Repository

    Chen, Tao

    2012-08-01

    Two types of POCOP-nickel(II) pincer complexes were prepared by mixing POCOP pincer ligands and NiX 2 in toluene at reflux. The resulting nickel complexes efficiently catalyze the homocoupling reactions of benzyl halides in the presence of zinc. The coupled products were obtained in excellent to quantitative yields. © 2012 Elsevier Ltd. All rights reserved.

  1. Synthesis, crystal structure and photophysical properties of (E)-4-(4-(2-hydroxybenzylideneamino)benzyl)oxazolidin-2-one

    International Nuclear Information System (INIS)

    Kumari, Rekha; Varghese, Anitha; George, Louis

    2016-01-01

    A new Schiff base, (4-(benzylideneamino)benzyl)oxazolidin-2-one has been synthesised from 4-(4-aminobenzyl)oxazolidin-2-one and salicylaldehyde by a simple condensation reaction. Single-crystal X-ray analysis of (E)-4-(4-(2-hydroxybenzylideneamino) benzyl)oxazolidin-2-one (HBOA) revealed that there is a 1-D, slipped, face-to-face motif with off-set, head-to-tail stacked columns. Detailed studies on photophysical properties of the synthesised compound in solutions indicate their potential applications in the field of organic light emitting devices and nonlinear optical materials. Absorption and fluorescence study of HBOA has been conducted in a series of solvents with increasing polarity at room temperature. Ground and excited state dipole moments have been determined experimentally by using Lippert–Mataga polarity function, Bakhshiev solvent polarity parameter, Kawskii–Chamma–Viallet solvent polarity parameter and RichardtГ—Віs microscopic solvent polarity parameter. Due to the considerable π-electron density redistribution, the excited state dipole moment was found to be larger than that of the ground state. The ground state dipole moment value was determined by quantum chemical method which was used to estimate excited state dipole moment through solvatochromic correlations. Kamlet–Taft and Catalan methods were used to get the information of both non-specific solute–solvent interactions and hydrogen bonding interactions. TD-DFT (B3LYP/6-311G(d,p)) has been used for the determination of HOMO–LUMO energies. Mulliken charges and Molecular electrostatic potential were also evaluated from DFT calculations.

  2. Curcumin inhibits adipogenesis induced by benzyl butyl phthalate in 3T3-L1 cells.

    Science.gov (United States)

    Sakuma, Satoru; Sumida, Maki; Endoh, Yukiko; Kurita, Ayaka; Yamaguchi, Ayana; Watanabe, Tomoki; Kohda, Tetsuya; Tsukiyama, Yui; Fujimoto, Yohko

    2017-08-15

    Phthalates are a group of endocrine disrupting chemicals and may have contributed to the recent global obesity health crisis. Increased adipogenesis via the peroxisome proliferator-activated receptor γ (PPARγ)-CCAAT-enhancer binding protein α (C/EBPα) pathway could be one critical mechanism responsible for phthalate-induced weight gain. On the other hand, curcumin has been shown to inhibit adipogenesis in cells and animal models. The present study was undertaken to evaluate, for the first time, whether curcumin could reduce adipogenesis induced by benzyl butyl phthalate (BBP) via downregulation of the PPARγ-C/EBPα pathway. 3T3-L1 preadipocytes were differentiated by treating them with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine in the presence of BBP, with or without curcumin. Cells that were grown in the presence of BBP alone showed a significant increase in triacylglycerol (TG) levels. In addition, the number of Oil Red O-stained cells and the mRNA expression levels of PPARγ, C/EBPα, adiponectin, and tumor necrosis factor-α (TNFα) were significantly increased. However, treatment with BBP in combination with curcumin resulted in major reductions in TG levels, the numbers of Oil Red O-stained cells, and the mRNA expression levels of the four proteins. These results suggest that curcumin might be an inhibitor of BBP-induced weight gain and inflammation via stimulation of adipocyte differentiation and TNFα generation. Curcumin may, therefore, be a potential medication for preventing the harmful effects of phthalates. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Synthesis and In Vitro Evaluation of New Thiosemicarbazone Derivatives as Potential Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Zafer Asım Kaplancıklı

    2016-01-01

    Full Text Available In an effort to develop potent antimicrobial agents, new thiosemicarbazone derivatives were synthesized via the reaction of 4-[4-(trifluoromethylphenyl]thiosemicarbazide with aromatic aldehydes. The compounds were evaluated for their inhibitory effects on pathogenic bacteria and yeasts using the CLSI broth microdilution method. Microplate Alamar Blue Assay was also carried out to determine the antimycobacterial activities of the compounds against Mycobacterium tuberculosis H37Rv. Among these derivatives, compounds 5 and 11 were more effective against Enterococcus faecalis (ATCC 29212 than chloramphenicol, whereas compounds 1, 2, and 12 and chloramphenicol showed the same level of antibacterial activity against E. faecalis. Moreover, compound 2 and chloramphenicol exhibited the same level of antibacterial activity against Staphylococcus aureus. On the other hand, the most potent anticandidal derivatives were found as compounds 2 and 5. These derivatives and ketoconazole exhibited the same level of antifungal activity against Candida glabrata. According to the Microplate Alamar Blue Assay, the tested compounds showed weak to moderate antitubercular activity.

  4. Synthesis and evaluation of 2-benzylidene-1-tetralone derivatives for monoamine oxidase inhibitory activity.

    Science.gov (United States)

    Amakali, Klaudia T; Legoabe, Lesetja Jan; Petzer, Anel; Petzer, Jacobus P

    2018-05-01

    Chalcone has been identified as a promising lead for the design of monoamine oxidase (MAO) inhibitors. This study attempted to discover potent and selective chalcone-derived MAO inhibitors by synthesising a series consisting of various cyclic chalcone derivatives. The cyclic chalcones were selected based on the possibility that their restricted structures would confer a higher degree of MAO isoform selectivity, and included the following chemical classes: 1-indanone, 1-tetralone, 1-benzosuberone, chromone, thiochromone, 4-chromanone and 4-thiochromanone. The results showed that the cyclic chalcones are in general good potency, and in most instances specific inhibitors of the human MAO-B isoform. Among these compounds, the 4-chromanone derivative was the most potent MAO-B inhibitor with an IC50 value of 0.156 µM. To further investigate the MAO inhibition of cyclic chalcones, a series of twenty-three 2-benzylidene-1-tetralone derivatives were synthesised and evaluated as MAO inhibitors. Most 2-benzylidene-1-tetralones possess good inhibitory activity and specificity for MAO-B with the most potent inhibitor displaying an IC50 value of 0.0064 µM, while the most potent MAO-A inhibitor possessed an IC50 value of 0.754 µM. This study thus shows that certain cyclic chalcones are human MAO-B inhibitors, compounds that could be suitable for the treatment of neurodegenerative disorders such as Parkinson's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Evaluation of pulse oximeter derived photoplethysmographic signals for obstructive sleep apnea diagnosis.

    Science.gov (United States)

    Li, Yan; Gao, He; Ma, Yan

    2017-05-01

    High prevalence of obstructive sleep apnea (OSA) has increased the demands for more convenient and accessible diagnostic devices other than standard in-lab polysomnography (PSG). Despite the increasing utility of photoplethysmograph (PPG), it remains understudied in underserved populations. This study aimed to evaluate the reliability of a standard pulse oximeter system with an automated analysis based on the PPG signal for the diagnosis of OSA, as compared with PSG derived measures.Consecutive out-patients with suspect OSA completed a PPG monitoring simultaneous with an overnight in-lab standard PSG. Forty-nine OSA patients (38 males, age 43.5 ± 16.9 years, BMI 26.9 ± 0.5 kg/m) were included in this study. Automated analyses were based on PPG and oximetry signals only. The PPG calculated measures were compared with PSG derived measures for agreement tests.Respiratory events index derived from PPG significantly correlated with PSG-derived apnea-hypopnea index (r = 0.935, P oximeter system with PPG recording can be used for the diagnosis or screening of OSA in high risk population.

  6. Synthesis and Evaluation of New Phthalazine Urea and Thiourea Derivatives as Carbonic Anhydrase Inhibitors

    Directory of Open Access Journals (Sweden)

    Nurcan Berber

    2013-01-01

    Full Text Available A new series of phthalazine substituted urea and thiourea derivatives were synthesized, and their inhibitory effects on the activity of purified human carbonic anhydrases (hCAs I and II were evaluated. 2H-Indazolo[2,1-b]phthalazine-trione derivative (1 was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and nitro group was reduced to amine derivative (2 with SnCl2·2H2O. The compound was reacted with isocyanates and isothiocyanates to get the final products (3a–p. The results showed that all the synthesized compounds inhibited the CA isoenzymes activity. 3a (IC50 = 6.40 µM for hCA I and 6.13 µM for hCA II has the most inhibitory effect. The synthesized compounds are very bulky to be able to bind near the zinc ion, and they much more probably bind as the coumarin derivatives.

  7. Silica functionalized Cu(II) acetylacetonate Schiff base complex: An efficient catalyst for the oxidative condensation reaction of benzyl alcohol with amines

    Science.gov (United States)

    Anbarasu, G.; Malathy, M.; Karthikeyan, P.; Rajavel, R.

    2017-09-01

    Silica functionalized Cu(II) acetylacetonate Schiff base complex via the one pot reaction of silica functionalized 3-aminopropyltriethoxysilane with acetyl acetone and copper acetate has been reported. The synthesized material was well characterized by analytical techniques such as FT-IR, UV-DRS, XRD, SEM-EDX, HR-TEM, EPR, ICP-AES and BET analysis. The characterization results confirmed the grafting of Cu(II) Schiff base complex on the silica surface. The catalytic activity of synthesized silica functionalized Cu(II) acetylacetonate Schiff base complex was evaluated through the oxidative condensation reaction of benzyl alcohol to imine.

  8. Histological and molecular evaluation of patient-derived colorectal cancer explants.

    Directory of Open Access Journals (Sweden)

    Joshua M Uronis

    Full Text Available Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.

  9. Synthesis and biological evaluation of new pyrazolo[3,4-d]pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Asma Agrebi

    2014-05-01

    Full Text Available Several new pyrazolopyrimidine compounds were achieved from aminocyanopyarazole 1. The starting material 1 was initially coupled with orthoester at refluxed with various primary amines, ammonia, hydrazines and hydroxylamine to furnish a series of pyrazolo[3,4-d]pyrimidines. The reaction of imidate 2a-b with hydrazide derivatives led to the formation of pyrazolo[3,4-d][1,2,4]triazolo[4,3-c]pyrimidines. Some of the synthesized compounds 3a and 4c were evaluated for their anti-inflammatory, antipyretic and nociceptive activities. We start by studing the toxicity of these two molecules by measuring the corresponding DL50. The DL50 of 3a and 4c are estimated to 1333.2mg / kg and 1593.5mg / kg respectively. Pharmacological evaluation showed that compounds 3a and 4c at doses (5.5-22.2 mg / Kg, i.p exhibited anti-inflammatory activities compared to Ibuprofen (150 mg / Kg, i.p, used as a refer ence drug. Further, our study showed that the injection of derived pyrazolopyrimidines on hyperthermic animal leads to a decrease in temperature after 1 hours of treatment compared to paracetamol used as reference. In addition, the injection of derived pyrazolopyrimidines at different doses contains a potent nociceptive activity. This effect is dose-dependent compared to aspirin.

  10. Antitumor and Antimicrobial Activity of Some Cyclic Tetrapeptides and Tripeptides Derived from Marine Bacteria

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    Subrata Chakraborty

    2015-05-01

    Full Text Available Marine derived cyclo(Gly-l-Ser-l-Pro-l-Glu was selected as a lead to evaluate antitumor-antibiotic activity. Histidine was chosen to replace the serine residue to form cyclo(Gly-l-His-l-Pro-l-Glu. Cyclic tetrapeptides (CtetPs were then synthesized using a solution phase method, and subjected to antitumor and antibiotic assays. The benzyl group protected CtetPs derivatives, showed better activity against antibiotic-resistant Staphylococcus aureus in the range of 60–120 μM. Benzyl group protected CtetPs 3 and 4, exhibited antitumor activity against several cell lines at a concentration of 80–108 μM. However, shortening the size of the ring to the cyclic tripeptide (CtriP scaffold, cyclo(Gly-l-Ser-l-Pro, cyclo(Ser-l-Pro-l-Glu and their analogues showed no antibiotic or antitumor activity. This phenomenon can be explained from their backbone structures.

  11. First Total Syntheses and Antimicrobial Evaluation of Penicimonoterpene, a Marine-Derived Monoterpenoid, and Its Various Derivatives

    Directory of Open Access Journals (Sweden)

    Jian-Chun Zhao

    2014-06-01

    Full Text Available The first total synthesis of marine-derived penicimonoterpene (±-1 has been achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction as the key step to construct the basic carbon skeleton. A total of 24 new derivatives of 1 have also been designed and synthesized. Their structures were characterized by analysis of their 1H NMR, 13C NMR and HRESIMS data. Some of them showed significant antibacterial activity against Aeromonas hydrophila, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, Vibrio anguillarum, V. harveyi and/or V. parahaemolyticus, and some showed activity against plant-pathogenic fungi (Alternaria brassicae, Colletotrichum gloeosporioides and/or Fusarium graminearum. Some of the derivatives exhibited antimicrobial MIC values ranging from 0.25 to 4 μg/mL, which were stronger than those of the positive control. Notably, Compounds 3b and 10 showed extremely high selectively against plant-pathogenic fungus F. graminearum (MIC 0.25 μg/mL and pathogenic bacteria E. coli (MIC 1 μg/mL, implying their potential as antimicrobial agents. SAR analysis of 1 and its derivatives indicated that modification of the carbon-carbon double bond at C-6/7, of groups on the allylic methylene unit and of the carbonyl group at C-1, effectively enhanced the antimicrobial activity.

  12. Clinical and morphological evaluation of snake venom derived fibrin glue on the tendon healing in dogs

    Directory of Open Access Journals (Sweden)

    G. C. Ferraro

    2005-12-01

    Full Text Available The aim of this study was to evaluate the effect of snake venom derived fibrin glue on the healing of the deep digital flexor tendon, during three periods. The tendon of the 2nd digit of 30 thoracic limbs of dogs was partially sectioned for glue application. Biopsies were performed 7, 15, and 30 days post surgery for the clinical and morphological study of tendons. Analysis of the results showed that 73.3% of the tendons showed stump retraction and 16.6% moderate to excessive adherence, which affected sliding. There was a significant difference in the number of inflammatory cells among the three studied periods, being the highest on day 15. The morphological analysis revealed a typical tendon healing process with a lower level of inflammation in the acute phase, facilitating the cicatricial maturation phase. Snake venom derived fibrin glue promotes the healing in dog flexor tendon.

  13. Synthesis and decreasing Aβ content evaluation of arctigenin-4-yl carbamate derivatives.

    Science.gov (United States)

    Xu, Xingyu; Li, Cong; Lei, Min; Zhu, Zhiyuan; Yan, Jianming; Shen, Xu; Hu, Lihong

    2016-07-01

    A series of arctigenin-4-yl carbamate derivatives were synthesized and evaluated for potency in reducing β-amyloid (Aβ) content in HEK293-APPswe cells. Most of the arctigenin-4-yl aralkyl or aryl carbamate derivatives showed improved potency in reducing Aβ content. Among the synthesized compounds, arctigenin-4-yl (3-chlorophenyl)carbamate (20) exhibited the strongest potency with 78.7% Aβ content reduction at 20μM. Furthermore, the effect of arctigenin-4-yl (4-chlorophenyl)carbamate (19) and arctigenin-4-yl (3-chlorophenyl)carbamate (20) on lowing Aβ content was better than arctigenin under the concentrations of 1, 10 and 20μM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Design, Synthesis and Biological Evaluation of C(6-Modified Celastrol Derivatives as Potential Antitumor Agents

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    Kaiyong Tang

    2014-07-01

    Full Text Available New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468. The results showed that most of the compounds displayed potent inhibition against BGC823, H4, and Bel7402, with IC50s of 1.84–0.39 μM. The best compound NST001A was tested in an in vivo antitumor assay on nude mice bearing Colo 205 xenografts, and showed significant inhibition of tumor growth at low concentrations. Therefore, celastrol C-6 derivatives are potential drug candidates for treating cancer.

  15. Design, Synthesis and Evaluation of Ribose-modified Anilinopyrimidine Derivatives as EGFR Tyrosine Kinase Inhibitors

    Science.gov (United States)

    Hu, Xiuqin; Wang, Disha; Tong, Yi; Tong, Linjiang; Wang, Xia; Zhu, Lili; Xie, Hua; Li, Shiliang; Yang, You; Xu, Yufang

    2017-11-01

    The synthesis of a series of ribose-modified anilinopyrimidine derivatives was efficiently achieved by utilizing DBU or tBuOLi-promoted coupling of ribosyl alcohols with 2,4,5-trichloropyrimidine as key step. Preliminary biological evaluation of this type of compounds as new EGFR tyrosine kinase inhibitors for combating EGFR L858R/T790M mutant associated with drug resistance in the treatment of non-small cell lung cancer revealed that 3-N-acryloyl-5-O-anilinopyrimidine ribose derivative 1a possessed potent and specific inhibitory activity against EGFR L858R/T790M over WT EGFR. Based upon molecular docking studies of the binding mode between compound 1a and EGFR, the distance between the Michael receptor and the pyrimidine scaffold is considered as an important factor for the inhibitory potency and future design of selective EGFR tyrosine kinase inhibitors against EGFR L858R/T790M mutants.

  16. Design, Synthesis and Biological Evaluation of Benzohydrazide Derivatives Containing Dihydropyrazoles as Potential EGFR Kinase Inhibitors

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    Hai-Chao Wang

    2016-08-01

    Full Text Available A series of novel benzohydrazide derivatives containing dihydropyrazoles have been synthesized as potential epidermal growth factor receptor (EGFR kinase inhibitors and their biological activities as potential antiproliferative agents have been evaluated. Among these compounds, compound H20 exhibited the most potent antiproliferative activity against four cancer cell line variants (A549, MCF-7, HeLa, HepG2 with IC50 values of 0.46, 0.29, 0.15 and 0.21 μM respectively, which showed the most potent EGFR inhibition activities (IC50 = 0.08 μM for EGFR. Molecular modeling simulation studies were performed in order to predict the biological activity and activity relationship (SAR of these benzohydrazide derivatives. These results suggested that compound H20 may be a promising anticancer agent.

  17. New 1,3-benzodioxole derivatives: Synthesis, evaluation of in vitro schistosomicidal activity and ultrastructural analysis.

    Science.gov (United States)

    Mariz Gomes da Silva, Luana Maria; de Oliveira, Jamerson Ferreira; Silva, Willams Leal; da Silva, Anekecia Lauro; de Almeida Junior, Antônio Sérgio Alves; Barbosa Dos Santos, Victor Hugo; Alves, Luiz Carlos; Brayner Dos Santos, Fábio André; Costa, Vlaudia Maria Assis; Aires, André de Lima; de Lima, Maria do Carmo Alves; Albuquerque, Monica Camelo Pessoa de Azevedo

    2018-03-01

    Schistosomiasis is considered a serious public health problem in 78 countries and territories located in Africa, Asia and America and it is estimated in more than 249 million people infected by any of the species of Schistosoma. The exclusive use of praziquantel (PZQ), effective drug against all species of Schistosoma, has been the basis of the development of a possible resistance against the strains of this parasite. In addition, PZQ is not effective against young forms of worms. Thus, there is a need for the development of new drugs with schistosomicidal activity. The objective of this work was to synthesize and to evaluate the therapeutic potential of new benzodioxole derivatives (3-14) candidates for schistosomicidal drugs. All compounds synthesized showed in vitro schistosomicidal activity. The derivative 12 was considered the best compound, since it took 100% of worms to mortality in the first 72 h of exposure at the concentration of 100 μM and 83.3% at the concentration of 50 μM. Furthermore, male and female adult worms, incubated for 24 h with the compound 12 showed tegument damages characterized by extensive desquamation and edema, tuber destruction, bubble formation and exposure of the muscle layer. This compound has a restricted structure, where the thiazolidinone is attached to the 4-position of the 1,3-benzodioxol ring. The structural conformation of derivative 12 was probably responsible for the promising schistosomicidal activity, where the presence of an electron/conformational restriction of the thiazolidine ring, as well as the action of bromine as a bulk substitute, favored an increase in biological activity. In addition, tegumentary changes caused by derivative 12 may also have been responsible for the death of adult worms of Schistosoma mansoni. Therefore, we verified that the results obtained in this study make benzodioxole derivatives possible candidates for prototypes of new schistosomicidal drugs. Copyright © 2018 Elsevier B

  18. Evaluation of 18F-labeled icotinib derivatives as potential PET agents for tumor imaging

    International Nuclear Information System (INIS)

    Hongyu Ren; Hongyu Ning; Jin Chang; Mingxia Zhao; Yong He; Yan Chong; Chuanmin Qi

    2016-01-01

    In this study, three 18 F-labeled crown ether fused anilinoquinazoline derivatives ([ 18 F]11a-c) were synthesized and evaluated as potential tumor imaging probes. The biodistribution results of [ 18 F]11b were good. Compared with [ 18 F]-fludeoxyglucose and l-[ 18 F]-fluoroethyltyrosine in the same animal model, [ 18 F]11b had better tumor/brain, tumor/muscle, and tumor/blood uptake ratios. Overall, these results suggest that [ 18 F]11b is promising as a tumor imaging agent for positron emission tomography. (author)

  19. Preclinical evaluation of carbon-11 and fluorine-18 sulfonamide derivatives for in vivo radiolabeling of erythrocytes

    OpenAIRE

    Gheysens, Olivier; Akurathi, Vamsidhar; Chekol, Rufael; Dresselaers, Tom; Celen, Sofie; Koole, Michel; Dauwe, Dieter; Cleynhens, Bernard J; Claus, Piet; Janssens, Stefan; Verbruggen, Alfons M; Nuyts, Johan; Himmelreich, Uwe; Bormans, Guy M

    2013-01-01

    Background To date, few PET tracers for in vivo labeling of red blood cells (RBCs) are available. In this study, we report the radiosynthesis and in vitro and in vivo evaluation of 11C and 18F sulfonamide derivatives targeting carbonic anhydrase II (CA II), a metallo-enzyme expressed in RBCs, as potential blood pool tracers. A proof-of-concept in vivo imaging study was performed to demonstrate the feasibility to assess cardiac function and volumes using electrocardiogram (ECG)-gated positron ...

  20. Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads

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    Yi Bi

    2017-04-01

    Full Text Available Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20(S-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300 and Gram-negative bacteria (P. aer PAO1 and A. baum ATCC19606 in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC value of 2–16 µg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL and kanamycin (KAN (FICI < 0.5. Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity.

  1. SYNTHESIS AND EVALUATION OF NEW PHTHALAZINE SUBSTITUTED β-LACTAM DERIVATIVES AS CARBONIC ANHYDRASE INHIBITORS.

    Science.gov (United States)

    Berber, Nurcan; Arslan, Mustafa; Bilen, Çiğdem; Sackes, Zübeyde; Gençer, Nahit; Arslan, Oktay

    2015-01-01

    A new series of phthalazine substituted β-lactam derivatives were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase (hCA I and II) were evaluated. 2H-Indazolo[2,1-b]phthala- zine-trione derivative was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and the nitro group was reduced to 13-(4-aminophenyl)-3,3-dimethyl-3,4-dihydro- 2H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione with SnCl2 · 2H2O. The reduced compound was re- acted with different aromatic aldehydes, and phthalazine substituted imines were synthesized. The imine compounds undergo (2+2) cycloaddition reactions with ketenes to produce 2H-indazolo[2,1-b]phthala-zine-trione substituted β-lactam derivatives. The β-lactam compounds were tested as inhibitors of the CA isoenzyme activity. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. 1-(4-(3,3-dimethyl- 1,6,1 1-trioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2-b]phthalazin-13- yl)phenyl)-2-oxo-4-p-tolylazetidin-3-yl acetate (IC50 = 6.97 µM for hCA I and 8.48 µM for hCA II) had the most inhibitory effect.

  2. Synthesis and biological evaluation of lycorine derivatives as dual inhibitors of human acetylcholinesterase and butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Wang Yue-Hu

    2012-09-01

    Full Text Available Abstract Background Alzheimer’s disease (AD is a neurologically degenerative disorder that affects more than 20 million people worldwide. The selective butyrylcholinesterase (BChE inhibitors and bivalent cholinesterase (ChE inhibitors represent new treatments for AD. Findings A series of lycorine derivatives (1–10 were synthesized and evaluated for anti-cholinesterase activity. Result showed that the novel compound 2-O-tert-butyldimethylsilyl-1-O-(methylthiomethyllycorine (7 was a dual inhibitor of human acetylcholinesterase (hAChE and butyrylcholinesterase (hBChE with IC50 values of 11.40 ± 0.66 μM and 4.17 ± 0.29 μM, respectively. The structure-activity relationships indicated that (i the 1-O-(methylthiomethyl substituent in lycorine was better than the 1-O-acetyl group for the inhibition of cholinesterase; (ii the acylated or etherified derivatives of lycorine and lycorin-2-one were more potent against hBChE than hAChE; and (iii the oxidation of lycorine at C-2 decreases the activity. Conclusion Acylated or etherified derivatives of lycorine are potential dual inhibitors of hBChE and hAChE. Hence, further study on the modification of lycorine for ChE inhibition is necessary.

  3. Differentiation, Evaluation, and Application of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells.

    Science.gov (United States)

    Lin, Yang; Gil, Chang-Hyun; Yoder, Mervin C

    2017-11-01

    The emergence of induced pluripotent stem cell (iPSC) technology paves the way to generate large numbers of patient-specific endothelial cells (ECs) that can be potentially delivered for regenerative medicine in patients with cardiovascular disease. In the last decade, numerous protocols that differentiate EC from iPSC have been developed by many groups. In this review, we will discuss several common strategies that have been optimized for human iPSC-EC differentiation and subsequent studies that have evaluated the potential of human iPSC-EC as a cell therapy or as a tool in disease modeling. In addition, we will emphasize the importance of using in vivo vessel-forming ability and in vitro clonogenic colony-forming potential as a gold standard with which to evaluate the quality of human iPSC-EC derived from various protocols. © 2017 American Heart Association, Inc.

  4. Haenamindole, an unusual diketopiperazine derivative from a marine-derived Penicillium sp. KCB12F005.

    Science.gov (United States)

    Kim, Jong Won; Ko, Sung-Kyun; Son, Sangkeun; Shin, Kee-Sun; Ryoo, In-Ja; Hong, Young-Soo; Oh, Hyuncheol; Hwang, Bang Yeon; Hirota, Hiroshi; Takahashi, Shunji; Kim, Bo Yeon; Osada, Hiroyuki; Jang, Jae-Hyuk; Ahn, Jong Seog

    2015-11-15

    During the chemical investigation of marine-derived fungus, an unusual diketopiperazine (DKP) alkaloid, haenamindole (1), was isolated from a culture of the marine-derived fungus Penicillium sp. KCB12F005. The structure of 1, which possesses benzyl-hydroxypiperazindione and phenyl-pyrimidoindole rings system in the molecule, was elucidated by analysis of NMR and MS data. The stereochemistry of 1 was determined by ROESY and advanced Marfey's method. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Solid-state conformation of copolymers of ß-benzyl-L-aspartate with L-alanine, L-leucine, L-valine, γ-benzyl-L-glutamate, or ε-carbobenzoxy-L-lysine

    NARCIS (Netherlands)

    Sederel, Willem L.; Bantjes, Adriaan; Feijen, Jan; Anderson, James M.

    1980-01-01

    The solid-state conformation of copolymers of ß-benzyl-L-aspartate [L-Asp(OBzl)] with L-leucine (L-Leu), L-alanine (L-Ala), L-valine (L-Val), γ-benzyl-L-glutamate [L-Glu(OBzl)], or ε-carbobenzoxy-L-lysine (Cbz-L-Lys) has been studied by ir spectroscopy and circular dichroism (CD). The ir spectra in

  6. The Evaluation and Utilization of Marine-derived Bioactive Compounds with Anti-obesity Effect.

    Science.gov (United States)

    Jin, Qiu; Yu, Huahua; Li, Pengcheng

    2018-01-01

    Obesity is a global epidemic throughout the world. There is thus increasing interest in searching for natural bioactive compounds with anti-obesity effect. A number of marine compounds have been regarded as potential sources of bioactive compounds and are associated with an anti-obesity effect. Marine-derived compounds with anti-obesity effect and their current applications, methods and indicators for the evaluation of anti-obesity activity are summarized in this review. in order to make contributions to the development of marine-derived functional food against obesity. In this review, an overview of marine-derived compounds with anti-obesity effect, including marine polysaccharides, marine lipid, marine peptides, marine carotenoids is intensively made with an emphasis on their efficacy and mechanism of action. Meanwhile, methods and indicators for the evaluation of anti-obesity activity are discussed. We summarize these methods into three categories: in vitro assay (including adsorption experiments and enzyme inhibitory assay), cell line study, animal experiments and clinical experiments. In addition, a brief introduction of the current applications of marine bioactive compounds with anti-obesity activity is discussed. Marine environment is a rich source of both biological and chemical diversity. In the past decades, numerous novel compounds with anti-obesity activity have been obtained from marine organisms, and many of them have been applied to industrial production such as functional foods and pharmaceuticals. Further studies are needed to explore the above-mentioned facts. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Spin-Center Shift-Enabled Direct Enantioselective α-Benzylation of Aldehydes with Alcohols.

    Science.gov (United States)

    Nacsa, Eric D; MacMillan, David W C

    2018-03-07

    Nature routinely engages alcohols as leaving groups, as DNA biosynthesis relies on the removal of water from ribonucleoside diphosphates by a radical-mediated "spin-center shift" (SCS) mechanism. Alcohols, however, remain underused as alkylating agents in synthetic chemistry due to their low reactivity in two-electron pathways. We report herein an enantioselective α-benzylation of aldehydes using alcohols as alkylating agents based on the mechanistic principle of spin-center shift. This strategy harnesses the dual activation modes of photoredox and organocatalysis, engaging the alcohol by SCS and capturing the resulting benzylic radical with a catalytically generated enamine. Mechanistic studies provide evidence for SCS as a key elementary step, identify the origins of competing reactions, and enable improvements in chemoselectivity by rational photocatalyst design.

  8. Bis(1-benzyl-1H-benzimidazole-κN3dichloridozinc

    Directory of Open Access Journals (Sweden)

    Rachid Bouhfid

    2014-03-01

    Full Text Available In the title compound, [ZnCl2(C14H12N22], the ZnII atom exhibits a distorted tetrahedral coordination geometry involving two chloride anions and two N-atom donors from 1-benzyl-1H-benzimidazole ligands. In both ligands, the benzyl and benzimidazole rings are nearly perpendicular [dihedral angles = 81.7 (2 and 81.5 (2°]. The two benzimidazole systems are essentially planar [maximum deviations = 0.015 (3 and 0.020 (2 Å] and form a dihedral angle of 78.09 (8°. In the crystal, centrosymmetrically related molecules are linked by pairs of C—H...Cl hydrogen bonds into chains parallel to the a axis.

  9. Synthesis and Properties of Shape Memory Poly(γ-Benzyl-l-Glutamate-b-Poly(Propylene Glycol-b-Poly(γ-Benzyl-l-Glutamate

    Directory of Open Access Journals (Sweden)

    Lin Gu

    2017-12-01

    Full Text Available Shape memory polymers (SMPs have attracted much attention as an important class of stimuli-responsive materials for biomedical applications. For SMP-based biomaterials, in addition to suitable shape recovery performances, their mechanical properties, biodegradability, biocompatibility, and sterilizability needs to be considered. Polypeptides can satisfy the requirements outlined above. However, there are few reports on shape memory polypeptides. In this paper, shape memory poly(γ-benzyl-l-glutamate (PBLG-PPG-PBLG was synthesized by ring-opening polymerization of γ-benzyl-l-glutamate-N-carboxyanhydrides (BLG-NCA with poly(propylene glycol bis(2-aminopropyl ether as the macroinitiator. 1H Nuclear Magnetic Resonance (NMR and Fourier-Transform Infrared Spectroscopy (FTIR were used to characterize the structure of the obtained PBLG-PPG-PBLG. The FTIR analysis showed that PBLG-PPG-PBLG has α-helical and β-sheet structures. PBLG-PPG-PBLG has good shape memory properties, its shape recovery time is less than 120 s, and its shape recovery rate is 100%. In this study, we reported a simple synthetic method to obtain intelligent polypeptide materials, which will be used in many biomedical applications.

  10. Alkylation of pyridines at their 4-positions with styrenes plus yttrium reagent or benzyl Grignard reagents.

    Science.gov (United States)

    Mizumori, Tomoya; Hata, Takeshi; Urabe, Hirokazu

    2015-01-02

    A new regioselective alkylation of pyridines at their 4-position was achieved with styrenes in the presence of yttrium trichloride, BuLi, and diisobutylaluminium hydride (DIBAL-H) in THF. Alternatively, similar products were more simply prepared from pyridines and benzyl Grignard reagents. These reactions are not only a useful preparation of 4-substituted pyridines but are also complementary to other relevant reactions usually giving 2-substituted pyridines. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Use of cyclodextrins as a cosmetic delivery system for fragrance materials: linalool and benzyl acetate.

    Science.gov (United States)

    Numanoğlu, Ulya; Sen, Tangül; Tarimci, Nilüfer; Kartal, Murat; Koo, Otilia M Y; Onyüksel, Hayat

    2007-10-19

    The aim of this study was to increase the stability and water solubility of fragrance materials, to provide controlled release of these compounds, and to convert these substances from liquid to powder form by preparing their inclusion complexes with cyclodextrins (CDs). For this purpose, linalool and benzyl acetate were chosen as the fragrance materials. The use of beta-cyclodextrin (beta CD) and 2-hydroxypropyl-beta-cyclodextrin (2-HP beta CD) for increasing the solubility of these 2 fragrance materials was studied. Linalool and benzyl acetate gave a B-type diagram with beta CD, whereas they gave an A(L)-type diagram with 2-HP beta CD. Therefore, complexes of fragrance materials with 2-HP beta CD at 1:1 and 1:2 molar ratios (guest:host) were prepared. The formation of inclusion complexes was confirmed using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy and circular dichroism spectroscopy. The results of the solubility studies showed that preparing the inclusion complex with 2-HP beta CD at a 1:1 molar ratio increased the solubility of linalool 5.9-fold and that of benzyl acetate 4.2-fold, whereas the complexes at a 1:2 molar ratio increased the solubility 6.4- and 4.5-fold for linalool and benzyl acetate, respectively. The stability and in vitro release studies were performed on the gel formulations prepared using uncomplexed fragrance materials or inclusion complexes of fragrance materials at a 1:1 molar ratio. It was observed that the volatility of both fragrance materials was decreased by preparing the inclusion complexes with 2-HP beta CD. Also, in vitro release data indicated that controlled release of fragrances could be possible if inclusion complexes were prepared.

  12. Substitution Effects and Linear Free Energy Relationships During Reduction of 4- Benzoyl-n-(4-substituted Benzyl)pyridinium Cations

    Science.gov (United States)

    Leventis, Nicholas; Zhang, Guo-Hui; Rawashdeh, Abdel-Monem M.; Sotiriou-Leventis, Chariklia; Gray, Hugh R. (Technical Monitor)

    2003-01-01

    In analogy to 4-(para-substituted benzoyl)-N-methylpyridinium cations (1-X's), the title species (2-X's, -X = -OCH3, -CH3, -H, -Br, -COCH3, -NO2) undergo two reversible, well-separated (E(sub 1/2) greater than or equal to 650 mV) one-electron reductions. The effect of substitution on the reduction potentials of 2-X's is much weaker than the effect of the same substituents on 1-X's: the Hammett rho-values are 0.80 and 0.93 for the 1st- and 2nd-e reduction of 2-X's vs. 2.3 and 3.3 for the same reductions of 1-X's, respectively. Importantly, the nitro group of 2-NO2 undergoes reduction before the 2nd-e reduction of the 4-benzoylpyridinium system. These results suggest that the redox potentials of the 4-benzoylpyridinium system can be course-tuned via p-benzoyl substitution and fine-tuned via para-benzyl substitution. Introducing the recently derived substituent constant of the -NO2(sup)- group (sigma para-NO2(sup)- = -0.97) yields an excellent correlation for the 3rd-e reduction of 2- NO2 (corresponding to the reduction of the carbonyl group) with the 2nd-e reduction of the other 2-X's, and confirms the electron donating properties of -NO2(sup)-.

  13. Evaluation of 8-Hydroxyquinoline Derivatives as Hits for Antifungal Drug Design.

    Science.gov (United States)

    Pippi, Bruna; Reginatto, Paula; Machado, Gabriella da Rosa Monte; Bergamo, Vanessa Zafaneli; Lana, Daiane Flores Dalla; Teixeira, Mario Lettieri; Franco, Lucas Lopardi; Alves, Ricardo José; Andrade, Saulo Fernandes; Fuentefria, Alexandre Meneghello

    2017-10-01

    Clioquinol is an 8-hydroxyquinoline derivative that was widely used from the 1950s to 1970s as an oral antiparasitic agent. In 1970, the oral forms were withdrawn from the market due to reports of toxicity, but topical formulations for antifungal treatment remained available. Thus, the purpose of this study was to evaluate the toxicity, anti-Candida and antidermatophyte activity and to determine pharmacodynamic characteristics of clioquinol and other 8-hydroxyquinoline derivatives (8-hydroxy-5-quinolinesulfonic acid and 8-hydroxy-7-iodo-5-quinolinesulfonic acid). Antifungal activity was tested by broth microdilution and the fungicidal or fungistatic effect was checked by a time-kill assay. Permeation and histopathological evaluation were performed in Franz diffusion cells with ear skin of pigs and examined under light microscopy. An HET-CAM test was used to determine the potential irritancy. The three compounds were active against all isolates showing anti-Candida and antidermatophyte activity, with MIC ranges of 0.031-2 μg/ml, 1-512 μg/ml, and 2-1024 μg/ml for clioquinol, 8-hydroxy-5-quinolinesulfonic acid, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid, respectively. All compounds showed fungistatic effect for Candida, 8-hydroxy-5-quinolinesulfonic acid, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid showed a fungicidal effect for M. canis and T. mentagrophytes, and clioquinol showed a fungicidal effect only for T. mentagrophytes. Furthermore, they presented a fungicidal effect depending on the time and concentration. The absence of lesions was observed in histopathological evaluation and no compound was irritating. Moreover, clioquinol and 8-hydroxy-5-quinolinesulfonic acid accumulated in the epithelial tissue, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid had a high degree of permeation. In conclusion, 8-hydroxyquinoline derivatives showed antifungal activity and 8-hydroxy-5-quinolinesulfonic acid demonstrated the potential for antifungal drug design.

  14. Effect of gamma-irradiation on the plasticization of nylon 6 with benzyl alcohol

    International Nuclear Information System (INIS)

    Jamdagni, R.P.; Chaudhuri, N.K.

    1980-01-01

    The effect of γ-irradiation on the plasticization of nylon 6 monofilaments with benzyl alcohol by monitoring the glass transition temperature Tg after γ-irradiation has been studied. The method applied for determining the Tg is thermomechanical. The longitudinal deformation was determined with nylon 6 monofilaments immersed in benzyl alcohol, carrying a negligible weight to keep it taut. The temperature was varied in the range 3deg - 90deg C. Samples were prepared at different irradiation doses between 0 and 16 Mrad using a Cobalt-60 source. At each irradiation dose, a percentage extension vs temperature plot was made from the data obtained, and the Tg of the irradiated filament was determined from this plot. It was observed that the Tg started increasing very slowly upto 4 Mrad. The rate is appreciably faster after 8 Mrad. At 16 Mrad the Tg rises from its value in unirradiated nylon 6 monofilaments plasticized with benzyl alcohol, that is, the control, by about 13deg C. This upward shift of Tg is an antiplasticization effect and is accompanied with change of other mechanical properties, such as extensibility and tensile strength. The paper discusses the implication of these results in terms of previously known behaviour of scission and crosslinking due to γ-irradiation in nylon 6 and explores the possibility of application of the effect in processing. (author)

  15. Ytterbia doped nickel–manganese mixed oxide catalysts for liquid phase oxidation of benzyl alcohol

    Directory of Open Access Journals (Sweden)

    S.S.P. Sultana

    2017-11-01

    Full Text Available Nickel–manganese mixed oxides doped with 1, 3, 5 mol% ytterbia have been prepared by co-precipitation method and used in the catalytic oxidation of benzyl alcohol. Catalytic activity of these oxides calcined at 400 °C and 500 °C was studied for selective oxidation of benzyl alcohol to the corresponding aldehyde using molecular oxygen as an oxidizing agent. The results showed that thermally stable 5 mol% ytterbia doped nickel–manganese oxide [Yb2O3-(5%-Ni6MnO8] exhibited highest catalytic performance when it was calcined at 400 °C. A 100% conversion of the benzyl alcohol was achieved with >99% selectivity to benzaldehyde within a reaction period of 5 h at 100 °C. The mixed oxide prepared has been characterized by scanning election microscopy (SEM and energy dispersive X-ray analysis (EDXA, X-ray diffraction (XRD, Fourier transform infrared spectroscopy (FT-IR, thermogravimetric analysis (TGA, Brunauer–Emmett–Teller (BET and temperature programed reduction (H2-TPR.

  16. Mechanisms of catalytic cleavage of benzyl phenyl ether in aqueous and apolar phases

    Energy Technology Data Exchange (ETDEWEB)

    He, Jiayue; Lu, Lu; Zhao, Chen; Mei, Donghai; Lercher, Johannes A.

    2014-03-01

    Catalytic pathways for the cleavage of ether bonds in benzyl phenyl ether (BPE) in liquid phase using Ni- and zeolite-based catalysts are explored. In the absence of catalysts, the C-O bond is selectively cleaved in water by hydrolysis, forming phenol and benzyl alcohol as intermediates, followed by alkylation. The hydronium ions catalyzing the reactions are provided by the dissociation of water at 523 K. Upon addition of HZSM-5, rates of hydrolysis and alkylation are markedly increased in relation to proton concentrations. In the presence of Ni/SiO2, the selective hydrogenolysis dominates for cleaving the Caliphatic-O bond. Catalyzed by the dual-functional Ni/HZSM-5, hydrogenolysis occurs as the major route rather than hydrolysis (minor route). In apolar undecane, the non-catalytic thermal pyrolysis route dominates. Hydrogenolysis of BPE appears to be the major reaction pathway in undecane in the presence of Ni/SiO2 or Ni/HZSM-5, almost completely suppressing radical reactions. Density functional theory (DFT) calculations strongly support the proposed C-O bond cleavage mechanisms on BPE in aqueous and apolar phases. These calculations show that BPE is initially protonated and subsequently hydrolyzed in the aqueous phase. Finally, DFT calculations suggest that the radical reactions in non-polar solvents lead to primary benzyl and phenoxy radicals in undecane, which leads to heavier condensation products as long as metals are absent for providing dissociated hydrogen.

  17. Synthesis, Characterization, and Nonlinear Optical Properties of P-Substituted Poly Gamma-Benzyl

    Science.gov (United States)

    Choi, Dong-Hoon

    Poly gamma-benzyl-L-glutamate (PBLG), poly gamma-p-fluorobenzyl -L-glutamate (PGLU(pFB)), poly gamma -p-nitrobenzyl-L-glutamate (PGLU(pNB)), and poly gamma-p-trifluoromethylbenzyl-L-glutamate (PGLU(pTFMB)) have been synthesized. These PBLG polymers show variations in the side chain conformations in the solid state and solution state. In the solid state, the side chain orientation was assigned to a longitudinal or transverse direction by virtue of the polarized infrared spectrum of each PBLG analogue. The characteristics of the lyotropic liquid crystalline behavior could be observed. The optical waveguiding property of these polymers facilitated measurement of the refractive index and the thickness of each polymer film. Poling the polymer films and using the simple reflection technique, the electro -optic coefficients of the PBLG analogues could be determined. The effect of the para substitution on benzyl ester as it effected the electro-optic coefficient and the relation between the dielectric properties and the electro-optic effect of each polymer were investigated. These studies were able to demonstrate which conformation of the side chain in para substituted poly gamma-benzyl -L-glutamates is a more favorable conformation for enhancing the electro-optic behavior of these polymers.

  18. Synthesis and Biological Evaluation of Apigenin Derivatives as Antibacterial and Antiproliferative Agents

    Directory of Open Access Journals (Sweden)

    Jinyi Wang

    2013-09-01

    Full Text Available Two series of apigenin [5,7-dihydroxy-2-(4-hydroxyphenyl-4H-chromen-4-one] derivatives, 3a–3j and 4a–4j, were synthesized. The apigenin and alkyl amines moieties of these compounds were separated by C2 or C3 spacers, respectively. The chemical structures of the apigenin derivatives were confirmed using 1H-NMR, 13C-NMR, and electrospray ionization mass spectroscopy. The in vitro antibacterial and antiproliferative activities of all synthesized compounds were determined. Among the tested compounds, 4a–4j displayed significant antibacterial activity against the tested strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. Additionally, 4i showed the best inhibitory activity with minimum inhibitory concentrations of 1.95, 3.91, 3.91, and 3.91 μg/mL against S. aureus, B. subtilis, E. coli, and P. aeruginosa, respectively. The antiproliferative activity of the apigenin derivatives was evaluated by an MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide] assay. We determined that 4a–4j displayed better growth inhibition activity against four human cancer cell lines, namely, human lung (A549, human cervical (HeLa, human hepatocellular liver (HepG2, and human breast (MCF-7 cancer cells, than the parent apigenin. Compound 4j was found to be the most active antiproliferative compound against the selected cancer cells. Structure-activity relationships were also discussed based on the obtained experimental data.

  19. Disubstituted thiourea derivatives and their activity on CNS: synthesis and biological evaluation.

    Science.gov (United States)

    Stefanska, Joanna; Szulczyk, Daniel; Koziol, Anna E; Miroslaw, Barbara; Kedzierska, Ewa; Fidecka, Sylwia; Busonera, Bernardetta; Sanna, Giuseppina; Giliberti, Gabriele; La Colla, Paolo; Struga, Marta

    2012-09-01

    A series of new thiourea derivatives of 1,2,4-triazole have been synthesized. The difference in structures of obtained compounds are directly connected with the kind of isothiocyanate (aryl/alkyl). The (1)H NMR, (13)C NMR, MS methods were used to confirm structures of obtained thiourea derivatives. The molecular structure of (1, 17) was determined by an X-ray analysis. Two of the new compounds (8 and 14) were tested for their pharmacological activity on animal central nervous system (CNS) in behavioural animal tests. The results presented in this work indicate the possible involvement of the serotonergic system in the activity of 8 and 14. In the case of 14 is also a possible link between its activity and the endogenous opioid system. All obtained compounds were tested for antibacterial activity against gram-positive cocci, gram-negative rods and antifungal activity. Compounds (1, 2, 5, 7, 9) showed significant inhibition against gram-positive cocci. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Selected compounds (1-13) were examined for cytotoxicity, antitumor, and anti-HIV activity. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  20. Isoxazole-type derivatives related to combretastatin A-4, synthesis and biological evaluation.

    Science.gov (United States)

    Kaffy, Julia; Pontikis, Renée; Carrez, Danièle; Croisy, Alain; Monneret, Claude; Florent, Jean-Claude

    2006-06-15

    Novel combretastatin analogues bearing various five-membered heterocycles with consecutive oxygen and nitrogen atoms, in place of the olefinic bridge of CA4, have been synthesized (isoxazole, isoxazoline, oxadiazole, etc). These compounds have been evaluated for cytotoxicity and their ability to inhibit the tubulin assembly. On the basis of the relative position of the aromatic A- and B-rings on the heterocyclic moiety, they could be split in two classes, the alpha,gamma- or alpha,beta-diaryl heterocyclic derivatives. In the first series, the 3,5-diaryloxadiazole 9a displayed comparable antitubulin activity to that of CA4, but was devoid of cytotoxic effects. Among the alpha,beta-diaryl heterocyclic derivatives, the 4,5-diarylisoxazole 35 exhibited greater antitubulin activity than that of CA4 (0.75 vs 1.2 microM), but modest antiproliferative activity. These data showed that minor alteration in the chemical structure of the heterocyclic ring and its relative orientation with regard to the two phenyl rings of CA4 could dramatically influence the tubulin binding properties.

  1. Pyridine-substituted thiazolylphenol derivatives: Synthesis, modeling studies, aromatase inhibition, and antiproliferative activity evaluation.

    Science.gov (United States)

    Ertas, Merve; Sahin, Zafer; Berk, Barkin; Yurttas, Leyla; Biltekin, Sevde N; Demirayak, Seref

    2018-04-01

    Drugs used in breast cancer treatments target the suppression of estrogen biosynthesis. During this suppression, the main goal is to inhibit the aromatase enzyme that is responsible for the cyclization and structuring of estrogens either with steroid or non-steroidal-type inhibitors. Non-steroidal derivatives generally have a planar aromatic structure attached to the triazole ring system in their structures, which inhibits hydroxylation reactions during aromatization by coordinating the heme group. Bioisosteric replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase the selectivity for aromatase enzyme inhibition. In this study, pyridine-substituted thiazolylphenol derivatives, which are non-steroidal triazole bioisosteres, were synthesized using the Hantzsch method, and physical analysis and structural determination studies were performed. The IC 50 values of the compounds were determined by a fluorescence-based aromatase inhibition assay. Then, their antiproliferative activities on the MCF7 and HEK 293 cell lines were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, the crystal structure of human placental aromatase was subjected to a series of docking experiments to identify the possible interactions between the most active structure and the active site. Lastly, an in silico technique was performed to analyze and predict the drug-likeness, molecular and ADME properties of the synthesized molecules. © 2018 Deutsche Pharmazeutische Gesellschaft.

  2. Cytotoxicity evaluation of polymer-derived ceramics for pacemaker electrode applications.

    Science.gov (United States)

    Grossenbacher, Jonas; Gullo, Maurizio R; Dalcanale, Federico; Blugan, Gurdial; Kuebler, Jakob; Lecaudé, Stéphanie; Tevaearai Stahel, Hendrik; Brugger, Juergen

    2015-11-01

    Ceramics are known to be chemically stable, and the possibility to electrically dope polymer-derived ceramics makes it a material of interest for implantable electrode applications. We investigated cytotoxic characteristics of four polymer-derived ceramic candidates with either electrically conductive or insulating properties. Cytotoxicity was assessed by culturing C2C12 myoblast cells under two conditions: by exposing them to material extracts and by putting them directly in contact with material samples. Cell spreading was optically evaluated by comparing microscope observations immediately after the materials insertion and after 24 h culturing. Cell viability (MTT) and mortality (LDH) were quantified after 24-h incubation in contact with the materials. Comparison was made with biocompatible positive references (alumina, platinum, biocompatible stainless steel 1.4435), negative references (latex, stainless steel 1.4301) and controls (no material present in the culture wells). We found that the cytotoxic properties of tested ceramics are comparable to established reference materials. These ceramics, which are reported to be very stable, can be microstructured and electrically doped to a wide range of conductivity and are thus excellent candidates for implantable electrode applications including pacemakers. © 2015 Wiley Periodicals, Inc.

  3. Evaluation of the Effects of Novel Nafimidone Derivatives on Thermal Hypoalgesia in Mice with Diabetic Neuropathy

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    Suat Kamışlı

    2013-03-01

    Full Text Available Objective: Diabetic neuropathy (DN is a common complication in Diabetes Mellitus. The streptozotocin-induced diabetic rodent is the most commonly used animal model of diabetes and increased sodium channel expression and activity were revealed in this model. At this study, we evaluated the effect of three different nafimidone derivatives which have possible anticonvulsant activity on disorders of thermal pain sensation in diabetic mice. Study Design: Randomized animal experiment. Material and Methods: Mice were divided randomly into five groups (5 mice per group: Control, Diabetes, Dibetes+C1, Diabetes+C2, Diabetes+C3. We used hot and cold plate, and tail-immersion tests for assessment of thermal nociceptive responses. Results: Compared with the control group, the hot-plate response time and the number of paw liftings on cold plate as important indicators of loss of sensation increased, but no significant difference (p>0.05 was found in tail-immersion response time test in diabetes group. C3 compound moved it back to control group levels in the all of three tests. C1 and C2 compounds were effective only in cold-plate test. Conclusion: Nafimidone derivatives may be effective in the cases where epilepsy and diabetes occur together since it has shown efficacy against “loss of sensation” which evolves in diabetic neuropathy over time as well as its antiepileptic effect.

  4. Evaluating effects of L-carnitine on human bone-marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Fujisawa, Koichi; Takami, Taro; Fukui, Yumi; Quintanilha, Luiz Fernando; Matsumoto, Toshihiko; Yamamoto, Naoki; Sakaida, Isao

    2017-05-01

    Mesenchymal stem cells (MSCs) are multipotent cells showing potential for use in regenerative medicine. Culture techniques that are more stable and methods for the more efficient production of MSCs with therapeutic efficacy are needed. We evaluate the effects of growing bone marrow (Bm)-derived MSCs in the presence of L-carnitine, which is believed to promote lipid metabolism and to suppress apoptosis. The presence of L-carnitine decreased the degree of drug-induced apoptosis and suppressed adipogenic differentiation. Metabolomic analysis by means of the exhaustive investigation of metabolic products showed that, in addition to increased β-oxidation and the expression of all carnitine derivatives other than deoxycarnitine (an intermediate in carnitine synthesis), polysaturated and polyunsaturated acids were down-regulated. An integrated analysis incorporating both serial analysis of gene expression and metabolomics revealed increases in cell survival, suggesting the utility of carnitine. The addition of carnitine elevated the oxygen consumption rate by BmMSCs that had been cultured for only a few generations and those that had become senescent following repeated replication indicating that mitochondrial activation occurred. Our exhaustive analysis of the effects of various carnitine metabolites thus suggests that the addition of L-carnitine to BmMSCs during expansion enables efficient cell production.

  5. Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Senchuan Song

    2013-12-01

    Full Text Available Attempting to improve the anticancer activity and solubility of evodiamine in simulated gastric fluid (SGF and simulated intestinal fluid (SIF solutions, thirty-eight N13-substituted evodiamine derivatives were designed, synthesized and tested for antitumor activities against six kinds of human cancer cell lines, namely prostate cancer (DU-145 and PC-3, lung cancer (H460, breast cancer (MCF-7, colon cancer (HCT-5 and glioblastoma (SF-268. The solubility of these compounds in SGF and SIF solutions was evaluated, and apoptosis induced by 2-2, 2-3, 2-16 and 3-2 was determined. The results showed: (1 among all compounds examined, 2-16 showed the highest antitumor activity and a broader spectrum of activity, with IC50 values ranging from 1–2 µM; (2 their solubility was obviously improved; (3 2-3, 2-16 and 3-2 had a significant impact inducing apoptosis in some cancer cell lines. The preliminary structure-activity relationships of these derivatives were discussed.

  6. Synthesis and biological evaluation of novel 5-hydroxylaminoisoxazole derivatives as lipoxygenase inhibitors and metabolism enhancing agents.

    Science.gov (United States)

    Averina, Elena B; Vasilenko, Dmitry A; Gracheva, Yulia A; Grishin, Yuri K; Radchenko, Eugene V; Burmistrov, Vladimir V; Butov, Gennady M; Neganova, Margarita E; Serkova, Tatyana P; Redkozubova, Olga M; Shevtsova, Elena F; Milaeva, Elena R; Kuznetsova, Tamara S; Zefirov, Nikolay S

    2016-02-15

    A versatile synthesis of novel 5-hydroxylaminoisoxazoles bearing adamantane moieties has been accomplished using the heterocyclization reactions of readily available unsaturated esters by the treatment with tetranitromethane in the presence of triethylamine and subsequent reduction of resulting 5-nitroisoxazoles by SnCl2 with the participation of THF. A number of obtained isoxazole derivatives were evaluated for their antioxidative activity, inhibition of lipoxygenases and impact on the rat liver mitochondria. The majority of tested compounds demonstrated moderate antiradical activity in DPPH test (up to EC50 16μM). The same compounds strongly inhibited soybean lipoxygenase (up to IC50 0.4μM) and Fe(2+)- and Fe(3+)-induced lipid peroxidation (LP) of rat brain cortex homogenate (up to IC50 0.3μM). All tested isoxazole derivatives promoted the phosphorylating respiratory activity simultaneously with maximal stimulated respiratory activity of mitochondria and do not reveal any toxicity towards the primary culture of rat cortex neurons. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Evaluation of the performance of hydrological variables derived from GLDAS-2 and MERRA-2 in Mexico

    Science.gov (United States)

    Real-Rangel, R. A.; Pedrozo-Acuña, A.; Breña-Naranjo, J. A.

    2017-12-01

    Hydrological studies have found in data assimilation systems and global reanalysis of land surface variables (e.g soil moisture, streamflow) a wide range of applications, from drought monitoring to water balance and hydro-climatology variability assessment. Indeed, these hydrological data sources have led to an improvement in developing and testing monitoring and prediction systems in poorly gauged regions of the world. This work tests the accuracy and error of land surface variables (precipitation, soil moisture, runoff and temperature) derived from the data assimilation reanalysis products GLDAS-2 and MERRA-2. Validate the performance of these data platforms must be thoroughly evaluated in order to consider the error of hydrological variables (i.e., precipitation, soil moisture, runoff and temperature) derived from the reanalysis products. For such purpose, a quantitative assessment was performed at 2,892 climatological stations, 42 stream gauges and 44 soil moisture probes located in Mexico and across different climate regimes (hyper-arid to tropical humid). Results show comparisons between these gridded products against ground-based observational stations for 1979-2014. The results of this analysis display a spatial distribution of errors and accuracy over Mexico discussing differences between climates, enabling the informed use of these products.

  8. Evaluating Chagas disease progression and cure through blood-derived biomarkers: a systematic review.

    Science.gov (United States)

    Requena-Méndez, Ana; López, Manuel Carlos; Angheben, Andrea; Izquierdo, Luis; Ribeiro, Isabela; Pinazo, Maria-Jesús; Gascon, Joaquim; Muñoz, José

    2013-09-01

    This article reviews the usefulness of various types of blood-derived biomarkers that are currently being studied to predict the progression of Chagas disease in patients with the indeterminate form, to assess the efficacy of antiparasitic drugs and to identify early cardiac and gastrointestinal damage. The authors used a search strategy based on MEDLINE, Cochrane Library Register for systematic review, EmBase, Global Health and LILACS databases. Out of 1716 screened articles, only 166 articles were eligible for final inclusion. The authors classified the biomarkers according to their biochemical structure and primary biological activity in four groups: i) markers of inflammation and cellular injury, ii) metabolic biomakers, iii) prothrombotic biomarkers and iv) markers derived from specific antigens of the parasite. Several potential biomarkers might have clinical potential for the detection of early cardiopathy. Such capacity is imperative in order to detect high-risk patients who require intensive monitoring and earlier therapy. Prospective studies with longer follow-ups are needed for the appraisal of biomarkers assessing clinical or microbiological cure after therapy. At the same time, studies evaluating more than one biomarker are useful to compare the efficacy among them given the lack of a recognized gold standard.

  9. Evaluation of atmospheric particulate concentrations derived from analysis of ratio Thematic Mapper data

    Science.gov (United States)

    Carnahan, W. H.; Mausel, P. W.; Zhou, G. P.

    1984-01-01

    An approach for atmospheric particulate concentration evaluation above urban areas using ratio Thematic Mapper (TM) data is discussed. October 25, 1982 TM data over Chicago, IL are analyzed using TM band ratios of 1/2, 1/3, 1/4, 1/5, and 1/6 and particulate concentration estimates derived from TM ratios are tested over low reflective turbid water sites and highly reflective concrete highways. From analysis of the data it is evident that for water, the pattern of increasing particulate concentration is associated with decreasing ratio values in all band combinations used. Over concrete features, the TM band 1/4 ratio values follow the predicted pattern, while the TM band 1/6 has ratios which are reversed from anticipated values.

  10. Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives.

    Science.gov (United States)

    França, Paulo H B; Da Silva-Júnior, Edeildo F; Aquino, Pedro G V; Santana, Antônio E G; Ferro, Jamylle N S; De Oliveira Barreto, Emiliano; Do Ó Pessoa, Cláudia; Meira, Assuero Silva; De Aquino, Thiago M; Alexandre-Moreira, Magna S; Schmitt, Martine; De Araújo-Júnior, João X

    2016-03-01

    Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L(-1) against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

  11. Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives

    Directory of Open Access Journals (Sweden)

    França Paulo H. B.

    2016-03-01

    Full Text Available Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma, MDA-MB-435 (melanoma and SF-295 (glioblastoma were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L−1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

  12. Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors

    Directory of Open Access Journals (Sweden)

    Lushan Yu

    2013-03-01

    Full Text Available Three series of 3-(2-aminoheterocycle-4-benzyloxyphenylbenzamide derivatives, 2-aminooxazoles, 2-aminothiazoles, and 2-amino-6H-1,3,4-thiadizines were designed, synthesized and evaluated as β-secretase (BACE-1 inhibitors. Preliminary structure-activity relationships revealed that the existence of a 2-amino-6H-1,3,4-thiadizine moiety and α-naphthyl group were favorable for BACE-1 inhibition. Among the synthesized compounds, 5e exhibited the most potent BACE-1 inhibitory activity, with an IC50 value of 9.9 μΜ and it exhibited high brain uptake potential in Madin-Darby anine kidney cell lines (MDCK and a Madin-Darby canine kidney-multidrug resistance 1 (MDCK-MDR1 model.

  13. Design, synthesis and evaluation of 3-(2-aminoheterocycle)-4-benzyloxyphenylbenzamide derivatives as BACE-1 inhibitors.

    Science.gov (United States)

    Shangguan, Shihao; Wang, Fei; Liao, Yong; Yu, Haiping; Li, Jia; Huang, Wenhai; Hu, Haihong; Yu, Lushan; Hu, Yongzhou; Sheng, Rong

    2013-03-20

    Three series of 3-(2-aminoheterocycle)-4-benzyloxyphenylbenzamide derivatives, 2-aminooxazoles, 2-aminothiazoles, and 2-amino-6H-1,3,4-thiadizines were designed, synthesized and evaluated as β-secretase (BACE-1) inhibitors. Preliminary structure-activity relationships revealed that the existence of a 2-amino-6H-1,3,4-thiadizine moiety and α-naphthyl group were favorable for BACE-1 inhibition. Among the synthesized compounds, 5e exhibited the most potent BACE-1 inhibitory activity, with an IC50 value of 9.9 μΜ and it exhibited high brain uptake potential in Madin-Darby anine kidney cell lines (MDCK) and a Madin-Darby canine kidney-multidrug resistance 1 (MDCK-MDR1) model.

  14. Synthesis and Antibacterial Evaluation of New N-acylhydrazone Derivatives from Dehydroabietic Acid

    Directory of Open Access Journals (Sweden)

    Chenhai Gu

    2012-04-01

    Full Text Available A series of new N-acylhydrazone derivatives were synthesized in good yields through the reactions of dehydroabietic acid hydrazide with a variety of substituted arylaldehydes. The structures of the synthesized compounds were confirmed by IR, 1H- and 13C-NMR, ESI-MS, elemental analysis and single crystal X-ray diffraction. From the crystal structure of compound 4l, the C=N double bonds of these N-acylhydrazones showed (E-configuration, while the NMR data of compounds 4a–q indicated the existence of two rotamers for each compound in solution. The target compounds were evaluated for their antibacterial activities against four microbial strains. The result suggested that several compounds exhibited pronounced antibacterial activities. Particularly, compound 4p exhibited good antibacterial activity against Staphylococcus aureus and Bacillus subtilis comparable to positive control. The possible antibacterial metabolism and the strategy for further optimization of this compound were also discussed.

  15. Design, synthesis and evaluation of aromatic heterocyclic derivatives as potent antifungal agents.

    Science.gov (United States)

    Zhao, Shizhen; Zhang, Xiangqian; Wei, Peng; Su, Xin; Zhao, Liyu; Wu, Mengya; Hao, Chenzhou; Liu, Chunchi; Zhao, Dongmei; Cheng, Maosheng

    2017-09-08

    To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (1), a series of aromatic heterocyclic derivatives were designed, synthesized and evaluated for in vitro antifungal activity. Many of the target compounds showed good inhibitory activity against Candida albicans and Cryptococcus neoformans. In particular, the isoxazole nuclei were more suited for improving the activity against Aspergillus spp. Among these compounds, 2-F substituted analogues 23g and 23h displayed the most remarkable in vitro activity against Candida spp., C. neoformans, A. fumigatus and fluconazole-resistant C.alb. strains, which is superior or comparable to the activity of the reference drugs fluconazole and voriconazole. Notably, the compounds 23g and 23h exhibited low inhibition profiles for various isoforms of human cytochrome P450 and excellent blood plasma stability. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Design, Synthesis and Antifungal/Insecticidal Evaluation of Novel Cinnamide Derivatives

    Directory of Open Access Journals (Sweden)

    Yanjun Xu

    2011-10-01

    Full Text Available Twenty novel cinnamamide derivatives were designed and synthesized using as lead compound pyrimorph, whose morpholine moiety was replaced by β-phenylethylamine. All the compounds were characterized by their spectroscopic data. The fungicidal and insecticidal activities were also evaluated. The preliminary results showed that all the title compounds had certain fungicidal activities against seven plant pathogens at a concentration of 50 μg/mL, and compounds 11a and 11l showed inhibition ratios of up to 90% against R. solani. Most of the title compounds exhibited moderate nematicidal activities. In general, the morpholine ring may be replaced by other amines and a chlorine atom in the pyridine ring is helpful to fungicidal activity.

  17. Derivation and evaluation of land surface temperature from the geostationary operational environmental satellite series

    Science.gov (United States)

    Fang, Li

    The Geostationary Operational Environmental Satellites (GOES) have been continuously monitoring the earth surface since 1970, providing valuable and intensive data from a very broad range of wavelengths, day and night. The National Oceanic and Atmospheric Administration's (NOAA's) National Environmental Satellite, Data, and Information Service (NESDIS) is currently operating GOES-15 and GOES-13. The design of the GOES series is now heading to the 4 th generation. GOES-R, as a representative of the new generation of the GOES series, is scheduled to be launched in 2015 with higher spatial and temporal resolution images and full-time soundings. These frequent observations provided by GOES Image make them attractive for deriving information on the diurnal land surface temperature (LST) cycle and diurnal temperature range (DTR). These parameters are of great value for research on the Earth's diurnal variability and climate change. Accurate derivation of satellite-based LSTs from thermal infrared data has long been an interesting and challenging research area. To better support the research on climate change, the generation of consistent GOES LST products for both GOES-East and GOES-West from operational dataset as well as historical archive is in great demand. The derivation of GOES LST products and the evaluation of proposed retrieval methods are two major objectives of this study. Literature relevant to satellite-based LST retrieval techniques was reviewed. Specifically, the evolution of two LST algorithm families and LST retrieval methods for geostationary satellites were summarized in this dissertation. Literature relevant to the evaluation of satellite-based LSTs was also reviewed. All the existing methods are a valuable reference to develop the GOES LST product. The primary objective of this dissertation is the development of models for deriving consistent GOES LSTs with high spatial and high temporal coverage. Proper LST retrieval algorithms were studied

  18. Synthesis and evaluation of two novel 2-nitroimidazole derivatives as potential PET radioligands for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zha Zhihao; Zhu Lin [Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875 (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19014 (United States); Liu Yajing; Du Fenghua; Gan Hongmei; Qiao Jinping [Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875 (China); Kung, Hank F., E-mail: kunghf@gmail.co [Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875 (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19014 (United States)

    2011-05-15

    Introduction: Nitroimidazole (azomycin) derivatives labeled with radioisotopes have been developed as cancer imaging and radiotherapeutic agents based on the oncological hypoxic mechanism. By attaching nitroimidazole core with different functional groups, we synthesized new nitroimidazole derivatives and evaluated their potentiality as tumor imaging agents. Methods: Starting with commercially available 2-nitroimidazole, 2-fluoro-N-(2-(2-nitro-1H-imidazol-1-yl)ethyl)acetamide (NEFA, [{sup 19}F]7) and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 2-fluoroacetate (NEFT, [{sup 19}F]8), as well as radiolabeling precursors, the bromo-substituted analogs were quickly synthesized through a three-step synthetic pathway. The precursors were radiolabeled with [{sup 18}F]F{sup -}/18-crown-6/KHCO{sub 3} in dimethyl sulfoxide at 90{sup o}C for 10 min followed by purification with an Oasis HLB cartridge. Biodistribution studies were carried out in EMT-6 tumor-bearing mice. The uptake (%ID/g) in tumors and normal tissues were measured at 30 min postinjection. Liquid chromatography-electrospray ionization mass spectrometry (LC/MS) was used to distinguish metabolites from parent drugs in urine and plasma of rat injected with 'cold' NEFA ([{sup 19}F]7) and NEFT ([{sup 19}F]8). Results: Two radiotracers, [{sup 18}F]NEFA ([{sup 18}F]7) and [{sup 18}F]NEFT ([{sup 18}F]8), were prepared with average yields of 6%-7% and 9%-10% (not decay corrected). Radiochemical purity for both tracers was >95% as determined by HPLC. Biodistribution studies in EMT-6 tumor-bearing mice indicated that the tumor to blood and tumor to liver ratios of both [{sup 18}F]7 (0.96, 0.61) and [{sup 18}F]8 (0.98, 1.10) at 30 min were higher than those observed for [{sup 18}F]FMISO (1) (0.91, 0.59), a well-investigated azomycin-type hypoxia radiotracer. Liquid chromatography-electrospray ionization mass spectrometry analysis demonstrated that fluoroacetate was the main in vivo metabolite for both NEFA ([{sup 19

  19. Evaluation of potential interactions between mycophenolic acid derivatives and proton pump inhibitors.

    Science.gov (United States)

    Gabardi, Steven; Olyaei, Ali

    2012-01-01

    To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs). An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed. Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions. GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction. A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity

  20. Synthesis and phytotoxic activity of 1,2,3-triazole derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Borgati, Thiago F.; Alves, Rosemeire B., E-mail: thfborgati@gmail.com, E-mail: rosebrondi@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Quimica; Teixeira, Robson R.; Freitas, Rossimiriam P. de; Perdigao, Thays G.; Silva, Silma F. da; Santos, Aline Aparecida dos [Universidade Federal de Vicosa, MG (Brazil). Departamento de Quimica; Bastidas, Alberto de Jesus O. [Laboratorio de Quimica Ecologica, Departamento de Quimica, Universidad de Los Andes, Nucleo Universitario Pedro Rincon Gutierrez, Merida (Viet Nam)

    2013-06-15

    Thirteen triazole derivatives bearing halogenated benzyl substituents were synthesized using the Cu-catalyzed azide-alkyne cycloaddition (CuAAC), a leading example of the click chemistry approach, as the key step. The biological activity of the compounds was evaluated, and it was found that these compounds interfere with the germination and radicle growth (shoots and roots) of two dicotyledonous species, Lactuca sativa and Cucumis sativus, and one monocotyledonous species, Allium cepa. The compounds showed predominantly inhibitory activity related to the evaluated species mainly at the concentration of 10{sup -4} mol L{sup -1}. Some of them presented inhibitory activity comparable to 2,4-D (2,4-dichlorophenoxyacetic acid), used as positive control. (author)

  1. Synthesis and phytotoxic activity of 1,2,3-triazole derivatives

    International Nuclear Information System (INIS)

    Borgati, Thiago F.; Alves, Rosemeire B.

    2013-01-01

    Thirteen triazole derivatives bearing halogenated benzyl substituents were synthesized using the Cu-catalyzed azide-alkyne cycloaddition (CuAAC), a leading example of the click chemistry approach, as the key step. The biological activity of the compounds was evaluated, and it was found that these compounds interfere with the germination and radicle growth (shoots and roots) of two dicotyledonous species, Lactuca sativa and Cucumis sativus, and one monocotyledonous species, Allium cepa. The compounds showed predominantly inhibitory activity related to the evaluated species mainly at the concentration of 10 -4 mol L -1 . Some of them presented inhibitory activity comparable to 2,4-D (2,4-dichlorophenoxyacetic acid), used as positive control. (author)

  2. Evaluation of 1,3-benzoxathiol-2-one Derivatives as Potential Antifungal Agents.

    Science.gov (United States)

    Terra, Luciana; de L Chazin, Eliza; de S Sanches, Paola; Saito, Max; de Souza, Marcus V N; Gomes, Claudia R B; Wardell, James L; Wardell, Solange M S V; Sathler, Plinio C; Silva, Gabriela C C; Lione, Viviane O; Kalil, Marcos; Joffily, Ana; Castro, Helena C; Vasconcelos, Thatyana R A

    2018-01-01

    Over the last few years, fungal infections have emerged as a worrisome global public health problem. Candidiasis is a disease caused by Candida species and has been a problem worldwide mainly for immunosuppressed patients. Lately, the resistant strains and side effects have been reported as important issues for treating Candidiasis, which have to be solved by identifying new drugs. The goal of this work was to synthesize a series of 1,3-benzoxathiol-2-one derivatives, XYbenzo[ d][1,3]oxathiol-2-ones, and evaluate their antifungal activity against five Candida species. In vitro antifungal screening test and minimum inhibitory concentration determination were performed according to CLSI protocols using ketoconazole as the reference drug. The cytotoxicity of the most active compounds was evaluated by hemolysis and MTT (Vero cells) assays. Compounds 2 (XY = 6-hydroxy-5-nitro, MIC = 4-32 µg/mL) and 7 (XY = 6-acetoxy-5-nitro, MIC =16-64 µg/mL) showed good results when compared with current antifungals in CLSI values (MIC = 0.04-250 µg/mL). These compounds exhibited a safer cytotoxicity as well as a lower hemolytic profile than ketoconazole. Overall, the in vitro results pointed to the potential of compounds 2 and 7 as new antifungal prototypes to be further explored. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Design, synthesis and biological evaluation of novel hydrogen sulfide releasing capsaicin derivatives.

    Science.gov (United States)

    Gao, Mingxiang; Li, Jinyu; Nie, Cunbin; Song, Beibei; Yan, Lin; Qian, Hai

    2018-05-15

    Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active component in chili peppers with health-promoting benefits. However, its use is limited by the low bioavailability and irritating quality. In this study, for improving the activity of CAP and alleviating its irritating effects, a series of H 2 S-releasing CAPs were designed and synthesized by combining capsaicin and dihydro capsaicin with various hydrogen sulfide donors. The resulting compounds were evaluated their TRPV1 agonist activity, analgesic activity, anticancer activities, H 2 S-releasing ability, and gastric mucosa irritation. Biological evaluation indicated that the most active compound B 9 , containing 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H 2 S donor, had better analgesic activity and displayed more potent cytotoxic effects on the test cell lines than the lead compound CAP. Furthermore, the preferred compound, B 9 reduced rat gastric mucosa irritation caused by CAP. Notably, the improved properties of this derivative are associated with its H 2 S-releasing capability. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Synthesis and Biological Evaluation of Novel 2-Methoxypyridylamino-Substituted Riminophenazine Derivatives as Antituberculosis Agents

    Directory of Open Access Journals (Sweden)

    Dongfeng Zhang

    2014-04-01

    Full Text Available Clofazimine, a member of the riminophenazine class, is one of the few antibiotics that are still active against multidrug-resistant Mycobacterium tuberculosis (M. tuberculosis. However, the clinical utility of this agent is limited by its undesirable physicochemical properties and skin pigmentation potential. With the goal of maintaining potent antituberculosis activity while improving physicochemical properties and lowering skin pigmentation potential, a series of novel riminophenazine derivatives containing a 2-methoxypyridylamino substituent at the C-2 position of the phenazine nucleus were designed and synthesized. These compounds were evaluated for antituberculosis activity against M. tuberculosis H37Rv and screened for cytotoxicity. Riminophenazines bearing a 3-halogen- or 3,4-dihalogen-substituted phenyl group at the N-5 position exhibited potent antituberculosis activity, with MICs ranging from 0.25~0.01 μg/mL. The 3,4-dihalogen- substituted compounds displayed low cytotoxicity, with IC50 values greater than 64 μg/mL. Among these riminophenazines, compound 15 exhibited equivalent in vivo efficacy against M. tuberculosis infection and reduced skin discoloration potential in an experimental mouse infection model as compared to clofazimine. Compound 15, as compared to clofazimine, also demonstrated improved physicochemical properties and pharmacokinetic profiles with a short half-life and less drug tissue accumulation. This compound is being evaluated as a potential drug candidate for the treatment of multidrug resistant tuberculosis.

  5. Comparative evaluation of thermal degradation for biodiesels derived from various feedstocks through transesterification

    International Nuclear Information System (INIS)

    Li, Hui; Niu, Sheng-li; Lu, Chun-mei; Cheng, Shi-qing

    2015-01-01

    Highlights: • TG–FTIR is employed to evaluate thermal degradation characteristics of biodiesels. • Lower content of unsaturated fatty acid is responsible for higher thermal stability. • Evolved products are alkanes, aldehyde/ketones, ethers, alkenes and CO 2 . - Abstract: Biodiesel is commonly derived from various feedstocks through transesterification. Since thermal degradation is concerned with a lot of scientific applications, it is essential to evaluate the thermal degradation characteristics for biodiesel. In this study, thermal degradation of biodiesel is investigated through thermogravimetric analysis (TGA) coupled with Fourier transform infrared spectroscopy (FTIR). The fatty acid composition and the characteristic functional groups of biodiesel are detected by gas chromatography (GC) and FTIR in advance. Then, TGA experiments are conducted at linear heating rates from 20 °C min −1 to 40 °C min −1 under nitrogen atmosphere in temperature range from 25 °C to 600 °C. Subsequently, the activation energy, including enthalpy, is determined by Friedman method and Flynn–Wall–Ozawa method and the reaction order is calculated through the Avrami theory. In addition, the pre-exponential factor, the Gibbs free energy, and the entropy are also calculated. Finally, to obtain a comprehensive understanding for thermal degradation of biodiesels, all evolved products are detected by FTIR in real time

  6. Evaluation of mental stress by physiological indices derived from finger plethysmography.

    Science.gov (United States)

    Minakuchi, Emiko; Ohnishi, Eriko; Ohnishi, Junji; Sakamoto, Shigeko; Hori, Miyo; Motomura, Miwa; Hoshino, Junichi; Murakami, Kazuo; Kawaguchi, Takayasu

    2013-10-12

    Quantitative evaluation of mental stress is important to prevent stress-related disorders. Finger plethysmography (FPG) is a simple noninvasive method to monitor peripheral circulation, and provides many physiological indices. Our purpose is to investigate how FPG-derived indices reflect on mental stress, and to clarify any association between these physiological indices and subjective indices of mental stress. Thirty-one healthy women (mean age, 22 years ± 2) participated. The participants rested by sitting on a chair for 10 min. They then performed a computerized version of the Stroop color-word conflict test (CWT) for 10 min. Finally, they rested for 10 min. FPG was recorded throughout the experiment. The participants completed a brief form of the Profile of Mood States (POMS) questionnaire before and after the test. Using the FPG data, we conducted chaos analysis and fast Fourier transform analysis, and calculated chaotic attractors, the largest Lyapunov exponent, a high-frequency (HF) component, a low-to-high-frequency (LF/HF) ratio, finger pulse rate and finger pulse wave amplitude. The HF component decreased and the LF/HF ratio increased significantly during the test (P stress. Our findings indicate that FPG is one of the easiest methods to evaluate mental stress quantitatively. In particular, the largest Lyapunov exponent and the LF/HF ratio might be associated with acute mental stress. Farther examination is needed to find any association between the physiological indices and various types of mental stress.

  7. Evaluation of self-combustion risk in tire derived aggregate fills.

    Science.gov (United States)

    Arroyo, Marcos; San Martin, Ignacio; Olivella, Sebastian; Saaltink, Maarten W

    2011-01-01

    Lightweight tire derived aggregate (TDA) fills are a proven recycling outlet for waste tires, requiring relatively low cost waste processing and being competitively priced against other lightweight fill alternatives. However its value has been marred as several TDA fills have self-combusted during the early applications of this technique. An empirical review of these cases led to prescriptive guidelines from the ASTM aimed at avoiding this problem. This approach has been successful in avoiding further incidents of self-combustion. However, at present there remains no rational method available to quantify self-combustion risk in TDA fills. This means that it is not clear which aspects of the ASTM guidelines are essential and which are accessory. This hinders the practical use of TDA fills despite their inherent advantages as lightweight fill. Here a quantitative approach to self-combustion risk evaluation is developed and illustrated with a parametric analysis of an embankment case. This is later particularized to model a reported field self-combustion case. The approach is based on the available experimental observations and incorporates well-tested methodological (ISO corrosion evaluation) and theoretical tools (finite element analysis of coupled heat and mass flow). The results obtained offer clear insights into the critical aspects of the problem, allowing already some meaningful recommendations for guideline revision. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Deriving evaluation indicators for knowledge transfer and dialogue processes in the context of climate research

    Science.gov (United States)

    Treffeisen, Renate; Grosfeld, Klaus; Kuhlmann, Franziska

    2017-12-01

    Knowledge transfer and dialogue processes in the field of climate science have captured intensive attention in recent years as being an important part of research activities. Therefore, the demand and pressure to develop a set of indicators for the evaluation of different activities in this field have increased, too. Research institutes are being asked more and more to build up structures in order to map these activities and, thus, are obliged to demonstrate the success of these efforts. This paper aims to serve as an input to stimulate further reflection on the field of evaluation of knowledge transfer and dialogue processes in the context of climate sciences. The work performed in this paper is embedded in the efforts of the German Helmholtz Association in the research field of earth and environment and is driven by the need to apply suitable indicators for knowledge transfer and dialogue processes in climate research center evaluations. We carry out a comparative analysis of three long-term activities and derive a set of indicators for measuring their output and outcome by balancing the wide diversity and range of activity contents as well as the different tools to realize them. The case examples are based on activities which are part of the regional Helmholtz Climate Initiative Regional Climate Change (REKLIM) and the Climate Office for Polar Regions and Sea Level Rise at the Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research. Both institutional units have been working on a wide range of different knowledge transfer and dialogue processes since 2008/2009. We demonstrate that indicators for the evaluation must be based on the unique objectives of the individual activities and the framework they are embedded in (e.g., research foci which provide the background for the performed knowledge transfer and dialogue processes) but can partly be classified in a principle two-dimensional scheme. This scheme might serve as a usable basis for climate

  9. Forecasting and evaluations of crude oil processing and oil derivatives consumption in Republic of Macedonia up to 2000 year

    International Nuclear Information System (INIS)

    Janevski, Risto

    1998-01-01

    Elaboration of various analysis in an energetic field is a quite usual, but inevitable action, procedure and investigation. Also, in a field of crude oil processing and oil derivatives consumption these analyses are a base for making a various range of forecasting and evaluations. How many of these forecasting and evaluations will be credible it depends mostly of diligent, precise and accurate data and experiences in the previous years. This part refers to forecasting and evaluations of crude oil processing and oil derivatives consumption in a short period up to 2000 year in Republic of Macedonia. (Author)

  10. Asymmetric synthesis of all-carbon benzylic quaternary stereocenters via Cu-catalyzed conjugate addition of dialkylzinc reagents to 5-(1-arylalkylidene) Meldrum's acids.

    Science.gov (United States)

    Fillion, Eric; Wilsily, Ashraf

    2006-03-08

    The asymmetric synthesis of all-carbon benzylic quaternary stereocenters has been successfully achieved through copper-catalyzed addition of dialkylzinc reagents to 5-(1-arylalkylidene) and 5-(dihydroindenylidene) Meldrum's acids in the presence of phosphoramidite ligand. The resulting benzyl-substituted Meldrum's acids and 1,1-disubstituted indanes were obtained in good yields and up to 99% ee. The significance of substituting the position para, meta, and ortho to the electrophilic benzylic center was highlighted. A benzyl Meldrum's acid product was further transformed to a 3,3-disubstituted 1-indanone and a beta,beta-disubstituted pentanoic acid.

  11. Synthesis and Biological Evaluation of Novel Jatrorrhizine Derivatives with Amino Groups Linked at the 3-Position as Inhibitors of Acetylcholinesterase

    Directory of Open Access Journals (Sweden)

    Xiaofei Jiang

    2017-01-01

    Full Text Available Jatrorrhizine was considered as one of the active constituents of Coptis chinensis Franch. Herein, jatrorrhizine derivatives with substituted amino groups linked at the 3-position were designed, synthesized, and biologically evaluated as inhibitors of acetylcholinesterase. Jatrorrhizine derivatives inhibited the activity of acetylcholinesterase (AChE to a greater extent than the lead compound jatrorrhizine. All these jatrorrhizine derivatives were proved to be potent inhibitors of acetylcholinesterase (AChE with submicromolar IC50 values, but less sensitive to butyrylcholinesterase (BuChE, which suggests that these jatrorrhizine derivatives are selective for AChE/BuChE. Compound 3g gave the most potent inhibitor activity for AChE (IC50 = 0.301 μM, which is greater than the lead compound jatrorrhizine. All these results demonstrated that these jatrorrhizine derivatives are potential inhibitors for AChE.

  12. Unusual C-C bond cleavage in the formation of amine-bis(phenoxy) group 4 benzyl complexes: Mechanism of formation and application to stereospecific polymerization

    KAUST Repository

    Gowda, Ravikumar R.

    2014-08-11

    Group 4 tetrabenzyl compounds MBn4 (M = Zr, Ti), upon protonolysis with an equimolar amount of the tetradentate amine-tris(phenol) ligand N[(2,4-tBu2C6H2(CH 2)OH]3 in toluene from -30 to 25 °C, unexpectedly lead to amine-bis(phenoxy) dibenzyl complexes, BnCH2N[(2,4- tBu2C6H2(CH2)O] 2MBn2 (M = Zr (1), Ti (2)) in 80% (1) and 75% (2) yields. This reaction involves an apparent cleavage of the >NCH2-ArOH bond (loss of the phenol in the ligand) and formation of the >NCH 2-CH2Bn bond (gain of the benzyl group in the ligand). Structural characterization of 1 by X-ray diffraction analysis confirms that the complex formed is a bis(benzyl) complex of Zr coordinated by a newly derived tridentate amine-bis(phenoxy) ligand arranged in a mer configuration in the solid state. The abstractive activation of 1 and 2 with B(C6F 5)3·THF in CD2Cl2 at room temperature generates the corresponding benzyl cations {BnCH2N[(2,4- tBu2C6H2(CH2)O] 2MBn(THF)}+[BnB(C6F5) 3]- (M = Zr (3), Ti, (4)). These cationic complexes, along with their analogues derived from (imino)phenoxy tri- and dibenzyl complexes, [(2,6-iPr2C6H3)N=C(3,5- tBu2C6H2)O]ZrBn3 (5) and [2,4-Br2C6H2(O)(6-CH2(NC 5H9))CH2N=CH(2-adamantyl-4-MeC 6H2O)]ZrBn2 (6), have been found to effectively polymerize the biomass-derived renewable β-methyl-α-methylene- γ-butyrolactone (βMMBL) at room temperature into the highly stereoregular polymer PβMMBL with an isotacticity up to 99% mm. A combined experimental and DFT study has yielded a mechanistic pathway for the observed unusual C-C bond cleavage in the present protonolysis reaction between ZrBn4 and N[(2,4-tBu2C 6H2(CH2)OH]3 for the formation of complex 1, which involves the benzyl radical and the Zr(III) species, resulting from thermal and photochemical decomposition of ZrBn4, followed by a series of reaction sequences consisting of protonolysis, tautomerization, H-transfer, oxidation, elimination, and radical coupling. © 2014 American Chemical Society.

  13. Catalytic Performance of Co3O4 on Different Activated Carbon Supports in the Benzyl Alcohol Oxidation

    Directory of Open Access Journals (Sweden)

    Misael Cordoba

    2017-12-01

    Full Text Available Co3O4 particles were supported on a series of activated carbons (G60, CNR, RX3, and RB3. Incipient wetness method was used to prepare these catalysts. The effect of the structural and surface properties of the carbonaceous supports during oxidation of benzyl alcohol was evaluated. The synthetized catalysts were characterized via IR, TEM, TGA/MS, XRD, TPR, AAS, XPS, and N2 adsorption/desorption isotherm techniques. Co3O4/G60 and Co3O4/RX3 catalysts have high activity and selectivity on the oxidation reaction reaching conversions above 90% after 6 h, without the presence of promoters. Catalytic performances show that differences in chemistry of support surface play an important role in activity and suggest that the presence of different ratios of species of cobalt and oxygenated groups on surface in Co3O4/G60 and Co3O4/RX3 catalysts, offered a larger effect synergic between both active phase and support increasing their catalytic activity when compared to the other tested catalysts.

  14. n-Butyl benzyl phthalate promotes breast cancer progression by inducing expression of lymphoid enhancer factor 1.

    Directory of Open Access Journals (Sweden)

    Tsung-Hua Hsieh

    Full Text Available Environmental hormones play important roles in regulating the expression of genes involved in cell proliferation, drug resistance, and breast cancer risk; however, their precise role in human breast cancer cells during cancer progression remains unclear. To elucidate the effect of the most widely used industrial phthalate, n-butyl benzyl phthalate (BBP, on cancer progression, we evaluated the results of BBP treatment using a whole human genome cDNA microarray and MetaCore software and selected candidate genes whose expression was changed by more than ten-fold by BBP compared with controls to analyze the signaling pathways in human breast cancer initiating cells (R2d. A total of 473 genes were upregulated, and 468 were downregulated. Most of these genes are involved in proliferation, epithelial-mesenchymal transition, and angiogenesis signaling. BBP induced the viability, invasion and migration, and tube formation in vitro, and Matrigel plug angiogenesis in vivo of R2d and MCF-7. Furthermore, the viability and invasion and migration of these cell lines following BBP treatment was reduced by transfection with a small interfering RNA targeting the mRNA for lymphoid enhancer-binding factor 1; notably, the altered expression of this gene consistently differentiated tumors expressing genes involved in proliferation, epithelial-mesenchymal transition, and angiogenesis. These findings contribute to our understanding of the molecular impact of the environmental hormone BBP and suggest possible strategies for preventing and treating human breast cancer.

  15. Evaluation of antibacterial efficacy of fungal-derived silver nanoparticles against Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    Kiran Rahul Halkai

    2018-01-01

    Full Text Available Background: The main objective of endodontic therapy is complete elimination and prevention of bacteria from the root canal system; however, it is difficult due to anatomical ramifications of root canal system and growing resistant microbes to available disinfectants. Therefore, to overcome this problem, newer antimicrobial agents have to be developed. Aims: The aim of the study was to evaluate the antibacterial efficacy of fungal-derived biosynthesized silver nanoparticles (AgNPs against Enterococcus faecalis. Materials and Methods: Freshly prepared silver nanoparticles using the endophytic fungi Fusarium semitectum, characterized by different techniques were used to evaluate the antibacterial efficacy against E. faecalis by agar well diffusion method measuring the zone of inhibition using different concentrations of nanoparticles (AgNPs (A [20 μl], B [40 μl], C [60 μl], D [80 μl], and E [100 μl], F (0.2% chlorhexidine [CHX], G (2% CHX, H (ampicillin, and I (distilled water were used as control groups. Statistical Analysis Used: One-way ANOVA followed by post hoc Tukey multiple comparison test was done. Results: AgNPs (100 ml showed highest zone of inhibition 19.5 mm against E. faecalis. CHX (0.2% 14.52 mm, CHX (2% 20.02 mm, and ampicillin showed highest mean zone of inhibition 20.5 mm and distilled water showed no zone of inhibition. Results indicate no significant difference between E (100 μl, G (2% CHX, and H (ampicillin (P < 0.0001. Conclusions: Biosynthesized AgNPs exhibit efficient antibacterial activity against E. faecalis and therefore can be used as root canal irrigant or intracanal medicament for root canal disinfection.

  16. Eurotiumins A–E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452

    Directory of Open Access Journals (Sweden)

    Wei-Mao Zhong

    2018-04-01

    Full Text Available Three new prenylated indole 2,5-diketopiperazine alkaloids (1–3 with nine known ones (5–13, one new indole alkaloid (4, and one new bis-benzyl pyrimidine derivative (14 were isolated and characterized from the marine-derived fungus Eurotium sp. SCSIO F452. 1 and 2, occurring as a pair of diastereomers, both presented a hexahydropyrrolo[2,3-b]indole skeleton. Their chemical structures, including absolute configurations, were elucidated by 1D and 2D NMR, HRESIMS, quantum chemical calculations of electronic circular dichroism, and single crystal X-ray diffraction experiments. Most isolated compounds were screened for antioxidative potency. Compounds 3, 5, 6, 7, 9, 10, and 12 showed significant radical scavenging activities against DPPH with IC50 values of 13, 19, 4, 3, 24, 13, and 18 µM, respectively. Five new compounds were evaluated for cytotoxic activities.

  17. Synthesis and Antibacterial Evaluation of New N-acylhydrazone Derivatives from Dehydroabietic Acid

    Directory of Open Access Journals (Sweden)

    Wen Gu

    2012-04-01

    Full Text Available A series of new N-acylhydrazone derivatives were synthesized in good yields through the reactions of dehydroabietic acid hydrazide with a variety of substituted arylaldehydes. The structures of the synthesized compounds were confirmed by IR, 1H- and 13C-NMR, ESI-MS, elemental analysis and single crystal X-ray diffraction. From the crystal structure of compound 4l, the C=N double bonds of these N-acylhydrazones showed (E-configuration, while the NMR data of compounds 4aq indicated the existence of two rotamers for each compound in solution. The target compounds were evaluated for their antibacterial activities against four microbial strains. The result suggested that several compounds exhibited pronounced antibacterial activities. Particularly, compound 4p exhibited good antibacterial activity against Staphylococcus aureus and Bacillus subtilis comparable to positive control. The possible antibacterial metabolism and the strategy for further optimization of this compound were also discussed.

  18. ROS evaluation for a series of CNTs and their derivatives using an ESR method with DMPO

    International Nuclear Information System (INIS)

    Tsuruoka, S; Noguchi, T; Endo, M; Tristan, F; Terrones, M; Takeuchi, K; Koyama, K; Usui, Y; Matsumoto, H; Saito, N; Porter, D W; Castranova, V

    2013-01-01

    Carbon nanotubes (CNTs) are important materials in advanced industries. It is a concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has been recently reported that CNTs scavenge ROS though non-carbon fibers generate ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has not been demonstrated well. The present work specifically investigates ROS scavenging capabilities with a series of CNTs and their derivatives that were physically treated, and with the number of commercially available CNTs. CNT concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not only influenced by physical treatments, but was also dependent on individual manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key parameter to obtain appropriate ROS quenching results for comparison of CNTs. The present results suggest that dangling bonds are not a sole factor for scavenging, and electron transfer on the CNT surface is not clearly determined to be the sole mechanism to explain ROS scavenging.

  19. Mannich-Benzimidazole Derivatives as Antioxidant and Anticholinesterase Inhibitors: Synthesis, Biological Evaluations, and Molecular Docking Study.

    Science.gov (United States)

    Alpan, Ayşe Selcen; Sarıkaya, Görkem; Çoban, Güneş; Parlar, Sülünay; Armagan, Güliz; Alptüzün, Vildan

    2017-07-01

    A series of Mannich bases of benzimidazole derivatives having a phenolic group were designed to assess their anticholinesterase and antioxidant activities. The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities were evaluated in vitro by using Ellman's method. According to the activity results, all of the compounds exhibited moderate to good AChE inhibitory activity (except for 2a), with IC 50 values ranging from 0.93 to 10.85 μM, and generally displayed moderate BuChE inhibitory activity. Also, most of the compounds were selective against BuChE. Compound 4b was the most active molecule on the AChE enzyme and also selective. In addition, we investigated the antioxidant effects of the synthesized compounds against FeCl 2 /ascorbic acid-induced oxidative stress in the rat brain in vitro, and the activity results showed that most of the compounds are effective as radical scavengers. Molecular docking studies and molecular dynamics simulations were also carried out. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Design, Synthesis, and Biological Evaluation of Vanillin Hydroxamic Acid Derivatives as Novel Peptide Deformylase Inhibitors.

    Science.gov (United States)

    Gao, Jian; Qiu, Shengzhi; Liang, Li; Hao, Zhixiang; Zhou, Qianqian; Wang, Fanfan; Mou, Jie; Lin, Qisi

    2018-01-01

    Infectious disease is increasingly hampering human health, which challenge the discovery of new antibacterial target. Peptide deformylase (PDF), a metalloenzyme responsible for catalyzing the removal of the N-formyl group from nascent proteins, was considered as an important target in antibacterial drug discovery. Reported here are the design, synthesis and biological evaluation of vanillin hydroxamic acid derivatives. Analysis of the structure-activity relationships lead to the discovery of compound 8, which exhibits promising antibacterial activity against Escherichia coli, Staphylococcus aureus, Aspergillus oryzae, and Aspergillus foetidus with the MIC value of 0.32 µg/ml, 0.32 µg/ml, 0.16 µg/ml and 0.16 µg/ml, respectively. Furthermore, molecular docking study was applied to elucidate binding interaction between compound 8 and PDF, which indicate that compound 8 not only shares the same binding pocket with actinonin, but also has a similar binding pattern. In silico pharmacokinetic and toxicity prediction studies also suggested that compound 8 has a relatively high drug score of 0.80, and has no risk of toxicity. Compound 8 might represent a promising scaffold for the further development of novel antibacterial drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Immunological evaluation of bacterial derived Cochleate and proteoliposome as mucosal adjuvants.

    Science.gov (United States)

    del Campo, Judith; Lastre, Miriam; Bracho, Gustavo; Rodríguez, Tamara; Gil, Danay; Zayas, Caridad; Taboada, Carlos; Acevedo, Reinaldo; Pérez, Danev Ricardo; Pérez, Oliver

    2006-04-12

    We evaluated the potential of two bacterial derived compounds, Cochleate and Proteoliposome (PL), administrated to mice by nasal or oral routes on induction of antibody and cytokine responses. Anti PL IgG and IgA responses were measured by ELISA in saliva, sera or vaginal fluids of immunized mice. Productions of gammaIFN and IL-5 were determined in spleen cells of immunized mice following a recall in vitro with Cochleate or PL. Intranasal administration elicited a higher anti PL IgA response in both saliva and vaginal fluids as compared with oral route. Mice immunized with Cochleate or PL via intranasal or oral route-induced anti PL IgG and IgG2a antibody responses in their sera and vaginal fluids. Spleen cells from these immunized mice produced gammaIFN, but not IL-5, after a recall in vitro with Cochleate or PL. These results show that Cochleate and PL are capable of inducing both systemic and mucosal antibody responses as well as a Th1 type of immunity as evidenced by high gammaIFN and IgG2a antibody responses.

  2. ROS evaluation for a series of CNTs and their derivatives using an ESR method with DMPO.

    Science.gov (United States)

    Tsuruoka, S; Takeuchi, K; Koyama, K; Noguchi, T; Endo, M; Tristan, F; Terrones, M; Matsumoto, H; Saito, N; Usui, Y; Porter, D W; Castranova, V

    Carbon nanotubes (CNTs) are important materials in advanced industries. It is a concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has been recently reported that CNTs scavenge ROS though non-carbon fibers generate ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has not been demonstrated well. The present work specifically investigates ROS scavenging capabilities with a series of CNTs and their derivatives that were physically treated, and with the number of commercially available CNTs. CNT concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not only influenced by physical treatments, but was also dependent on individual manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key parameter to obtain appropriate ROS quenching results for comparison of CNTs. The present results suggest that dangling bonds are not a sole factor for scavenging, and electron transfer on the CNT surface is not clearly determined to be the sole mechanism to explain ROS scavenging.

  3. Synthesis, Characterization and Antimicrobial Evaluation of some Thiazole-Derived Carbamates, Semicarbazones, Amides and Carboxamide

    International Nuclear Information System (INIS)

    Balawi, N.A.A.; ALShaikh, M.A.A.; Alafeefy, A.M.; Khan, K.M.

    2016-01-01

    This study comprises the synthesis and characterization of twenty thiazole-derived carbamates (3a-e), N-substituted amides (8a-h) and carboxamide (10) from 2-aminothiazoles (1a, b) via nucleophilic substitution reactions with activated carbonyl compounds including, chloroformates (2a-d), acid chlorides (7a-e) and glutaric anhydride (9), respectively. Sequential hydrazinolysis of carbamate (3e) and condensation with a variety of aldehydes and ketones (5a d) afforded the corresponding semicarbazones (6a-d). Some selected synthesized compounds were subjected to in vitro antimicrobial evaluation against common pathogens including, Gram+ve bacteria Bacillus subtilis (NRRL B-543) and Staphylococcus aureus, Gram-ve bacteria Escherichia coli (NRRLB-21), yeasts-Candida albicans (NRRLY-477) and Saccharomyces cercvisiae (NRRL Y-567) and fungs Asperigillus niger (NRRL 599). Screening results revealed that most of the tested compounds possess good antimicrobial activity compared to standard drugs. The highest inhibitory effects against Gram-ve Escherichia coli, Gram+ve Staphylococcus aureus, yeast Candida albicans and fungus Aspergillus niger was displayed by amide (8g) bearing the thiophene moiety. (author)

  4. Evaluating short-term hydro-meteorological fluxes using GRACE-derived water storage changes

    Science.gov (United States)

    Eicker, A.; Jensen, L.; Springer, A.; Kusche, J.

    2017-12-01

    Atmospheric and terrestrial water budgets, which represent important boundary conditions for both climate modeling and hydrological studies, are linked by evapotranspiration (E) and precipitation (P). These fields are provided by numerical weather prediction models and atmospheric reanalyses such as ERA-Interim and MERRA-Land; yet, in particular the quality of E is still not well evaluated. Via the terrestrial water budget equation, water storage changes derived from products of the Gravity Recovery and Climate Experiment (GRACE) mission, combined with runoff (R) data can be used to assess the realism of atmospheric models. In this contribution we will investigate the closure of the water balance for short-term fluxes, i.e. the agreement of GRACE water storage changes with P-E-R flux time series from different (global and regional) atmospheric reanalyses, land surface models, as well as observation-based data sets. Missing river runoff observations will be extrapolated using the calibrated rainfall-runoff model GR2M. We will perform a global analysis and will additionally focus on selected river basins in West Africa. The investigations will be carried out for various temporal scales, focusing on short-term fluxes down to daily variations to be detected in daily GRACE time series.

  5. Hyaluronic acid effect on adipose-derived stem cells. Biological in vitro evaluation.

    Science.gov (United States)

    Moreno, A; Martínez, A; Olmedillas, S; Bello, S; de Miguel, F

    2015-01-01

    To evaluate the in vitro effects of hyaluronic acid (HA) on adipose-derived stem cells (ASC) in order to consider the possibility of their combined used in the treatment of knee arthrosis. The ASC cells were grown both in the presence and absence of AH, and several studies were carried out: proliferation (WST8) and cell viability studies (Alamar Blue® and Trypan Blue), possible chondrogenic differentiation (collagen type 2 expression) by RT-PCR, AH receptor expression (CD44) by flow cytometry and RT-QPCR, and expression of inflammatory and anti-inflammatory factors (IL-6, TGFß, IL-10) by RT-QPCR. The number of ASC significantly increased after 7 days with HA (158±39%, p <0.05). Additionally, the cell viability of the ASC treated with HA after 1, 3, 5 and 7 days was similar to that of the control cells, being considered non-toxic. There were no changes observed in the expression of CD44 and chondrogenic differentiation. TGFß expression was not modified after AH treatment, but there was a 4-fold decrease in IL-6 expression and IL-10 expression increased up to 2-fold compared to control cells. Hyaluronic acid favours ASC proliferation without causing cellular toxicity, and inducing an anti-inflammatory profile in these cells. Hyaluronic acid appears to be a suitable vehicle for the intra-articular administration of mesenchymal stem cells. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  6. New Sorafenib Derivatives: Synthesis, Antiproliferative Activity Against Tumour Cell Lines and Antimetabolic Evaluation

    Directory of Open Access Journals (Sweden)

    Branka Zorc

    2012-01-01

    Full Text Available Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a–e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1, 4-chloro-pyridine-2-carboxamides 2a–e, 4-(4-aminophenoxy-pyridine-2-carboxamides 3a–e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethylphenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a–e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a–e (IC50 = 1-4.3 μmol·L−1. Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity.

  7. Evaluation of the Cytotoxicity of Structurally Correlated p-Menthane Derivatives

    Directory of Open Access Journals (Sweden)

    Luciana Nalone Andrade

    2015-07-01

    Full Text Available Compounds isolated from essential oils play an important role in the prevention and treatment of cancer. Monoterpenes are natural products, and the principal constituents of many essential oils. The aim of this study was to investigate the cytotoxic potential of p-menthane derivatives. Additionally, analogues of perillyl alcohol, a monoterpene with known anticancer activity, were evaluated to identify the molecular characteristics which contribute to their cytotoxicity, which was tested against OVCAR-8, HCT-116, and SF-295 human tumor cell lines, using the MTT assay. The results of this study showed that (−-perillaldehyde 8,9-epoxide exhibited the highest percentage inhibition of cell proliferation (GI = 96.32%–99.89%. Perillyl alcohol exhibited high cytotoxic activity (90.92%–95.82%, while (+-limonene 1,2-epoxide (GI = 58.48%–93.10%, (−-perillaldehyde (GI = 59.28%–83.03%, and (−-8-hydroxycarvotanacetone (GI = 61.59%–94.01% showed intermediate activity. All of the compounds tested were less cytotoxic than perillyl alcohol, except (−-perillaldehyde 8,9-epoxide (IC50 = 1.75–1.03 µL/mg. In general, replacement of C-C double bonds by epoxide groups in addition to the aldehyde group increases cytotoxicity. Furthermore, stereochemistry seems to play an important role in cytotoxicity. We have demonstrated the cytotoxic influence of chemical substituents on the p-menthane structure, and analogues of perillyl alcohol.

  8. Success Evaluation of Pulpotomy in Primary Molars with Enamel Matrix Derivative: a Pilot Study

    Directory of Open Access Journals (Sweden)

    Fatemeh Mazhari

    2016-06-01

    Full Text Available Aim: To investigate the effect of Emdogain gel (EMD in pulpotomized primary molars and its clinical and radiographic outcomes. Methods and Materials: In this   study, 18 lower second primary molars of nine children were treated by   pulpotomy. The teeth were randomly assigned to the EMD (experimental and Formocresol (control groups in each patient (split mouth. Following removal of the coronal pulp and haemostasis, the pulp stumps were covered with Emdogain gel in the experimental group followed by application of resin-modified glass ionomer cement over the gel. In the control group, Formocresol (FC was placed with a cotton pellet over the pulp stumps. Lastly, the teeth in both groups were restored with stainless steel crowns. Results: Nine children referred with clinical failure before/at two months follow up. The radiographic evaluation revealed furcation involvement and extensive radicular radiolucency in molars treated with Emdogain gel. Conclusion: The present study showed the failure of enamel matrix derivative in pulpotomy of primary molars; therefore, we do not recommend using Emdogain as a pulpotomy agent for treatment of cariously exposed primary teeth

  9. Low pressure carbonylation of benzyl chloride = Die carbonylierung von benzylchlorid bei niedrigen drücken

    OpenAIRE

    Luggenhorst, H.J.; Westerterp, K.R.

    1986-01-01

    For carbonylations, metal carbonyls, particularly cobalt and iron carbonyls, are often used as catalysts. These reactions take place under rather drastic reaction conditions, e.g. 200–300 °C and 60–100 MPa. In some patents it is stated that similar reactions using the same catalysts can also be carried out under rather mild reaction conditions, such as 0–100 °C and 0–2.5 MPa. We studied the conversion of benzyl chloride to phenyl acetic methyl ester in a semi-batch reactor in which one of the...

  10. Intramolecular addition of benzylic radicals onto ketenimines. Synthesis of 2-alkylindoles.

    Science.gov (United States)

    Alajarín, Mateo; Vidal, Angel; Ortín, María-Mar

    2003-12-07

    The inter- and intramolecular addition of free radicals onto ketenimines is studied. All the attempts to add intermolecularly several silicon, oxygen or carbon centered radicals to N-(4-methylphenyl)-C,C-diphenyl ketenimine were unsuccessful. In contrast, the intramolecular addition of benzylic radicals, generated from xanthates, onto the central carbon of a ketenimine function with its N atom linked to the ortho position of the aromatic ring occurred under a variety of reaction conditions. These intramolecular cyclizations provide a novel radical-mediated synthesis of 2-alkylindoles.

  11. Gold( i )-catalysed dehydrative formation of ethers from benzylic alcohols and phenols

    KAUST Repository

    Veenboer, Richard M. P.

    2015-01-01

    © The Royal Society of Chemistry 2015. We report the cross-dehydrative reaction of two alcohols to form unsymmetrical ethers using NHC-gold(i) complexes (NHC = N-heterocyclic carbene). Our progress in developing this reaction into a straightforward procedure is discussed in detail. The optimised methodology proceeds under mild reaction conditions and produces water as the sole by-product. The synthetic utility of this environmentally benign methodology is exemplified by the formation of a range of new ethers from readily available phenols bearing electron withdrawing substituents and secondary benzylic alcohols with various substituents. Finally, we present experimental results to account for the chemoselectivity obtained in these reactions.

  12. Structure and properties of poly(benzyl acrylate) synthesized under microwave energy

    Energy Technology Data Exchange (ETDEWEB)

    Oberti, Tamara G. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA), Facultad de Ciencias Exactas, Universidad Nacional de La Plata-CONICET Casilla de Correo 16, Sucursal 4, 1900 La Plata (Argentina); Laboratorio de Estudio de Compuestos Organicos (LADECOR), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata (Argentina); Schiavoni, M. Mercedes [Laboratorio de Estudio de Compuestos Organicos (LADECOR), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 1900 La Plata (Argentina); Cortizo, M. Susana [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA), Facultad de Ciencias Exactas, Universidad Nacional de La Plata-CONICET Casilla de Correo 16, Sucursal 4, 1900 La Plata (Argentina)], E-mail: gcortizo@inifta.unlp.edu.ar

    2008-05-15

    Benzyl acrylate was polymerized under microwave irradiation using radical initiation (benzoyl peroxide, BP). The effect of the concentration of BP and power irradiation on the conversion, average molecular weights and the polydispersity index (M{sub w}/M{sub n}) were investigated. The {sup 1}H NMR and {sup 13}C NMR spectra analysis showed tendency to syndiotacticity and branched polymers were obtained at high conversion of reactions. A significant enhancement of the rates of polymerization and similar thermodynamic behavior, as compared with those obtained under thermal conditions was found.

  13. Ultrasonicated Synthesis of N-Benzyl-2,3-substituted Morpholines, via the Mitsunobu Diol Cyclisation

    Directory of Open Access Journals (Sweden)

    B. Jayachandra Reddy

    2010-01-01

    Full Text Available A facile five step synthesis of N-benzyl-2,3-substituted morpholines (i-iii was performed. The key steps were microwave assisted Friedel-crafts acylation and diol cyclization carried out via an ultra sonication of Mitsunobu reaction using DEAD (diethylazodicarboxylate, TPP in THF for 1 h. The morpholine products were generated as diasteriomers (ii andiii which has been separated by the column chromatography to good yield. The structure of compounds (i-iii has been characterized by the spectral and chemical studies.

  14. Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

    Directory of Open Access Journals (Sweden)

    Paul P. Kelly

    2015-09-01

    Full Text Available Cytochrome P450 monooxygenases are useful biocatalysts for C–H activation, and there is a need to expand the range of these enzymes beyond what is naturally available. A panel of 93 variants of active self-sufficient P450cam[Tyr96Phe]-RhFRed fusion enzymes with a broad diversity in active site amino acids was developed by screening a large mutant library of 16,500 clones using a simple, highly sensitive colony-based colorimetric screen against indole. These mutants showed distinct fingerprints of activity not only when screened in oxidations of substituted indoles but also for unrelated oxidations such as benzylic hydroxylations.

  15. Comparative substoichiometric extraction of zinc with potassium salts of ethyl, propyl, butyl, pentyl and benzyl xanthates

    International Nuclear Information System (INIS)

    Chandrasekhar Reddy, P.; Rangamannar, P.

    1995-01-01

    The comparative extractability of zinc with potassium salts of ethyl, propyl, butyl, pentyl, and benzyl xanthates from the pH range of 3.5-9.0 into chloroform has been studied, employing a sensitive and rapid substoichiometric radiochemical method. The extent of reproducibility was tested in each case. The effect of associated ions on the extraction was studied. The amount of zinc present in the standard solutions was determined employing each xanthate separately. The zinc content present in geological water samples in and around Tirupati was determined by the method developed and compared with the values obtained by Atomic Absorption Spectrophotometry. (author) 4 refs.; 3 figs.; 4 tabs

  16. Comparative substoichiometric extraction of cadmium with potassium salts of ethyl, propyl, butyl, pentyl and benzyl xanthates

    International Nuclear Information System (INIS)

    Chandrasekhar Reddy, P.; Rangamannar, B.

    1995-01-01

    A comparative study of the extractability of cadmium with potassium salts of ethyl, propyl, butyl, pentyl and benzyl xanthates into chloroform and a mixture of 1:4 pyridine and ethyl acetate from pH 1-7 buffers and sodium formate media, respectively, has been carried out employing an accurate and highly sensitive substoichiometric radiochemical method. The effect of foreign ions on the extractability was studied. The method developed was utilized for the determination of cadmium content in standard as well as in geological water samples. (author) 4 refs.; 5 figs.; 3 tabs

  17. S-Substituted cysteine derivatives and thiosulfinate formation in Petiveria alliacea-part II.

    Science.gov (United States)

    Kubec, Roman; Kim, Seokwon; Musah, Rabi A

    2002-11-01

    Three cysteine derivatives, (R)-S-(2-hydroxyethyl)cysteine, together with (R(S)R(C))- and (S(S)R(C))-S-(2-hydroxyethyl)cysteine sulfoxides, have been isolated from the roots of Petiveria alliacea. Furthermore, three additional amino acids, S-methyl-, S-ethyl-, and S-propylcysteine derivatives, were detected. They were present only in trace amounts (<3 microg g(-1) fr. wt), precluding determination of their absolute configurations and oxidation states. In addition, four thiosulfinates, S-(2-hydroxyethyl) (2-hydroxyethane)-, S-(2-hydroxyethyl) phenylmethane-, S-benzyl (2-hydroxyethane)- and S-benzyl phenylmethanethiosulfinates, have been found in a homogenate of the roots. The formation pathways of various benzyl/phenyl-containing compounds previously found in the plant were also discussed.

  18. Basic evaluation of 67Ga labeled digoxin derivative as a metal-labeled bifunctional radiopharmaceutical

    International Nuclear Information System (INIS)

    Fujibayashi, Yasuhisa; Konishi, Junji; Takemura, Yasutaka; Taniuchi, Hideyuki; Iijima, Naoko; Yokoyama, Akira.

    1993-01-01

    To develop metal-labeled digoxin radiopharmaceuticals with affinity with anti-digoxin antibody as well as Na + , K + -ATPase, a digoxin derivative conjugated with deferoxamine was synthesized. The derivative had a high binding affinity with 67 Ga at deferoxamine introduced to the terminal sugar ring of digoxin. The 67 Ga labeled digoxin derivative showed enough in vitro binding affinity and selectivity to anti-digoxin antibody as well as Na + , K + -ATPase. The 67 Ga labeled digoxin derivative is considered to be a potential metal-labeled bifunctional radiopharmaceutical for digoxin RIA as well as myocardial Na + , K + -ATPase imaging. (author)

  19. Evaluation of nefazodone-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sujeong, E-mail: crystalee@gmail.com [Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-343 (Korea, Republic of); Lee, Hyang-Ae, E-mail: hyangaelee@gmail.com [Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-343 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 110-799 (Korea, Republic of); Human and Environmental Toxicology Program, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-350 (Korea, Republic of); Choi, Sung Woo, E-mail: djmaya@snu.ac.kr [Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 110-799 (Korea, Republic of); Kim, Sung Joon, E-mail: sjoonkim@snu.ac.kr [Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 110-799 (Korea, Republic of); Kim, Ki-Suk, E-mail: idkks00@gmail.com [Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-343 (Korea, Republic of); Human and Environmental Toxicology Program, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon 305-350 (Korea, Republic of)

    2016-04-01

    The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), which express the major cardiac ion channels and recapitulate spontaneous mechanical and electrical activities, may provide a possible solution for the lack of in vitro human-based cardiotoxicity testing models. Cardiotoxicity induced by the antidepressant nefazodone was previously revealed to cause an acquired QT prolongation by hERG channel blockade. To elucidate the cellular mechanisms underlying the cardiotoxicity of nefazodone beyond hERG, its effects on cardiac action potentials (APs) and ion channels were investigated using hiPSC-CMs with whole-cell patch clamp techniques. In a proof of principle study, we examined the effects of cardioactive channel blockers on the electrophysiological profile of hiPSC-CMs in advance of the evaluation of nefazodone. Nefazodone dose-dependently prolonged the AP duration at 90% (APD{sub 90}) and 50% (APD{sub 50}) repolarization, reduced the maximum upstroke velocity (dV/dt{sub max}) and induced early after depolarizations. Voltage-clamp studies of hiPSC-CMs revealed that nefazodone inhibited various voltage-gated ion channel currents including I{sub Kr}, I{sub Ks}, I{sub Na}, and I{sub Ca}. Among them, I{sub Kr} and I{sub Na} showed relatively higher sensitivity to nefazodone, consistent with the changes in the AP parameters. In summary, hiPSC-CMs enabled an integrated approach to evaluate the complex interactions of nefazodone with cardiac ion channels. These results suggest that hiPSC-CMs can be an effective model for detecting drug-induced arrhythmogenicity beyond the current standard assay of heterologously expressed hERG K{sup +} channels. - Highlights: • Nefazodone prolonged APD and decreased upstroke velocity of APs in hiPSC-CMs. • Nefazodone inhibited cardiac ion channels, especially I{sub Kr} and I{sub Na}, in hiPSC-CMs. • Nefazodone-induced AP changes are mainly the result of I{sub Kr} and I{sub Na} inhibition

  20. Novel derivatives of aclacinomycin A block cancer cell migration through inhibition of farnesyl transferase.

    Science.gov (United States)

    Magi, Shigeyuki; Shitara, Tetsuo; Takemoto, Yasushi; Sawada, Masato; Kitagawa, Mitsuhiro; Tashiro, Etsu; Takahashi, Yoshikazu; Imoto, Masaya

    2013-03-01

    In the course of screening for an inhibitor of farnesyl transferase (FTase), we identified two compounds, N-benzyl-aclacinomycin A (ACM) and N-allyl-ACM, which are new derivatives of ACM. N-benzyl-ACM and N-allyl-ACM inhibited FTase activity with IC50 values of 0.86 and 2.93 μM, respectively. Not only ACM but also C-10 epimers of each ACM derivative failed to inhibit FTase. The inhibition of FTase by N-benzyl-ACM and N-allyl-ACM seems to be specific, because these two compounds did not inhibit geranylgeranyltransferase or geranylgeranyl pyrophosphate (GGPP) synthase up to 100 μM. In cultured A431 cells, N-benzyl-ACM and N-allyl-ACM also blocked both the membrane localization of H-Ras and activation of the H-Ras-dependent PI3K/Akt pathway. In addition, they inhibited epidermal growth factor (EGF)-induced migration of A431 cells. Thus, N-benzyl-ACM and N-allyl-ACM inhibited EGF-induced migration of A431 cells by inhibiting the farnesylation of H-Ras and subsequent H-Ras-dependent activation of the PI3K/Akt pathway.

  1. EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 20, Revision 3 (FGE.20Rev3): Benzyl alcohols, benzaldehydes, a related acetal, benzoic acids, and related esters from chemical groups 23 and 30

    DEFF Research Database (Denmark)

    Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to consider in this revision 3 of Flavouring Group Evaluation 20, the SCF Opinion on benzoic acid. Furthermore information on stereoisomeric composition for two...... Regulation (EC) No 1565/2000. None of the substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern...

  2. Synthesis of novel (-)-epicatechin derivatives as potential endothelial GPER agonists: Evaluation of biological effects.

    Science.gov (United States)

    Sarmiento, Viviana; Ramirez-Sanchez, Israel; Moreno-Ulloa, Aldo; Romero-Perez, Diego; Chávez, Daniel; Ortiz, Miguel; Najera, Nayelli; Correa-Basurto, Jose; Villarreal, Francisco; Ceballos, Guillermo

    2018-02-15

    To potentially identify proteins that interact (i.e. bind) and may contribute to mediate (-)-epicatechin (Epi) responses in endothelial cells we implemented the following strategy: 1) synthesis of novel Epi derivatives amenable to affinity column use, 2) in silico molecular docking studies of the novel derivatives on G protein-coupled estrogen receptor (GPER), 3) biological assessment of the derivatives on NO production, 4) implementation of an immobilized Epi derivative affinity column and, 5) affinity column based isolation of Epi interacting proteins from endothelial cell protein extracts. For these purposes, the Epi phenol and C3 hydroxyl groups were chemically modified with propargyl or mesyl groups. Docking studies of the novel Epi derivatives on GPER conformers at 14 ns and 70 ns demostrated favorable thermodynamic interactions reaching the binding site. Cultures of bovine coronary artery endothelial cells (BCAEC) treated with Epi derivatives stimulated NO production via Ser1179 phosphorylation of eNOS, effects that were attenuated by the use of the GPER blocker, G15. Epi derivative affinity columns yielded multiple proteins from BCAEC. Proteins were electrophoretically separated and inmmunoblotting analysis revealed GPER as an Epi derivative binding protein. Altogether, these results validate the proposed strategy to potentially isolate and identify novel Epi receptors that may account for its biological activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Development and application of a validated stability-indicating HPLC method for simultaneous determination of granisetron hydrochloride, benzyl alcohol and their main degradation products in parenteral dosage forms.

    Science.gov (United States)

    Hewala, Ismail; El-Fatatre, Hamed; Emam, Ehab; Mubrouk, Mokhtar

    2010-06-30

    A simple, rapid and sensitive reversed phase high performance liquid chromatographic method using photodiode array detection was developed and validated for the simultaneous determination of granisetron hydrochloride, benzyl alcohol, 1-methyl-1H-indazole-3-carboxylic acid (the main degradation product of granisetron) and benzaldehyde (the main degradation product of benzyl alcohol) in granisetron injections. The separation was achieved on Hypersil BDS C8 (250 mm x 4.6 mm i.d., 5 microm particle diameter) column using a mobile phase consisted of acetonitrile:0.05 M KH(2)PO(4):triethylamine (22:100:0.15) adjusted to pH 4.8. The column was maintained at 25 degrees C and 20 microL of solutions was injected. Photodiode array detector was used to test the peak purity and the chromatograms were extracted at 210 nm. Naphazoline hydrochloride was used as internal standard. The method was validated with respect to specificity, linearity, accuracy, precision, limit of quantitation and limit of detection. The validation acceptance criteria were met in all cases. Identification of the pure peaks was carried out using library match programmer and wavelengths of derivative optima of the spectrograms of the peaks. The method was successfully applied to the determination of the investigated drugs and their degradation products in different batches of granisetron injections. The method was proved to be sensitive for the determination down to 0.03 and 0.01% of granisetron degradation product and benzaldehyde, respectively, which are far below the compendia limits for testing these degradation products in their corresponding intact drugs. Copyright 2010 Elsevier B.V. All rights reserved.

  4. Evaluating satellite-derived long-term historical precipitation datasets for drought monitoring in Chile

    Science.gov (United States)

    Zambrano, Francisco; Wardlow, Brian; Tadesse, Tsegaye; Lillo-Saavedra, Mario; Lagos, Octavio

    2017-04-01

    Precipitation is a key parameter for the study of climate change and variability and the detection and monitoring of natural disaster such as drought. Precipitation datasets that accurately capture the amount and spatial variability of rainfall is critical for drought monitoring and a wide range of other climate applications. This is challenging in many parts of the world, which often have a limited number of weather stations and/or historical data records. Satellite-derived precipitation products offer a viable alternative with several remotely sensed precipitation datasets now available with long historical data records (+30years), which include the Climate Hazards Group InfraRed Precipitation with Station (CHIRPS) and Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks-Climate Data Record (PERSIANN-CDR) datasets. This study presents a comparative analysis of three historical satellite-based precipitation datasets that include Tropical Rainfall Measuring Mission (TRMM) Multi-satellite Precipitation Analysis (TMPA) 3B43 version 7 (1998-2015), PERSIANN-CDR (1983-2015) and CHIRPS 2.0 (1981-2015) over Chile to assess their performance across the country and for the case of the two long-term products the applicability for agricultural drought were evaluated when used in the calculation of commonly used drought indicator as the Standardized Precipitation Index (SPI). In this analysis, 278 weather stations of in situ rainfall measurements across Chile were initially compared to the satellite data. The study area (Chile) was divided into five latitudinal zones: North, North-Central, Central, South-Central and South to determine if there were a regional difference among these satellite products, and nine statistics were used to evaluate their performance to estimate the amount and spatial distribution of historical rainfall across Chile. Hierarchical cluster analysis, k-means and singular value decomposition were used to analyze

  5. Clinical evaluation of the efficacy of removing microorganisms to disinfect patient-derived dental impressions.

    Science.gov (United States)

    Egusa, Hiroshi; Watamoto, Takao; Matsumoto, Takuya; Abe, Keiko; Kobayashi, Munemasa; Akashi, Yoshihiro; Yatani, Hirofumi

    2008-01-01

    Disinfection of dental impressions is an indispensable procedure for the control of cross-contamination; however, there is limited information on the efficacy of disinfection under clinical conditions. The objective of this study was to clinically evaluate the disinfection efficacy of commercially available agents in removing oral pathogens from patient-derived impressions. Impressions from 54 patients were divided into groups and either left undisinfected or underwent 1 of 5 disinfection treatments: (1) 2% glutaraldehyde (GA), (2) 1% sodium hypochlorite (SH), (3) 0.25% benzalkonium chloride (BC), (4) 1 ppm ozonated water (OW), or (5) the Hygojet/MD520 system (HJ). An impression culture technique using a brain heart infusion agar medium was used to visualize the microbial contamination on the surface of the impression cultures. The persistent presence of oral pathogens on the impression cultures was examined using selective isolation agar plates. The isolation frequencies of streptococci, staphylococci, Candida, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa species from undisinfected impressions were 100%, 55.6%, 25.9%, 25.9% and 5.6%, respectively. Disinfection with HJ and BC removed the microorganisms with the greatest efficacy, followed by GA, SH, and OW. Potential bacterial contamination could be detected even after disinfection had been performed. Combined use of BC plus GA or SH removed oral pathogens almost completely from dental impressions. This investigation showed that potential contaminants are still present, even after general disinfection procedures. Therefore, either HJ or the combined use of BC with GA or SH is recommended for clinical and laboratory use.

  6. Evaluation of p53 Polymorphism in Patients with Pannus-Derived Prosthetic Dysfunction.

    Science.gov (United States)

    Gursoy, Mustafa Ozan; Karakoyun, Suleyman; Kalcik, Macit; Yesin, Mahmut; Gunduz, Sabahattin; Astarcioğlu, Mehmet Ali; Oğuz, Ali Emrah; Ozkan, Mehmet

    2015-09-01

    Prosthetic valve dysfunction (PVD) due to pannus formation is considered to occur due to a bioreaction to prosthetic material. The p53 gene plays a critical role in apoptosis and cell proliferation. p53 Arg72Pro polymorphism has been found to be associated with coronary stent restenosis, but has not yet been studied in prosthetic heart valve dysfunction. The study aim was to evaluate the association between pannus-derived PVD and p53 G72C(Arg72Pro) polymorphism. This single-center, prospective study included 25 patients (20 females, five males; mean age 45.6 +/- 12.5 years; group 1) who underwent redo valve surgery due to PVD, and 49 age- and gender-matched control patients (44 females, five males; mean age 47.3 +/- 12.2 years; group 2) with normofunctional prostheses. The prostheses were examined using transthoracic and transesophageal echocardiography. Analyses of p53 G72C(Arg72Pro) polymorphism were performed using Roche LightCyler 2.0 Real-time polymerase chain reaction. The most common location of replaced valves was the mitral position in both groups (88% and 89.8%, respectively). In group 1, normal alleles (GG) were observed in 12 patients (48%), while one patient (4%) showed a homozygous mutation (GC) and 12 patients (48%) showed a heterozygous mutation (CC). In group 2, 21 patients (42.9%) had normal alleles (GG), while four (8.2%) had a homozygous mutation (CC) and 24 (48.9%) had a heterozygous mutation (GC). No significant difference was observed between the groups with regards to p53 Arg72Pro polymorphism (p = 0.769). In patients with prosthetic valves, the underlying mechanism behind pannus formation is unrelated to p53 Arg72Pro polymorphism.

  7. Synthesis and evaluation of a radioiodinated lumiracoxib derivative for the imaging of cyclooxygenase-2 expression

    International Nuclear Information System (INIS)

    Kuge, Yuji; Obokata, Naoyuki; Kimura, Hiroyuki; Katada, Yumiko; Temma, Takashi; Sugimoto, Yukihiko; Aita, Kazuki; Seki, Koh-ichi; Tamaki, Nagara; Saji, Hideo

    2009-01-01

    Introduction: Despite extensive attempts to develop cyclooxygenase (COX)-2 imaging radiotracers, no suitable positron emission tomography (PET)/single photon emission computed tomography (SPECT) tracers are currently available for in vivo imaging of COX-2 expression. The aims of this study were to synthesize and evaluate a radioiodinated derivative of lumiracoxib, 2-[(2-fluoro-6-iodophenyl)-amino]-5-methylphenylacetic acid (FIMA), which is structurally distinct from other drugs in the class and has weakly acidic properties, as a SPECT tracer for imaging COX-2 expression. Methods: The COX inhibitory potency was assessed by measuring COX-catalyzed oxidation with hydrogen peroxide. Cell uptake characteristics of 125 I-FIMA were assessed in control and linterfero/interferon-γ-stimulated macrophages. The biodistribution of 125 I-FIMA was determined by the ex vivo tissue counting method in rats. Results: The COX-2 inhibitory potency of FIMA (IC 50 =2.46 μM) was higher than that of indomethacin (IC 50 =20.9 μM) and was comparable to lumiracoxib (IC 50 =0.77 μM) and diclofenac (IC 50 =0.98 μM). The IC 50 ratio (COX-1/COX-2=182) indicated FIMA has a high isoform selectivity for COX-2. 125 I-FIMA showed a significantly higher accumulation in COX-2 induced macrophages than in control macrophages, which decreased with nonradioactive FIMA in a concentration dependent manner. The biodistribution study showed rapid clearance of 125 I-FIMA from the blood and most organs including the liver and kidneys. No significant in vivo deiodination was observed with radioiodinated FIMA. Conclusions: FIMA showed high inhibitory potency and selectivity for COX-2. Radioiodinated FIMA showed specific accumulation into COX-2 induced macrophages, no significant in vivo deiodination and rapid blood clearance. Radioiodinated FIMA deserves further investigation as a SPECT radiopharmaceutical for imaging COX-2 expression.

  8. Synthesis and evaluation of a radioiodinated lumiracoxib derivative for the imaging of cyclooxygenase-2 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kuge, Yuji [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638 (Japan)], E-mail: kuge@med.hokudai.ac.jp; Obokata, Naoyuki; Kimura, Hiroyuki; Katada, Yumiko; Temma, Takashi [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Sugimoto, Yukihiko [Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Aita, Kazuki [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Central Institute of Isotope Science, Hokkaido University, Sapporo 060-8638 (Japan); Seki, Koh-ichi [Central Institute of Isotope Science, Hokkaido University, Sapporo 060-8638 (Japan); Tamaki, Nagara [Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638 (Japan); Saji, Hideo [Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)

    2009-11-15

    Introduction: Despite extensive attempts to develop cyclooxygenase (COX)-2 imaging radiotracers, no suitable positron emission tomography (PET)/single photon emission computed tomography (SPECT) tracers are currently available for in vivo imaging of COX-2 expression. The aims of this study were to synthesize and evaluate a radioiodinated derivative of lumiracoxib, 2-[(2-fluoro-6-iodophenyl)-amino]-5-methylphenylacetic acid (FIMA), which is structurally distinct from other drugs in the class and has weakly acidic properties, as a SPECT tracer for imaging COX-2 expression. Methods: The COX inhibitory potency was assessed by measuring COX-catalyzed oxidation with hydrogen peroxide. Cell uptake characteristics of {sup 125}I-FIMA were assessed in control and linterfero/interferon-{gamma}-stimulated macrophages. The biodistribution of {sup 125}I-FIMA was determined by the ex vivo tissue counting method in rats. Results: The COX-2 inhibitory potency of FIMA (IC{sub 50}=2.46 {mu}M) was higher than that of indomethacin (IC{sub 50}=20.9 {mu}M) and was comparable to lumiracoxib (IC{sub 50}=0.77 {mu}M) and diclofenac (IC{sub 50}=0.98 {mu}M). The IC{sub 50} ratio (COX-1/COX-2=182) indicated FIMA has a high isoform selectivity for COX-2. {sup 125}I-FIMA showed a significantly higher accumulation in COX-2 induced macrophages than in control macrophages, which decreased with nonradioactive FIMA in a concentration dependent manner. The biodistribution study showed rapid clearance of {sup 125}I-FIMA from the blood and most organs including the liver and kidneys. No significant in vivo deiodination was observed with radioiodinated FIMA. Conclusions: FIMA showed high inhibitory potency and selectivity for COX-2. Radioiodinated FIMA showed specific accumulation into COX-2 induced macrophages, no significant in vivo deiodination and rapid blood clearance. Radioiodinated FIMA deserves further investigation as a SPECT radiopharmaceutical for imaging COX-2 expression.

  9. Evaluation of a dental pulp-derived cell sheet cultured on amniotic membrane substrate.

    Science.gov (United States)

    Honjo, Ken-ichi; Yamamoto, Toshiro; Adachi, Tetsuya; Amemiya, Takeshi; Mazda, Osam; Kanamura, Narisato; Kita, Masakazu

    2015-01-01

    Mesenchymal stem cells (MSC) are transplanted for periodontal tissue regeneration, and the periodontal ligament (PDL) is regenerated using a cultured cell sheet. This cultured cell sheet is prepared using PDL-derived cells, growth factors, and amniotic membrane (AM). Dental pulp (DP)-derived cells can be easily obtained from extracted wisdom teeth, proliferate rapidly, and are less susceptible to bacterial infection than PDL-derived cells. Thus, to prepare a novel cell sheet, DP-derived cells were cultured on AM as a culture substrate for immunohistochemical examination. Wisdom teeth extracted from three adults were cut along the cement-enamel border. DP tissue was collected, minced, and primarily cultured. After three or four passage cultures, DP-derived cells were cultured on AM, followed by hematoxylin-eosin (H-E) and immunofluorescence staining. DP-derived cells cultured on AM formed a layered structure. Cells positive for vimentin, Ki-67, ZO-1, desmoplakin, CD29, 44, 105 or 146, STRO-1, collagen IV or VII or laminin 5 or α5 chain were localized. DP-derived cells proliferated on AM, while retaining the properties of DP, which allowed the cultured cell sheet to be prepared. In addition, the cultured cell sheet contained MSC, which suggests its potential application in periodontal tissue regeneration.

  10. Novel Synthesis and Anti-HIV-1 Activity of 2-Arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (Aryl S-DABOs)

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo

    2007-01-01

    The synthesis and the anti-HIV-1 activity of a series of 2-arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (aryl S-DABOs) are reported. These compounds were synthesized via a coupling reaction of the corresponding 6-benzyl-2-thiouracils with aryl iodides in the presence of neocuproine hydrate...

  11. Metal-free oxidative olefination of primary amines with benzylic C-H bonds through direct deamination and C-H bond activation.

    Science.gov (United States)

    Gong, Liang; Xing, Li-Juan; Xu, Tong; Zhu, Xue-Ping; Zhou, Wen; Kang, Ning; Wang, Bin

    2014-09-14

    An oxidative olefination reaction between aliphatic primary amines and benzylic sp(3) C-H bonds has been achieved using N-bromosuccinimide as catalyst and tert-butyl hydroperoxide as oxidant. The olefination proceeds under mild metal-free conditions through direct deamination and benzylic C-H bond activation, and provides easy access to biologically active 2-styrylquinolines with (E)-configuration.

  12. Rate constants for some electrophilic reactions of benzyl, benzhydryl, and trityl cations in solution

    International Nuclear Information System (INIS)

    Ujdak, R.J.; Jones, R.L.; Dorfman, L.M.

    1976-01-01

    Absolute rate constants have been determined by the pulse radiolysis technique for several electrophilic reactions of the benzyl, the benzhydryl, and the trityl cation in 1,2-dichloroethane solution. The rate constants for the reactions of these carbonium ions with chloride ion, with bromide ion, and with iodide ion are all very nearly the same, namely 6 x 10 10 M -1 s -1 at 24 0 C. The values very likely represent the diffusion controlled limit for the ion combination reactions. The rate constants for the reactions with triethylamine, tri-n-propylamine, and tri-n-butylamine range from 2.0 x 10 9 to 7 x 10 6 M -1 s -1 at 24 0 C. With increasing phenyl substitution, the decreasing trend in the magnitude of the rate constant is consistent with the combined electronic and steric effects. With increasing size of the amine, the decrease in the value of the rate constant seems to indicate that the steric effect predominates. The values of the rate constants for reactions of benzyl and benzhydryl cation with methanol, ethanol, and 2-propanol indicate the following. The rate constant is higher for reaction with the alcohol dimer in solution than with alcohol monomer. The rate constants for reaction with alcohol monomer have values of 1 x 10 8 M -1 s -1 or lower

  13. Preclinical evaluation of the saponin derivative GPI-0100 as an immunostimulating and dose-sparing adjuvant for pandemic influenza vaccines

    NARCIS (Netherlands)

    Liu, Heng; Bungener, Laura; ter Veer, Wouter; Coller, Beth-Ann; Wilschut, Jan; Huckriede, Anke

    2011-01-01

    With the current global influenza vaccine production capacity the large demand for vaccines in case of a pandemic can only be fulfilled when antigen dose sparing strategies are employed. Here we used a murine challenge model to evaluate the potential of GPI-0100, a semi-synthetic saponin derivative,

  14. Safety evaluation of pectin-derived acidic oligosaccharides (pAOS): genotoxicity and sub-chronic studies.

    NARCIS (Netherlands)

    Garthoff, J.A.; Heemskerk, S.; Hempenius, R.A.; Lina, B.A.; Krul, C.A.; Koeman, J.H.; Speijers, G.J.

    2010-01-01

    Pectin-derived acidic oligosaccharides (pAOS) are non-digestible carbohydrates to be used in infant formulae and medical nutrition. To support its safety, the genotoxic potential of pAOS was evaluated. pAOS was not mutagenic in the Ames test. Positive results were obtained in the chromosome

  15. Safety evaluation of pectin-derived acidic oligosaccharides (pAOS): Genotoxicity and sub-chronic studies

    NARCIS (Netherlands)

    Garthoff, J.A.; Heemskerk, S.; Hempenius, R.A.; Lina, B.A.R.; Krul, C.A.M.; Koeman, J.H.; Speijers, G.J.A.

    2010-01-01

    Pectin-derived acidic oligosaccharides (pAOS) are non-digestible carbohydrates to be used in infant formulae and medical nutrition. To support its safety, the genotoxic potential of pAOS was evaluated. pAOS was not mutagenic in the Ames test. Positive results were obtained in the chromosome

  16. Basic evaluation of [sup 67]Ga labeled digoxin derivative as a metal-labeled bifunctional radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Fujibayashi, Yasuhisa; Konishi, Junji (Kyoto Univ. (Japan). Faculty of Medicine); Takemura, Yasutaka; Taniuchi, Hideyuki; Iijima, Naoko; Yokoyama, Akira

    1993-11-01

    To develop metal-labeled digoxin radiopharmaceuticals with affinity with anti-digoxin antibody as well as Na[sup +], K[sup +]-ATPase, a digoxin derivative conjugated with deferoxamine was synthesized. The derivative had a high binding affinity with [sup 67]Ga at deferoxamine introduced to the terminal sugar ring of digoxin. The [sup 67]Ga labeled digoxin derivative showed enough in vitro binding affinity and selectivity to anti-digoxin antibody as well as Na[sup +], K[sup +]-ATPase. The [sup 67]Ga labeled digoxin derivative is considered to be a potential metal-labeled bifunctional radiopharmaceutical for digoxin RIA as well as myocardial Na[sup +], K[sup +]-ATPase imaging. (author).

  17. Sulfonamide and carbamate derivatives of 6-chloropurine: synthesis, characterization and antimicrobial activity evaluation

    Directory of Open Access Journals (Sweden)

    K. Venkata Narayana

    2016-07-01

    Full Text Available A series of new sulfonamide derivatives, 9-(substitutedbenzenesulfonyl-6-chloro-9H-purines 7(a-e and carbamate derivatives, 6-chloro-purine-9-carboxylic acid substituted alkyl/arylester 9(a-d, have been synthesized through an intermediate, sodium salt of 6-chloro-9(H-purine (6 which was prepared by the treatment of 6-chloro-9(H-purine (4 with sodium hydride. Structures of the newly synthesized compounds were elucidated by IR, NMR ( 1H and 13C, mass spectra and elemental analysis. Antimicrobial activity against three bacterial strains and three fungal strains at two different concentrations, 100 and 200 µg/mL including MIC values was investigated. Bio-screening data disclosed that most of the sulfonamide derivatives, 7a, 7c and 7d, and one carbamate derivative 9a showed promising antimicrobial activity having MIC values in the range of 18.0-25.0 µg/mL.

  18. Evaluation of IASI-derived dust aerosol characteristics over the tropical belt

    Science.gov (United States)

    Capelle, V.; Chédin, A.; Siméon, M.; Tsamalis, C.; Pierangelo, C.; Pondrom, M.; Crevoisier, C.; Crepeau, L.; Scott, N. A.

    2014-09-01

    IASI (Infrared Atmospheric Sounder Interferometer)-derived monthly mean infrared (10 μm) dust aerosol optical depth (AOD) and altitude are evaluated against ground-based Aerosol RObotic NETwork of sun photometers (AERONET) measurements of the 500 nm coarse-mode AOD and CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) measurements of altitude at 38 AERONET sites (sea and land) within the tropical belt (30° N-30° S). The period covered extends from July 2007 to June 2013. The evaluation goes through the analysis of Taylor diagrams and box-and-whiskers plots, separating situations over oceanic regions and over land. For the AOD, such an evaluation raises the problem of the difference between the two spectral domains used: infrared for IASI and visible for AERONET. Consequently, the two measurements do not share the same metrics. For that reason, AERONET coarse-mode AOD is first "translated" into IASI-equivalent infrared AOD. This is done by the determination, site by site, of an infrared to visible AOD ratio. Because translating visible coarse-mode AOD into infrared AOD requires accurate knowledge of variables, such as the infrared refractive index or the particle size distribution, quantifying the bias between these two sources of AOD is not straightforward. This problem is detailed in this paper, in particular in Appendix A. For the sites over oceanic regions, the overall AOD temporal correlation comes to 0.86 for 786 items (IASI and AERONET monthly mean bins). The overall normalized standard deviation (i.e. ratio of the standard deviation of the test data (IASI) to that of the reference data (AERONET)) is 0.93, close to the desired value of 1. Over land, essentially desert, correlation is 0.74 for 619 items and the normalized standard deviation is 0.86. This slight but significant degradation over land most probably results from the greater complexity of the surface (heterogeneity, elevation) and, to a lesser extent, to the episodic presence of dust

  19. New oxirane derivatives of 1,4-naphthoquinones and their evaluation against T. cruzi epimastigote forms.

    Science.gov (United States)

    Carneiro, Paula F; do Nascimento, Samara B; Pinto, Antonio V; Pinto, Maria do Carmo F R; Lechuga, Guilherme C; Santos, Dilvani O; dos Santos Júnior, Helvécio M; Resende, Jackson A L C; Bourguignon, Saulo C; Ferreira, Vitor F

    2012-08-15

    New oxirane derivatives were synthesized using six naphthoquinones as the starting materials. Our biological results showed that these oxiranes acted as trypanocidal agents against Trypanosoma cruzi with minimal cytotoxicity in the VERO cell line compared to naphthoquinones. In particular, oxirane derivative 14 showed low cytotoxicity in a mammalian cell line and exhibited better activity against epimastigote forms of T.cruzi than the current drug used to treat Chagas disease, benznidazole. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Synthesis and Antimicrobial Evaluation of Some Novel Thiazole, Pyridone, Pyrazole, Chromene, Hydrazone Derivatives Bearing a Biologically Active Sulfonamide Moiety

    Science.gov (United States)

    Darwish, Elham S.; Abdel Fattah, Azza M.; Attaby, Fawzy A.; Al-Shayea, Oqba N.

    2014-01-01

    This study aimed for the synthesis of new heterocyclic compounds incorporating sulfamoyl moiety suitable for use as antimicrobial agents via a versatile, readily accessible N-[4-(aminosulfonyl)phenyl]-2-cyanoacetamide (3). The 2-pyridone derivatives were obtained via reaction of cyanoacetamide with acetylacetone or arylidenes malononitrile. Cycloaddition reaction of cyanoacetamide with salicyaldehyde furnished chromene derivatives. Diazotization of 3 with the desired diazonium chloride gave the hydrazone derivatives 13a–e. Also, the reactivity of the hydrazone towards hydrazine hydrate to give Pyrazole derivatives was studied. In addition, treatment of 3 with elemental sulfur and phenyl isothiocyanate or malononitrile furnished thiazole and thiophene derivatives respectively. Reaction of 3 with phenyl isothiocyanate and KOH in DMF afforded the intermediate salt 17 which reacted in situ with 3-(2-bromoacetyl)-2H-chromen-2-one and methyl iodide afforded the thiazole and ketene N,S-acetal derivatives respectively. Finally, reaction of 3 with carbon disulfide and 1,3-dibromopropane afforded the N-[4-(aminosulfonyl) phenyl]-2-cyano-2-(1,3-dithian-2-ylidene)acetamide product 22. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis. The compounds were evaluated for both their in vitro antibacterial and antifungal activities and showed promising results. PMID:24445259

  1. Synthesis and Antimicrobial Evaluation of Some Novel Thiazole, Pyridone, Pyrazole, Chromene, Hydrazone Derivatives Bearing a Biologically Active Sulfonamide Moiety

    Directory of Open Access Journals (Sweden)

    Elham S. Darwish

    2014-01-01

    Full Text Available This study aimed for the synthesis of new heterocyclic compounds incorporating sulfamoyl moiety suitable for use as antimicrobial agents via a versatile, readily accessible N-[4-(aminosulfonylphenyl]-2-cyanoacetamide (3. The 2-pyridone derivatives were obtained via reaction of cyanoacetamide with acetylacetone or arylidenes malononitrile. Cycloaddition reaction of cyanoacetamide with salicyaldehyde furnished chromene derivatives. Diazotization of 3 with the desired diazonium chloride gave the hydrazone derivatives 13a–e. Also, the reactivity of the hydrazone towards hydrazine hydrate to give Pyrazole derivatives was studied. In addition, treatment of 3 with elemental sulfur and phenyl isothiocyanate or malononitrile furnished thiazole and thiophene derivatives respectively. Reaction of 3 with phenyl isothiocyanate and KOH in DMF afforded the intermediate salt 17 which reacted in situ with 3-(2-bromoacetyl-2H-chromen-2-one and methyl iodide afforded the thiazole and ketene N,S-acetal derivatives respectively. Finally, reaction of 3 with carbon disulfide and 1,3-dibromopropane afforded the N-[4-(aminosulfonyl phenyl]-2-cyano-2-(1,3-dithian-2-ylideneacetamide product 22. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis. The compounds were evaluated for both their in vitro antibacterial and antifungal activities and showed promising results.

  2. Synthesis of Pyridine and Spiropyridine Derivatives Derived from 2-aminoprop- 1-ene-1,1,3-tricarbonitrile Together with their c-Met Kinase and Antiproliferative Evaluations.

    Science.gov (United States)

    Mohareb, Rafat M; Abouzied, Amr S; Abbas, Nermeen S

    2018-02-07

    Among a wide range of pyridines, 3-cyanopyridines acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the pyridine nucleus were known in the market. The aim of this work was to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. To achieve this goal, our strategy was to synthesize a series of 3-cyanopyridine derivatives using 2-aminoprop-1-ene-1,1,3-tricarbonitrile (1) as the key starting material for many heterocyclization reactions. Muticoponent reactions were adopted using compound 1 to get different pyridine derivatives that were capable for different heterocyclization reactions. Antiproliferative evaluations and c-Met kinase, Pim-1 kinse inhibitions were perform where some compounds gave high activities. Compounds that showed high antiprolifeative activity were tested gor c-Met-independent and the results showed that compounds 5c, 5e, 5f, 7c, 7f and 16d were more active than foretinib. The Pim-1 kinase inhibition activity of some selected compounds showed that compounds 5e and 16c were high potent to inhibit Pim-1 activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Evaluating Lignite-Derived Products (LDPs) for Agriculture - Does Research Inform Practice?

    Science.gov (United States)

    Patti, Antonio; Rose, Michael; Little, Karen; Jackson, Roy; Cavagnaro, Timothy

    2014-05-01

    Lignite-derived products (LDPs), including humic acids and organo-mineral soil conditioners, are being marketed in many parts of the world. They are promoted as plant growth stimulants, additives that improve plant nutrient uptake as well as providing humic materials to improve soil structure and combat soil degradation. There are mixed views regarding the efficacy of these products and there is a lack of scientific studies that verify the efficacy of these products in the field. Anecdotally, agricultural producers become repeat users of the products when they see economic benefits, such as increases in crop yields, while others abandon repeat use when no benefits were seen. In this paper, we present results from a literature meta-analysis1 and a number of field studies that examine the potential for LDPs to improve soil fertility and plant growth. Our findings suggest that complex interactions between LDPs, soil types, environmental conditions and plant species mean that a 'one-size fits all' product or solution is unlikely; and that changes to soil characteristics brought about by LDPs are more apparent over longer time periods than a single cropping season. Most of these studies have not been undertaken in full field trial conditions, where the crop has been grown to harvest. Limited studies in small plots or glass-house conditions often report early benefits. It is not known if these benefits persist. Moreover, the actual composition of these additives may vary significantly and is rarely specified in full. In a study of our own, a small plot experiment evaluated the effect of a single application of a commercial potassium humate product from Victorian lignite on ryegrass and lucerne grown in a sandy, nutrient deficient, low organic matter soil. Treatment resulted in increased shoot growth (up to 33%) of ryegrass during the pasture establishment phase. Root growth was also improved with a 47% increase at 0-10 cm depth and 122% increase at 10-30 cm depth

  4. Evaluation of Optogenetic Electrophysiology Tools in Human Stem Cell-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Susann Björk

    2017-11-01

    Full Text Available Current cardiac drug safety assessments focus on hERG channel block and QT prolongation for evaluating arrhythmic risks, whereas the optogenetic approach focuses on the action potential (AP waveform generated by a monolayer of human cardiomyocytes beating synchronously, thus assessing the contribution of several ion channels on the overall drug effect. This novel tool provides arrhythmogenic sensitizing by light-induced pacing in combination with non-invasive, all-optical measurements of cardiomyocyte APs and will improve assessment of drug-induced electrophysiological aberrancies. With the help of patch clamp electrophysiology measurements, we aimed to investigate whether the optogenetic modifications alter human cardiomyocytes' electrophysiology and how well the optogenetic analyses perform against this gold standard. Patch clamp electrophysiology measurements of non-transduced stem cell-derived cardiomyocytes compared to cells expressing the commercially available optogenetic constructs Optopatch and CaViar revealed no significant changes in action potential duration (APD parameters. Thus, inserting the optogenetic constructs into cardiomyocytes does not significantly affect the cardiomyocyte's electrophysiological properties. When comparing the two methods against each other (patch clamp vs. optogenetic imaging we found no significant differences in APD parameters for the Optopatch transduced cells, whereas the CaViar transduced cells exhibited modest increases in APD-values measured with optogenetic imaging. Thus, to broaden the screen, we combined optogenetic measurements of membrane potential and calcium transients with contractile motion measured by video motion tracking. Furthermore, to assess how optogenetic measurements can predict changes in membrane potential, or early afterdepolarizations (EADs, cells were exposed to cumulating doses of E-4031, a hERG potassium channel blocker, and drug effects were measured at both spontaneous and

  5. Toxicological evaluation of the natural products and some semisynthetic derivatives of Heterotheca inuloides Cass (Asteraceae).

    Science.gov (United States)

    Rodríguez-Chávez, José Luis; Coballase-Urrutia, Elvia; Sicilia-Argumedo, Gloria; Ramírez-Apan, Teresa; Delgado, Guillermo

    2015-12-04

    Heterotheca ineuloides Cass (Asteraceae), popularly known as árnica mexicana, is widely used in Mexican traditional medicine to treat bruises, dermatological problems, rheumatic pains, and other disorders as cancer. The major constituents in H. inuloides are cadinane type sesquiterpenes, flavonoids and phytosterols. Compounds with a cadinane skeleton have been proved to possess cytotoxic activity against human-tumor cell lines and brine shrimp, and display toxic effects in different animal species. Although this plant has been widely used, there is little available information on the safety and toxicity especially of pure compounds. Evaluate the potential toxicity of the natural products isolated from H. inuloides and some semisynthetic derivatives. The toxic aspects of the following natural products isolated from dried flowers of H. inuloides: 7-hydroxy-3,4-dihydrocadalene (1), 7-hydroxycadalene (2), 3,7-dihydroxy-3(4H)-isocadalen-4-one (3), (1R,4R)-1-hydroxy-4H-1,2,3,4- tetrahydrocadalen-15-oic acid (4), D-chiro-inositol (5), quercetin (6), quercetin-3,7,3'-trimethyl ether (7), quercetin-3,7,3',4'-tetramethyl ether (8), eriodictyol-7,4'-dimethyl ether (9), α-spinasterol (10), caryolan-1,9β-diol (11) and 7-(3,3-dimethylallyloxy)-coumarin (12) as well as the toxic aspects of the semisynthetic compounds 7-acetoxy-3,4-dihydrocadalene (13), 7-benzoxy-3,4-dihydrocadalene (14), 7-acetoxycadalene (15), 7-benzoxycadalene (16), quercetin pentaacetate (17), 7-hydroxycalamenene (18), 3,8-dimethyl-5-(1-methylethyl)-1,2-naphthoquinone (19), and 4-isopropyl-1,6-dimethylbenzo[c]oxepine-7,9-dione (20). Toxic activities of compounds were determined by sulforhodamine B (SRB) assay, Artemia salina assay, RAW264.7 macrophage cells. Additionally, the acute toxicity in mouse of compound 1, the major natural sesquiterpene isolated from the acetone extract, was evaluated. The best cytotoxicity activity was observed for mansonone C (19) on K562 cell line with IC50 1.45 ± 0.14 μM, for

  6. Evaluation of some phenothiazine derivatives as corrosion inhibitors for bronze in weakly acidic solution

    International Nuclear Information System (INIS)

    Bostan, Roxana; Varvara, Simona; Găină, Luiza; Mureşan, Liana Maria

    2012-01-01

    Highlights: ► Phenothiazine derivatives are efficient inhibitors for bronze corrosion. ► Potentiodynamic polarization and EIS were used to elucidate inhibition mechanism. ► Adsorption of phenothiazine derivatives on bronze surface obeys Langmuir isotherm. ► A correlation between energy gaps and inhibition efficiencies values was obtained. - Abstract: Four phenothiazine derivatives have been tested as inhibitors for bronze corrosion in a solution containing Na 2 SO 4 and NaHCO 3 (pH 5). Electrochemical investigations (potentiodynamic polarisation and impedance measurements) revealed that all phenothiazine derivatives exert a protective effect against bronze corrosion and, in some cases their inhibition efficiency exceeds 90% at concentration level as low as 75 μM. An adherent layer of organic molecules chemisorbed on bronze surface is responsible for the protective effect of the investigated compounds. Adsorption of phenothiazine derivatives on bronze obeys Langmuir isotherm. Correlation between quantum chemical calculations and inhibition efficiency of the investigated compounds was discussed using DFT method.

  7. Unsteady Vibration Aerodynamic Modeling and Evaluation of Dynamic Derivatives Using Computational Fluid Dynamics

    Directory of Open Access Journals (Sweden)

    Xu Liu

    2015-01-01

    Full Text Available Unsteady aerodynamic system modeling is widely used to solve the dynamic stability problems encountering aircraft design. In this paper, single degree-of-freedom (SDF vibration model and forced simple harmonic motion (SHM model for dynamic derivative prediction are developed on the basis of modified Etkin model. In the light of the characteristics of SDF time domain solution, the free vibration identification methods for dynamic stability parameters are extended and applied to the time domain numerical simulation of blunted cone calibration model examples. The dynamic stability parameters by numerical identification are no more than 0.15% deviated from those by experimental simulation, confirming the correctness of SDF vibration model. The acceleration derivatives, rotary derivatives, and combination derivatives of Army-Navy Spinner Rocket are numerically identified by using unsteady N-S equation and solving different SHV patterns. Comparison with the experimental result of Army Ballistic Research Laboratories confirmed the correctness of the SHV model and dynamic derivative identification. The calculation result of forced SHM is better than that by the slender body theory of engineering approximation. SDF vibration model and SHM model for dynamic stability parameters provide a solution to the dynamic stability problem encountering aircraft design.

  8. Preparation and evaluation of unilamellar liposomes incorporating boron-containing derivatives of cholesterol

    International Nuclear Information System (INIS)

    Feakes, D.A.; Tate, C.C.; Stefanutti, S.J.

    2000-01-01

    The application of boron neutron capture therapy is dependent on the identification and preparation of boron-containing compounds that can be delivered and retained by the tumor cells. Unilamellar liposomes have been investigated as potential tumor-specific delivery vehicles for boron-containing compounds that have no inherent tumor specificity. A series of carborane-containing derivatives of cholesterol have been prepared and incorporated into the bilayer of unilamellar liposomes. The cholesterol derivatives vary in the linker moiety (ester and ether), the chain length between the cholesterol and the carborane substituent, and the identity of the carborane group itself (closo- and nido-). The ability of the boron-containing derivatives of cholesterol to be incorporated into the bilayer of the unilamellar liposomes and the stability of the resulting liposome formulations will be presented. (author)

  9. Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides.

    Science.gov (United States)

    Grošelj, Uroš; Golobič, Amalija; Knez, Damijan; Hrast, Martina; Gobec, Stanislav; Ričko, Sebastijan; Svete, Jurij

    2016-08-01

    The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer's disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase [Formula: see text] ([Formula: see text] values [Formula: see text] and [Formula: see text], respectively).

  10. Design, Synthesis and Biological Evaluation of Novel Bromophenol Derivatives Incorporating Indolin-2-One Moiety as Potential Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Li-Jun Wang

    2015-02-01

    Full Text Available A series of bromophenol derivatives containing indolin-2-one moiety were designed and evaluated that for their anticancer activities against A549, Bel7402, HepG2, HeLa and HCT116 cancer cell lines using MTT assay in vitro. Among them, seven compounds (4g–4i, 5h, 6d, 7a, 7b showed potent activity against the tested five human cancer cell lines. Wound-healing assay demonstrated that compound 4g can be used as a potent compound for inactivating invasion and metastasis by inhibiting the migration of cancer cells. The structure–activity relationships (SARs of bromophenol derivatives had been discussed, which were useful for exploring and developing bromophenol derivatives as novel anticancer drugs.

  11. Developmental and testicular toxicity of butyl benzyl phthalate in the rat and the impact of study design

    NARCIS (Netherlands)

    Piersma AH; Verhoef A; Dormans JAMA; Elvers LH; Valk V de; Biesebeek JD te; Pieters MN; Slob W; LEO

    1999-01-01

    The developmental toxicity of butyl benzyl phthalate was investigated in the rat in an alternative study design using ten treatment groups. The effect of exposure period was studied, and a comparison of reaction to treatment in pregnant versus non-pregnant females was made. The classical data

  12. Nuclear magnetic resonance of D(-)-{alpha}-amino-benzyl penicillin; Ressonancia magnetica nuclear da D(-)-{alpha}-amino-benzil penicilina

    Energy Technology Data Exchange (ETDEWEB)

    Aguiar, Monica R.M.P.; Gemal, Andre L.; San Gil, Rosane A.S. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Quimica; Menezes, Sonia M.C. [PETROBRAS, Rio de Janeiro, RJ (Brazil). Centro de Pesquisas

    1995-12-31

    The development of new drugs from penicillins has induced the study of this substances by nuclear magnetic resonance. Several samples of D(-)-{alpha}-amino-benzyl penicillin were analysed using {sup 13} C NMR techniques in aqueous solution and solid state. Spectral data of this compounds were shown and the results were presented and analysed 7 figs., 4 tabs.

  13. Organocatalytic Enantioselective Pictet-Spengler Approach to Biologically Relevant 1-Benzyl-1,2,3,4-Tetrahydroisoquinoline Alkaloids

    NARCIS (Netherlands)

    Ruiz-Olalla, A.; Würdemann, M.A.; Wanner, M.J.; Ingemann, S.; van Maarseveen, J.H.; Hiemstra, H.

    2015-01-01

    A general procedure for the synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines was developed, based on organocatalytic, regio- and enantioselective Pictet-Spengler reactions (86-92% ee) of N-(o-nitrophenylsulfenyl)-2-arylethyl-amines with arylacetaldehydes. The presence of the

  14. DFT study of benzyl alcohol/TiO2 interfacial surface complex: reaction pathway and mechanism of visible light absorption.

    Science.gov (United States)

    Zhao, Lei; Gu, Feng Long; Kim, Minjae; Miao, Maosheng; Zhang, Rui-Qin

    2017-09-24

    We propose a new pathway for the adsorption of benzyl alcohol on the surface of TiO 2 and the formation of interfacial surface complex (ISC). The reaction free energies and reaction kinetics were thoroughly investigated by density functional calculations. The TiO 2 surfaces were modeled by clusters consisting of 4 Ti atoms and 18 O atoms passivated by H, OH group and H 2 O molecules. Compared with solid-state calculations utilizing the periodicity of the materials, such cluster modeling allows inclusion of the high-order correlation effects that seem to be essential for the adsorption of organic molecules onto solid surfaces. The effects of both acidity and solvation are included in our calculations, which demonstrate that the new pathway is competitive with a previous pathway. The electronic structure calculations based on the relaxed ISC structures reveal that the chemisorption of benzyl alcohol on the TiO 2 surface greatly alters the nature of the frontier molecular orbitals. The resulted reduced energy gap in ISC matches the energy of visible light, showing how the adsorption of benzyl alcohol sensitizes the TiO 2 surface. Graphical Abstract The chemisorption of benzyl alcohol on TiO 2 surface greatly alters the nature of the frontier molecular orbitals and the formed interfacial surface complex can be sensitized by visible light.

  15. Synthesis and receptor binding studies of novel 4,4-disubstituted arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as a new class of σ1 ligands.

    Science.gov (United States)

    Sadeghzadeh, Masoud; Sheibani, Shahab; Ghandi, Mehdi; Daha, Fariba Johari; Amanlou, Massoud; Arjmand, Mohammad; Hasani Bozcheloie, Abolfazl

    2013-06-01

    This study presents the synthesis and biological evaluation of a new series of arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as sigma receptor ligands. It was found that a number of halogen substituted sulfonamides display relatively high and low affinities to σ1 and σ2 receptors, respectively. The σ1 affinities and subtype selectivities of four piperidine derivatives were also found to be generally comparable to those of piperazine analogues. Compared to σ1-Rs compounds with n = 0 and 2, those with n = 1 proved to have optimal length of carbon chain by exhibiting higher affinities. Within this series, the 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine sigma ligand was identified with 96-fold σ1/σ2 selectivity ratio (Kiσ1 = 0.96 ± 0.05 nM and Kiσ2 = 91.8 ± 8.1 nM). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Anthrarobin and its derivatives: evaluation of antibacterial and lipoxygenase inhibition activities

    International Nuclear Information System (INIS)

    Lateef, M.; Iqbal, S.

    2013-01-01

    The antibacterial activity of anthrarobin and its synthesized derivatives 1, 10-dihydoxyanthracen-2-0-acetate (1) and anthracen-1, 2-10-tri-O-acetate (2) is determined against two Gram-negative bacteria (Escherichia coli, Pseudomonas aerogenosa) and two Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) along with the lipoxygenase inhibition activity. Gentamycin (0.3 %) was used as standard antibiotic for antibacterial assay. The minimum inhibitory concentration (MIC) was determined by agar well diffusion method. Anthrarobin showed highest antibacterial activity against all the tested bacteria while anthracen-1, 2-10-tri-0-acetate (2) exhibited 97 % activity against Gram-positive bacteria, Staphylococcus aureus, and; 36 % activity against Gram-negative bacteria Escherichia coli. On the other hand, 1, 10-dihydoxyanthracen-2-0-acetate (1) remained non-significant against all the bacteria tested. When anthrarobin and its derivatives were analyzed for lipoxygenase inhibition studies, only anthrarobin showed weak inhibition activity with IC 5 0 value of 65.2 μM. It is concluded that anthrarobin has significant potential for antibacterial activity as compared to its synthesized derivatives. Structure-activity relationship suggests that numbers of hydroxyl group in anthrarobin may be responsible for antimicrobial activity and the activity decreases with the substitution of acyl groups in synthesized derivatives. (author)

  17. Novel flurbiprofen derivatives with improved brain delivery: synthesis, in vitro and in vivo evaluations.

    Science.gov (United States)

    Zheng, Dan; Shuai, Xiao; Li, Yanping; Zhou, Peng; Gong, Tao; Sun, Xun; Zhang, Zhirong

    2016-09-01

    Tarenflurbil (R-flurbiprofen) was acknowledged as a promising candidate in Alzheimer's disease (AD) therapy. However, the Phase III study of tarenflurbil was extremely restricted by its poor delivery efficiency to the brain. To tackle this problem, the novel carriers for tarenflurbil, racemic flurbiprofen (FLU) derivatives (FLU-D1 and FLU-D2) modified by N,N-dimethylethanolamine-related structures were synthesized and characterized. These derivatives showed good safety level in vitro and they possessed much higher cellular uptake efficiency in brain endothelial cells than FLU did. More importantly, the uptake experiments suggested that they were internalized via active transport mechanisms. Biodistribution studies in rats also illustrated a remarkably enhanced accumulation of these derivatives in the brain. FLU-D2, the ester linkage form of these derivatives, achieved a higher brain-targeting efficiency. Its C max and AUC 0- t were enhanced by 12.09-fold and 4.61-fold, respectively compared with those of FLU. Additionally, it could be hydrolyzed by esterase in the brain to release the parent FLU, which might facilitate its therapeutic effect. These in vitro and in vivo results highlighted the improvement of the brain-targeted delivery of FLU by making use of N,N-dimethylethanolamine ligand, with which an active transport mechanism was involved.

  18. New improved method for evaluation of growth by food related fungi on biologically derived materials

    DEFF Research Database (Denmark)

    Bergenholtz, Karina P.; Nielsen, Per Væggemose

    2002-01-01

    Biologically derived materials, obtained as commercial and raw materials (Polylactate (PLA), Polyhydroxybutyrate (PHB), potato, wheat and corn starch) were tested for their ability to support fungal growth using a modified ASTM G21-96 (American Society for Testing and Materials) standard as well...

  19. Algorithm for Financial Derivatives Evaluation in a Generalized Multi-Heston Model

    Directory of Open Access Journals (Sweden)

    Dan Negura

    2013-02-01

    Full Text Available In this paper we show how could a financial derivative be estimated based on an assumed Multi-Heston model support.Keywords: Euler Maruyama discretization method, Monte Carlo simulation, Heston model, Double-Heston model, Multi-Heston model

  20. EVALUATION OF TIRE-DERIVED FUEL FOR USE IN NITROGEN OXIDE REDUCTION BY REBURNING

    Science.gov (United States)

    Tire-derived fuel (TDF) was tested in a small-scale (44 kW or 150,000 Btu/hr) combustor to determine its feasibility as a fuel for use in reburning for control of nitrogen oxide (NO). TDF was gravity-fed into upward flowing combustion gases from a primary natural gas flame doped ...

  1. Evaluation of AMSR-E derived soil moisture over Australia, /Remote Sensing of Environment

    NARCIS (Netherlands)

    Draper, C.S.; Walker, J.P.; Steinle, P.J.; De Jeu, R.A.M.; Holmes, T.R.H.

    2009-01-01

    This paper assesses remotely sensed near-surface soil moisture over Australia, derived from the passive microwave Advanced Microwave Scanning Radiometer - Earth Observing System (AMSR-E) instrument. Soil moisture fields generated by the AMSR-E soil moisture retrieval algorithm developed at the Vrije

  2. SYNTHESIS AND PHYSICAL-CHEMICAL PROPERTIES OF WATER-SOLUBLE 3-BENZYLXANTHINE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    K. V. Аleksandrova

    2015-04-01

    Full Text Available Introduction Nowadays, research of novel biological active compounds with low toxicity, are carried out among different classes of organic compounds of natural and synthetic genesis. One of the main ways of these studies is search of water-soluble compounds – convenient objects for pharmacological researches. In recent years researchers paid attention to xanthine derivatives, because of their high variativity of possible chemical modification and ability to form different salts with wide spectrum of biological action. Thus, among water-soluble xanthine derivatives were found compounds with pronounced antioxidant, diuretic and analeptic properties. Primary methods of obtaining water-soluble xanthine derivatives are direct interaction of bases with xanthine molecule or insertion basic or acidic residues in positions 7 or 8 of xanthine bicycle. According from the above, search of biologically active compounds among water-soluble substituted xanthines is prospective and actual. The aim of the study was development of synthetic ways of obtaining novel water-soluble derivatives of 3-benzyl-8-methylxanthine and studying their physical and chemical properties. Material and methods Melting points of obtained compounds were determined by capillary method on PTP (M device. ІR-spectra of synthesized compounds were recorded on the Bruker Alpha device (company «Bruker» – Germany on 4000-400 sm-1 with using console ATR (direct insertion of compound. 1Н NMR-spectra were recorded on the Varian Mercury VX-200 device (company «Varian» – USA solvent – (DMSO-d6, internal standart – ТМС. Elemental analysis was made on Elementar Vario L cube device. Chromatoraphic studies were made on the plates Sorbfil-AFV-UV (company «Sobrpolimer» –Russia. Systhems for chromatography: «acetone-propanol-2» in ratio 2:3, «propanol-2-benzene» in ratio 10:1 and exersized in UV-light in wave 200-300 nm. Results and discussion We developed methodic of synthesis

  3. Flurbiprofen benzyl nitrate (NBS-242) inhibits the growth of A-431 human epidermoid carcinoma cells and targets β-catenin.

    Science.gov (United States)

    Nath, Niharika; Liu, Xiaoping; Jacobs, Lloydine; Kashfi, Khosrow

    2013-01-01

    The Wnt/β-catenin/T cell factor (TCF) signaling pathway is important in the development of nonmelanoma skin cancers (NMSCs). Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are chemopreventive agents consisting of a traditional NSAID attached to an NO-releasing moiety through a chemical spacer. Previously we showed that an aromatic spacer enhanced the potency of a particular NO-NSAID compared to an aliphatic spacer. We synthesized an NO-releasing NSAID with an aromatic spacer (flurbiprofen benzyl nitrate, NBS-242), and using the human skin cancer cell line A-431, we evaluated its effects on cell kinetics, Wnt/β-catenin, cyclin D1, and caspase-3. NBS-242 inhibited the growth of A-431 cancer cells, being ~15-fold more potent than flurbiprofen and up to 5-fold more potent than NO-flurbiprofen with an aliphatic spacer, the half maximal inhibitory concentrations (IC50) for growth inhibition being 60 ± 4 μM, 320 ± 20 μM, and 880 ± 65 μM for NBS-242, NO-flurbiprofen, and flurbiprofen, respectively. This effect was associated with inhibition of proliferation, accumulation of cells in the G0/G1 phase of the cell cycle, and an increase in apoptotic cell population. NBS-242 cleaved β-catenin both in the cytoplasm and the nucleus of A-431 cells. NBS-242 activated caspase-3 whose activation was reflected in the cleavage of procaspase-3. To test the functional consequence of β-catenin cleavage, we determined the expression of cyclin D1, a Wnt-response gene. NBS-242 reduced cyclin D1 levels in a concentration dependent manner. These findings establish a strong inhibitory effect of NBS-242 in A-431 human epidermoid carcinoma cells. NBS-242 modulates parameters that are important in determining cellular mass.

  4. Evaluation of the effects of diuron and its derivatives on Lemna gibba using a fluorescence toxicity index.

    Science.gov (United States)

    Dewez, David; Marchand, Mathieu; Eullaffroy, Philippe; Popovic, Radovan

    2002-10-01

    The herbicide diuron (DCMU) [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is largely used in agricultural practices which contribute to water pollution in large areas. Its degradation induced by light or microbial activity is known to be a slow process, and may result in the accumulation of DCMU derivatives in the environment. In this report we used the yield of PSII variable fluorescence of Lemna gibba affected by the DCMU derivatives DCPMU [1-(3,4-dichlorophenyl)-3-methylurea], DCPU [1-(3,4-dichlorophenyl)urea], and DCA [3,4-dichloroaniline] to calculate the fluorescence toxicity index. We found the fluorescence toxicity index to be a useful parameter to evaluate the inhibitory effect on PSII electron transport in L. gibba exposed to DCMU and its derivatives. The variations observed for the inhibitory effect between DCMU and its derivatives seem to be caused by the modification of the dimethylurea group within the DCMU molecule. The fluorescence toxicity index demonstrated a strong quantitative dependency between the inhibitory effect of PSII electron transport and pollutant concentrations. We propose the fluorescence toxicity index to be a useful tool for future bioassays in evaluating the quality of water polluted with herbicides that induce an inhibition to PSII photochemistry. Copyright 2002 Wiley Periodicals, Inc.

  5. Stereoselective synthesis, X-ray analysis, computational studies and biological evaluation of new thiazole derivatives as potential anticancer agents.

    Science.gov (United States)

    Mabkhot, Yahia N; Alharbi, Mohammed M; Al-Showiman, Salim S; Ghabbour, Hazem A; Kheder, Nabila A; Soliman, Saied M; Frey, Wolfgang

    2018-05-11

    The synthesis of new thiazole derivatives is very important because of their diverse biological activities. Also , many drugs containing thiazole ring in their skeletons are available in the market such as Abafungin, Acotiamide, Alagebrium, Amiphenazole, Brecanavir, Carumonam, Cefepime, and Cefmatilen. Ethyl cyanoacetate reacted with phenylisothiocyanate, chloroacetone, in two different basic mediums to afford the thiazole derivative 6, which reacted with dimethylformamide- dimethyl acetal in the presence of DMF to afford the unexpected thiazole derivative 11. The structures of the thiazoles 6 and 11 were optimized using B3LYP/6-31G(d,p) method. The experimentally and theoretically geometric parameters agreed very well. Also, the natural charges at the different atomic sites were predicted. HOMO and LUMO demands were discussed. The anticancer activity of the prepared compounds was evaluated and showed moderate activity. Synthesis of novel thiazole derivatives was done. The structure was established using X-ray and spectral analysis. Optimized molecular structures at the B3LYP/6-31G(d,p) level were investigated. Thiazole derivative 11 has more electropositive S-atom than thiazole 6. The HOMO-LUMO energy gap is lower in the former compared to the latter. The synthesized compounds showed moderate anticancer activity.

  6. Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

    Science.gov (United States)

    Shah, Sandeep N; Gelderman, Monique P; Lewis, Emily M A; Farrel, John; Wood, Francine; Strader, Michael Brad; Alayash, Abdu I; Vostal, Jaroslav G

    2016-01-01

    Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

  7. Benzylglucosinolate Derived Isothiocyanate from Tropaeolum majus Reduces Gluconeogenic Gene and Protein Expression in Human Cells.

    Directory of Open Access Journals (Sweden)

    Valentina Guzmán-Pérez

    Full Text Available Nasturtium (Tropaeolum majus L. contains high concentrations of benzylglcosinolate. We found that a hydrolysis product of benzyl glucosinolate-the benzyl isothiocyanate (BITC-modulates the intracellular localization of the transcription factor Forkhead box O 1 (FOXO1. FoxO transcription factors can antagonize insulin effects and trigger a variety of cellular processes involved in tumor suppression, longevity, development and metabolism. The current study evaluated the ability of BITC-extracted as intact glucosinolate from nasturtium and hydrolyzed with myrosinase-to modulate i the insulin-signaling pathway, ii the intracellular localization of FOXO1 and, iii the expression of proteins involved in gluconeogenesis, antioxidant response and detoxification. Stably transfected human osteosarcoma cells (U-2 OS with constitutive expression of FOXO1 protein labeled with GFP (green fluorescent protein were used to evaluate the effect of BITC on FOXO1. Human hepatoma HepG2 cell cultures were selected to evaluate the effect on gluconeogenic, antioxidant and detoxification genes and protein expression. BITC reduced the phosphorylation of protein kinase B (AKT/PKB and FOXO1; promoted FOXO1 translocation from cytoplasm into the nucleus antagonizing the insulin effect; was able to down-regulate the gene and protein expression of gluconeogenic enzymes; and induced the gene expression of antioxidant and detoxification enzymes. Knockdown analyses with specific siRNAs showed that the expression of gluconeogenic genes was dependent on nuclear factor (erythroid derived-like2 (NRF2 and independent of FOXO1, AKT and NAD-dependent deacetylase sirtuin-1 (SIRT1. The current study provides evidence that BITC might have a role in type 2 diabetes T2D by reducing hepatic glucose production and increasing antioxidant resistance.

  8. 3,3'-Diaryl-BINOL phosphoric acids as enantioselective extractants of benzylic primary amines.

    Science.gov (United States)

    Verkuijl, Bastiaan J V; de Vries, Johannes G; Feringa, Ben L

    2011-01-01

    We report that 3,3'-diaryl-BINOL phosphoric acids are effective enantioselective extractants in chiral separation methods based on reactive liquid-liquid extraction. These new extractants are capable of separating racemic benzylic primary amine substrates. The effect of the nature of the substituents at the 3,3'-positions of the host were examined as well as the structure of the substrate, together with important parameters such as the organic solvent, the pH of the aqueous phase, and the host stoichiometry. Titration of the substrate with the host was monitored by FTIR, NMR, UV-Vis, and CD spectroscopy, which provided insight into the structure of the host-guest complex involved in extraction. Copyright © 2010 Wiley-Liss, Inc.

  9. Electrocarboxylation of benzyl chlorides at silver cathode at the preparative scale level

    Energy Technology Data Exchange (ETDEWEB)

    Scialdone, Onofrio [Dipartimento di Ingegneria Chimica dei Processi e dei Materiali, Universita di Palermo, Viale delle Scienze, 90128 Palermo (Italy)], E-mail: scialdone@dicpm.unipa.it; Galia, Alessandro; Errante, Giuseppina [Dipartimento di Ingegneria Chimica dei Processi e dei Materiali, Universita di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Isse, Abdirisak Ahmed; Gennaro, Armando [Dipartimento di Scienze Chimiche, Universita di Padova, Via Marzolo 1, 35131 Padova (Italy); Filardo, Giuseppe [Dipartimento di Ingegneria Chimica dei Processi e dei Materiali, Universita di Palermo, Viale delle Scienze, 90128 Palermo (Italy)

    2008-01-01

    The electrocarboxylation of benzyl chlorides to the corresponding carboxylic acids performed at silver cathodes was investigated both theoretically and experimentally in order to find the influence of the operative parameters on the selectivity and on the Faradic efficiency of the process. Theoretical considerations were confirmed by the electrocarboxylation of 1-phenyl-1-chloroethane performed in undivided cells equipped with sacrificial anodes both in a bench-scale electrochemical batch reactor and in a continuous batch recirculation reaction system equipped with a parallel plate electrochemical cell. Selectivity and Faradic yields higher than 80% and 70%, respectively, were obtained by working under anhydrous conditions both under amperostatic and potentiostatic alimentation at appropriate values of either current density or applied potential.

  10. Electroluminescent properties of an electrochemically cross-linkable carbazole peripheral poly(benzyl ether) dendrimer.

    Science.gov (United States)

    Park, Jin Young; Kim, Dong-Eun; Ponnapati, Ramakrishna; Kim, Jong-Min; Kwon, Young-Soo; Advincula, Rigoberto C

    2011-04-04

    The electroluminescent (EL) properties of a cross-linkable carbazole-terminated poly(benzyl ether) dendrimer, G(3)-cbz DN, doped into a PVK:PBD host matrix with a double-layer device configuration are investigated. Different concentrations of the guest material can control device efficiency, related to chromaticity of white emission and the origin of excited-state complexes occurring between hole-transporting carbazole units (PVK or G(3)-cbz DN) and electron-transporting oxadiazole (PBD). Two excited states (exciplex and electroplex) generated at the interfaces of PVK/G(3)-cbz DN and PBD result in competitive emission, exhibiting a broad band in the EL spectra. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Benzyl Alcohol-Mediated Versatile Method to Fabricate Nonstoichiometric Metal Oxide Nanostructures.

    Science.gov (United States)

    Qamar, Mohammad; Adam, Alaaldin; Azad, Abdul-Majeed; Kim, Yong-Wah

    2017-11-22

    Nanostructured metal oxides with cationic or anionic deficiency find applications in a wide range of technological areas including the energy sector and environment. However, a facile route to prepare such materials in bulk with acceptable reproducibility is still lacking; many synthesis techniques are still only bench-top and cannot be easily scaled-up. Here, we report that the benzyl alcohol (BA)-mediated method is capable of producing a host of nanostructured metal oxides (MO x , where M = Ti, Zn, Ce, Sn, In, Ga, or Fe) with inherent nonstoichiometry. It employs multifunctional BA as a solvent, a reducing agent, and a structure-directing agent. Depending on the oxidation states of metal, elemental or nonstoichiometric oxide forms are obtained. Augmented photoelectrochemical oxidation of water under visible light by some of these nonstoichiometric oxides highlights the versatility of the BA-mediated synthesis protocol.

  12. Synthesis of 2,3-diyne-1,4-naphthoquinone derivatives and evaluation of cytotoxic activity against tumor cell lines

    International Nuclear Information System (INIS)

    Silva, Mauro G.; Camara, Celso A.; Silva, Tania M.S.; Feitosa, Anderson C.S.; Meira, Assuero S.; Pessoa, Claudia

    2013-01-01

    A series of 2,3-diyne-1,4-naphthoquinone derivatives was synthesized from 2,3-dibromo- 1,4-naphthoquinone and various functionalized terminal alkynes using palladium-catalyzed Sonogashira cross-coupling reaction. The diynes were evaluated as potential cytotoxic agents against three tumor cell lines: human ovarian adenocarcinoma (OVCAR-8), human metastatic prostate cancer (PC-3M) and human bronchoalveolar lung carcinoma (NCI-H358M), presenting, in general, satisfactory results for inhibition of cell growth. (author)

  13. Synthesis of 2,3-diyne-1,4-naphthoquinone derivatives and evaluation of cytotoxic activity against tumor cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Mauro G.; Camara, Celso A.; Silva, Tania M.S., E-mail: ccelso@dcm.ufrpe.br [Universidade Federal Rural de Pernambuco (LSCB/UFRPE), Recife, PE (Brazil). Dept. de Ciencias Moleculares. Lab. de Sintese de Compostos Bioativos; Feitosa, Anderson C.S.; Meira, Assuero S.; Pessoa, Claudia [Universidade Federal do Ceara (LOE/UFC), Fortaleza, CE (Brazil). Dept. de Fisiologia e Farmacologia. Lab. de Oncologia Experimental

    2013-09-15

    A series of 2,3-diyne-1,4-naphthoquinone derivatives was synthesized from 2,3-dibromo- 1,4-naphthoquinone and various functionalized terminal alkynes using palladium-catalyzed Sonogashira cross-coupling reaction. The diynes were evaluated as potential cytotoxic agents against three tumor cell lines: human ovarian adenocarcinoma (OVCAR-8), human metastatic prostate cancer (PC-3M) and human bronchoalveolar lung carcinoma (NCI-H358M), presenting, in general, satisfactory results for inhibition of cell growth. (author)

  14. Improved synthesis and application of [(11) C]benzyl iodide in positron emission tomography radiotracer production.

    Science.gov (United States)

    Pekošak, Aleksandra; Filp, Ulrike; Rotteveel, Lonneke; Poot, Alex J; Windhorst, Albert D

    2015-06-30

    Positron emission tomography has increased the demand for new carbon-11 radiolabeled tracers and building blocks. A promising radiolabeling synthon is [(11) C]benzyl iodide ([(11) C]BnI), because the benzyl group is a widely present functionality in biologically active compounds. Unfortunately, synthesis of [(11) C]BnI has received little attention, resulting in limited application. Therefore, we investigated the synthesis in order to significantly improve, automate, and apply it for labeling of the dopamine D2 antagonist [(11) C]clebopride as a proof of concept. [(11) C]BnI was synthesized from [(11) C]CO2 via a Grignard reaction and purified prior the reaction with desbenzyl clebopride. According to a one-pot procedure, [(11) C]BnI was synthesized in 11 min from [(11) C]CO2 with high yield, purity, and specific activity, 52 ± 3% (end of the cyclotron bombardment), 95 ± 3%, and 123 ± 17 GBq/µmol (end of the synthesis), respectively. Changes in the [(11) C]BnI synthesis are reduced amounts of reagents, a lower temperature in the Grignard reaction, and the introduction of a solid-phase intermediate purification. [(11) C]Clebopride was synthesized within 28 min from [(11) C]CO2 in an isolated decay-corrected yield of 11 ± 3% (end of the cyclotron bombardment) with a purity of >98% and specific activity (SA) of 54 ± 4 GBq/µmol (n = 3) at the end of the synthesis. Conversion of [(11) C]BnI to product was 82 ± 11%. The reliable synthesis of [(11) C]BnI allows the broad application of this synthon in positron emission tomography radiopharmaceutical development. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Modeling the Interest Rate Term Structure: Derivatives Contracts Dynamics and Evaluation

    Directory of Open Access Journals (Sweden)

    Pedro L. Valls Pereira

    2005-06-01

    Full Text Available This article deals with a model for the term structure of interest rates and the valuation of derivative contracts directly dependent on it. The work is of a theoretical nature and deals, exclusively, with continuous time models, making ample use of stochastic calculus results and presents original contributions that we consider relevant to the development of the fixed income market modeling. We develop a new multifactorial model of the term structure of interest rates. The model is based on the decomposition of the yield curve into the factors level, slope, curvature, and the treatment of their collective dynamics. We show that this model may be applied to serve various objectives: analysis of bond price dynamics, valuation of derivative contracts and also market risk management and formulation of operational strategies which is presented in another article.

  16. NEW SEMISYNTHETIC DERIVATIVES OF A BENZYLISOTHIOCYANATE ISOLATED FROM Moringa oleifera AND EVALUATION OF THEIR CYTOTOXIC ACTIVITY

    Directory of Open Access Journals (Sweden)

    Diana Kelly C. de Almeida

    Full Text Available From the natural product 4-(4'-O-acetyl-α-L-rhamnosyloxybenzylisothiocyanate (1, isolated from the flowers of Moringa oleifera Lam (Moringaceae, four new semisynthetic derivatives, N-[4-(4'-O-acetyl-α-L-rhamnosyloxybenzyl]-2-(pyridinil-4-carbonilhydrazine-1-carbothioamide (3, 4-(4'-O-acetyl-2',3'-dimesyloxy-α-L-rhamnosyloxybenzylisothiocyanate (4, N-[(4'-O-acetyl-α-L-rhamnosyloxybenzyl]hydrazinecarbothioamide (5, 4-[4'-O-acetyl-2',3'-O-bis(decanoiloxy-α-L-rhamnosyloxy]benzylisothiocianate (6, and the known compound 4-(2',3',4'-O-triacetyl-α-L-rhamnosyloxybenzylisothiocyanate (2, were obtained. All compounds were tested for their cytotoxicity against the tumor cell lines SF-295, HL-60, HCT-116 e PC-3. The natural product 1 and the semisynthetic derivatives 2 and 4 were the most active compounds (IC50 from16.0 to 3.7 µmol L-1 against all tumor cell lines.

  17. Evaluation of some non-toxic thiadiazole derivatives as bronze corrosion inhibitors in aqueous solution

    International Nuclear Information System (INIS)

    Varvara, Simona; Muresan, Liana Maria; Rahmouni, Kamal; Takenouti, Hisasi

    2008-01-01

    The inhibiting effect of four innoxious thiadiazole derivatives (2-mercapto-5-amino-1,3,4-thiadiazole (MAT), 2-mercapto-5-acetylamino-1,3,4-thiadiazole (MAcAT), 2-mercapto-5-methyl-1,3,4-thiadiazole (MMeT) and 2-mercapto-5-phenylamino-1,3,4-thiadiazole (MPhAT)) on bronze corrosion in an aerated solution of 0.2 g L -1 Na 2 SO 4 + 0.2 g L -1 NaHCO 3 at pH 5 was studied by potentiodynamic voltammetry and electrochemical impedance spectroscopy. The corrosion parameters determined from the polarisation curves indicate that the addition of the investigated thiadiazole derivatives decreases both cathodic and anodic current densities, due to an inhibition of the corrosion process, through the adsorption of thiadiazoles on the bronze surface. The inhibiting effect of the investigated organic compounds appears to be more pronounced on the anodic process than on the cathodic one and, except for the case MPhAT, it is enhanced by the increases of the inhibitors' concentration. The adsorption of the thiadiazole derivatives on bronze was confirmed by the presence of the nitrogen atoms in the EDX spectra of the bronze exposed to inhibitor-containing solutions. The magnitude of polarisation resistance values and, consequently, the inhibition efficiencies are influenced by the molecular structure of thiadiazole derivatives. The strongest inhibition was noticed in the presence of compounds with phenyl amino- or amino-functionalities in their molecules. The maximum protection efficiencies were obtained by addition of: 5 mM MAT (95.9%), 1 mM MAcAT (95.7%), 5 mM MMeT (92.6%) and 0.1 mM MPhAT (97%). EIS measurements also revealed that the inhibitor effectiveness of the optimal concentrations of thiadiazole is time-dependent

  18. Evaluation of some non-toxic thiadiazole derivatives as bronze corrosion inhibitors in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Varvara, Simona [Department of Topography, ' 1 Decembrie 1918' University, 11-13 Nicolae Iorga Street, 510009 Alba Iulia (Romania); Muresan, Liana Maria [Department of Physical Chemistry, ' Babes-Bolyai' University, 11 Arany-Janos Street, 400028 Cluj-Napoca (Romania)], E-mail: limur@chem.ubbcluj.ro; Rahmouni, Kamal; Takenouti, Hisasi [UPMC LISE - UPR 15 of the CNRS, ' Pierre and Marie Curie' University, Paris (France)

    2008-09-15

    The inhibiting effect of four innoxious thiadiazole derivatives (2-mercapto-5-amino-1,3,4-thiadiazole (MAT), 2-mercapto-5-acetylamino-1,3,4-thiadiazole (MAcAT), 2-mercapto-5-methyl-1,3,4-thiadiazole (MMeT) and 2-mercapto-5-phenylamino-1,3,4-thiadiazole (MPhAT)) on bronze corrosion in an aerated solution of 0.2 g L{sup -1} Na{sub 2}SO{sub 4} + 0.2 g L{sup -1} NaHCO{sub 3} at pH 5 was studied by potentiodynamic voltammetry and electrochemical impedance spectroscopy. The corrosion parameters determined from the polarisation curves indicate that the addition of the investigated thiadiazole derivatives decreases both cathodic and anodic current densities, due to an inhibition of the corrosion process, through the adsorption of thiadiazoles on the bronze surface. The inhibiting effect of the investigated organic compounds appears to be more pronounced on the anodic process than on the cathodic one and, except for the case MPhAT, it is enhanced by the increases of the inhibitors' concentration. The adsorption of the thiadiazole derivatives on bronze was confirmed by the presence of the nitrogen atoms in the EDX spectra of the bronze exposed to inhibitor-containing solutions. The magnitude of polarisation resistance values and, consequently, the inhibition efficiencies are influenced by the molecular structure of thiadiazole derivatives. The strongest inhibition was noticed in the presence of compounds with phenyl amino- or amino-functionalities in their molecules. The maximum protection efficiencies were obtained by addition of: 5 mM MAT (95.9%), 1 mM MAcAT (95.7%), 5 mM MMeT (92.6%) and 0.1 mM MPhAT (97%). EIS measurements also revealed that the inhibitor effectiveness of the optimal concentrations of thiadiazole is time-dependent.

  19. Synthesis and in vitro Evaluation of 2-heteroarylidene-1-tetralone Derivatives as Monoamine Oxidase Inhibitors.

    Science.gov (United States)

    Amakali, Klaudia T; Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2018-05-14

    The present study investigates the human monoamine oxidase (MAO) inhibition properties of a series of twelve 2-heteroarylidene-1-tetralone derivatives. Also included are related cyclohexylmethylidene, cyclopentylmethylidene and benzylidene substituted 1-tetralones. These compounds are related to the 2-benzylidene-1-indanone class of compounds which has previously been shown to inhibit the MAOs, with specificity for the MAO-B isoform. The target compounds were synthesised by the Claisen-Schmidt condensation between 7-methoxy-1-tetralone or 1-tetralone, and various aldehydes, under acid (hydrochloric acid) or base (potassium hydroxide) catalysis. The results of the MAO inhibition studies showed that the 2-heteroarylidene-1-tetralone and related derivatives are in most instances more selective inhibitors of the MAO-B isoform compared to MAO-A. (2E)-2-Benzylidene-7-methoxy-3,4-dihydronaphthalen-1(2 H)-one (IC 50 =0.707 μM) was found to be the most potent MAO-B inhibitor, while the most potent MAO-A inhibitor was (2E)-2-[(2-chloropyridin-3-yl)methylidene]-7-methoxy-3,4-dihydronaphthalen-1(2 H)-one (IC 50 =1.37 μM). The effect of the heteroaromatic substituent on MAO-B inhibition activity, in decreasing order was found to be: cyclohexyl, phenyl>thiophene>pyridine, furane, pyrrole, cyclopentyl. This study concludes that, although some 2-heteroarylidene-1-tetralone derivatives are good potency MAO inhibitors, in general their inhibition potencies, particularly for MAO-B, are lower than structurally related chalcones and 1-indanone derivatives that were previously studied. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Synthesis of novel kavain-like derivatives and evaluation of their cytotoxic activity

    Energy Technology Data Exchange (ETDEWEB)

    Amaral, Patricia de A.; Agustini, Taciane; Eifler-Lima, Vera L. [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (Brazil). Faculdade de Farmacia. Lab. de Sintese Organica Medicinal; Petrignet, Julien; Cariou, Alexandre; Gree, Rene [Universite de Rennes 1, Rennes (France). Lab. de Chimie Therapeutique; Gouault, Nicolas; Lohezic-Ledevehat, Francoise; David, Michele [CNRS UMR, Universite de Rennes 1, Rennes (France). Lab. de Chimie et Photonique Moleculaires

    2009-07-01

    Palladium-catalyzed cross coupling reactions (Sonogashira-Hagihara, Suzuki-Miyaura, and Heck) coupling and nickel hydride-mediated tandem isomerization aldolisation have been used for the synthesis of three series of {delta}-valerolactones substituted in positions 3, 4, 5 and 6 of the lactone ring. The 26 kavaien-like derivatives were tested against three cell lines and five of them exhibited a weak cytotoxic activity. (author)

  1. Comparative in vivo evaluation of two novel 99mTc labelled bombesin derivatives

    International Nuclear Information System (INIS)

    Gourni, Eleni; Bouziotis, Penelope; Zikos, Christos; Loudos, George; Xanthopoulos, Stavros; Fani, Melpomeni; Archimandritis, Spyridon C.; Varvarigou, Alexandra D.

    2006-01-01

    Bombesin (BN), a 14 amino acid peptide, is an analogue of human gastrin-releasing-peptide (GRP) that binds to GRP receptors (GRP-R) with high affinity and specificity. In addition to this physiological role, GRP, through its interaction with GRP-R, promotes tumour growth in a number of human cancer cell lines. The GRP receptors are over-expressed on a variety of human cancer cells. Aim of the present work is the study of two novels BN-like peptides, by investigating the radiochemical and radiopharmacological behaviour of their complexes with metals. The derivatives under study are: Gly-Gly-Cys-Aca-BN [2-14] where Aca: 6-amino-hexanoic acid. Pyroglutamic acid in the bombesin molecule has been replaced by the chemical group Gly-Gly-Cys-Aca, which bears an amino-acid combination capable of complexing a variety of radiometals. The other derivative under study is: Gly-Gly-Cys-Aca-BN [7-14]. This moiety of the peptide has been chosen because it has been proven to be a potent GRP agonist. The peptide derivatives were synthesized by SPPS, according to the Fmoc strategy and were identified by reverse phase high performance liquid chromatography (RP-HPLC). Radiolabelling with 99m Tc was performed via the precursor 99m Tc-gluconate. The stability of the radiolabelled species was examined with time. In vivo studies of the two 99m Tc-labelled derivatives were performed, comparatively, in normal mice, attention being focused on GRP receptor-bearing organs, and in experimentally induced prostate cancer models. Experimental tumours were imaged in a small field-of-view animal gamma camera

  2. Design, synthesis of novel chitosan derivatives bearing quaternary phosphonium salts and evaluation of antifungal activity.

    Science.gov (United States)

    Tan, Wenqiang; Zhang, Jingjing; Luan, Fang; Wei, Lijie; Chen, Yuan; Dong, Fang; Li, Qing; Guo, Zhanyong

    2017-09-01

    Two novel chitosan derivatives modified with quaternary phosphonium salts were successfully synthesized, including tricyclohexylphosphonium acetyl chitosan chloride (TCPACSC) and triphenylphosphonium acetyl chitosan chloride (TPPACSC), and characterized by FTIR, 1 H NMR, and 13 C NMR spectra. The degree of substitution was also calculated by elemental analysis results. Their antifungal activities against Colletotrichum lagenarium, Watermelon fusarium, and Fusarium oxysporum were investigated in vitro using the radial growth assay, minimal inhibitory concentration, and minimum bactericidal concentration assay. The fungicidal assessment revealed that the synthesized chitosan derivatives had superior antifungal activity compared with chitosan. Especially, TPPACSC exhibited the best antifungal property with inhibitory indices of over 75% at 1.0mg/mL. The results obviously showed that quaternary phosphonium groups could effectively enhance antifungal activity of the synthesized chitosan derivatives. Meanwhile, it was also found that their antifungal activity was influenced by electron-withdrawing ability of the quaternary phosphonium salts. The synthetic strategy described here could be utilized for the development of chitosan as antifungal biomaterials. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Evaluation of landslide susceptibility mapping techniques using lidar-derived conditioning factors (Oregon case study

    Directory of Open Access Journals (Sweden)

    Rubini Mahalingam

    2016-11-01

    Full Text Available Landslides are a significant geohazard, which frequently result in significant human, infrastructure, and economic losses. Landslide susceptibility mapping using GIS and remote sensing can help communities prepare for these damaging events. Current mapping efforts utilize a wide variety of techniques and consider multiple factors. Unfortunately, each study is relatively independent of others in the applied technique and factors considered, resulting in inconsistencies. Further, input data quality often varies in terms of source, data collection, and generation, leading to uncertainty. This paper investigates if lidar-derived data-sets (slope, slope roughness, terrain roughness, stream power index, and compound topographic index can be used for predictive mapping without other landslide conditioning factors. This paper also assesses the differences in landslide susceptibility mapping using several, widely used statistical techniques. Landslide susceptibility maps were produced from the aforementioned lidar-derived data-sets for a small study area in Oregon using six representative statistical techniques. Most notably, results show that only a few factors were necessary to produce satisfactory maps with high predictive capability (area under the curve >0.7. The sole use of lidar digital elevation models and their derivatives can be used for landslide mapping using most statistical techniques without requiring additional detailed data-sets that are often difficult to obtain or of lower quality.

  4. Evaluating Online CPD Using Educational Criteria Derived from the Experiential Learning Cycle.

    Science.gov (United States)

    Friedman, Andrew; Watts, David; Croston, Judith; Durkin, Catherine

    2002-01-01

    Develops a set of educational evaluation criteria for online continuing professional development (CPD) courses using Kolb's experiential learning cycle theory. Evaluates five courses provided by online CPD Web sites, concludes that these online courses neglect parts of the learning cycle, and suggests improvements. (Author/LRW)

  5. A new symmetry-based scoring method for posture assessment: evaluation of the effect of insoles with mineral derivatives.

    Science.gov (United States)

    Masse, M; Gaillardetz, C; Cron, C; Abribat, T

    2000-01-01

    There is a need for a validated rapid procedure for the evaluation of posture, defined as lateral balance/imbalance at the pelvic, shoulder, and neck levels. This would enable clinicians to determine the importance of symmetry in the pathophysiology of musculoskeletal disorders and to assess the efficacy of devices and treatments claiming to normalize or improve posture. In this investigation, the efficacy of such a device, a set of insoles with a hypothesized proprioceptive-like action, was evaluated through use of the described procedure. To develop a new scoring system to evaluate body posture on the basis of symmetry and to use this scoring system to investigate the efficacy of insoles containing a combination of mineral derivatives designed to balance posture through a neurophysiological effect. The posture score was based on the evaluation of 4 postural parameters: pelvic and shoulder lateral balance/imbalance, static shoulder rotation, and amplitude of head rotation. In the placebo-controlled study, 32 patients were tested in a double-blind fashion, either with placebo insoles or with insoles containing mineral derivatives. The same study was repeated in unblind conditions in 137 patients selected from 2 chiropractic clinics in an open-label protocol. A crossover placebo-controlled, double-blind study and a multicenter, large-scale, open-label study in patients selected from chiropractic clinics. A basal postural evaluation in 137 patients revealed that no patient had a perfect symmetry-ie, a perfectly or nearly perfectly balanced posture. The insoles with mineral derivatives induced a highly significant and similar improvement in the postural score in both the crossover double-blind study (32 patients; 56.7% improvement) and the open-label study (137 patients; 60.7% improvement, P postural imbalances according to the newly developed scoring method, and this method was successful in assessing the efficacy of insoles exerting a profound and immediate postural

  6. Novel Application of Stem Cell-Derived Neurons to Evaluate the Time-and Dose-Dependent Progression of Excitotoxic Injury

    Science.gov (United States)

    2013-05-14

    3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Novel Application of Stem Cell -Derived Neurons to Evaluate the Time- and Dose-Dependent 5a...01.10.RC.021). 14. ABSTRACT See reprint. 15. SUBJECT TERMS Mouse stem cell -derived neurons, NMDA receptor, AMPA receptor, Neurotoxicity, Apoptosis...area code) 410-436-8044 Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Novel Application of Stem Cell -Derived Neurons to Evaluate the

  7. Evaluation of hematopoietic potential generated by transplantation of muscle-derived stem cells in mice.

    Science.gov (United States)

    Farace, Francoise; Prestoz, Laetitita; Badaoui, Sabrina; Guillier, Martine; Haond, Celine; Opolon, Paule; Thomas, Jean-Leon; Zalc, Bernard; Vainchenker, William; Turhan, Ali G

    2004-02-01

    Muscle tissue of adult mice has been shown to contain stem cells with hematopoietic repopulation ability in vivo. To determine the functional characteristics of stem cells giving rise to this hematopoietic activity, we have performed hematopoietic reconstitution experiments by the use of muscle versus marrow transplantation in lethally irradiated mice and followed the fate of transplanted cells by Y-chimerism using PCR and fluorescence in situ hybridization (FISH) analysis. We report here that transplantation of murine muscle generate a major hematopoietic chimerism at the level of CFU-C, CFU-S, and terminally-differentiated cells in three generations of lethally irradiated mice followed up to 1 year after transplantation. This potential is totally abolished when muscle grafts were performed by the use of muscle from previously irradiated mice. As compared to marrow transplantation, muscle transplants were able to generate similar potencies to give rise to myeloid, T, B, and natural killer (NK) cells. Interestingly, marrow stem cells that have been generated in primary and then in secondary recipients were able to contribute efficiently to myofibers in the muscle tissue of tertiary recipients. Altogether, our data demonstrate that muscle-derived stem cells present a major hematopoietic repopulating ability with evidence of self-replication in vivo. They are radiation-sensitive and similar to marrow-derived stem cells in terms of their ability to generate multilineage hematopoiesis. Finally, our data demonstrate that muscle-derived hematopoietic stem cells do not lose their ability to contribute to myofiber generation after at least two rounds of serial transplantation, suggesting a potential that is probably equivalent to that generated by marrow transplantation.

  8. Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy

    Directory of Open Access Journals (Sweden)

    Claudia Wing

    2017-07-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin, taxanes (paclitaxel, docetaxel and nab-paclitaxel, a targeted proteasome inhibitor (bortezomib, an antiangiogenic compound (thalidomide, and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy. We demonstrate differential sensitivity of neurons to mechanistically distinct classes of chemotherapeutics. We also show a dose-dependent reduction of electrical activity as measured by mean firing rate of the neurons following treatment with paclitaxel. We compared neurite outgrowth and cell viability of iPSC-derived cortical (iCell® Neurons and peripheral (Peri.4U neurons to cisplatin, paclitaxel and vincristine. Goshajinkigan, a Japanese herbal neuroprotectant medicine, was protective against paclitaxel-induced neurotoxicity but not oxaliplatin as measured by morphological phenotypes. Thus, we have demonstrated the utility of human iPSC-derived neurons as a useful model to distinguish drug class differences and for studies of a potential neuroprotectant for the prevention of chemotherapy-induced peripheral neuropathy.

  9. Evaluation of ferrolysis in arsenate adsorption on the paddy soil derived from an Oxisol.

    Science.gov (United States)

    Jiang, Jun; Dai, Zhaoxia; Sun, Rui; Zhao, Zhenjie; Dong, Ying; Hong, Zhineng; Xu, Renkou

    2017-07-01

    Iron oxides are dominant effective adsorbents for arsenate in iron oxide-rich variable charge soils. Oxisol-derived paddy soils undergo intensive ferrolysis, which results in high leaching and transformation of iron oxides. However, little information is available concerning the effect of ferrolysis on arsenate adsorption by paddy soil and parent Oxisol. In the present study, we examined the arsenate affinity of soils using arsenate adsorption/desorption isotherms, zeta potential, adsorption kinetics, pH effect and phosphate competition experiments. Results showed that ferrolysis in an alternating flooding-drying Oxisol-derived paddy soil resulted in a significant decrease of free iron oxides and increase of amorphous iron oxides in the surface and subsurface layers. There were more reactive sites exposed on amorphous than on crystalline iron oxides. Therefore, disproportionate ratios of arsenate adsorption capacities and contents of free iron oxides were observed in the studied Oxisols compared with paddy soils. The Gibbs free energy values corroborated that both electrostatic and non-electrostatic adsorption mechanisms contributed to the arsenate adsorption by bulk soils, and the kinetic adsorption data further suggested that the rate-limiting step was chemisorption. The zeta potential of soil colloids decreased after arsenate was adsorbed on the surfaces, forming inner-sphere complexes and thus transferring their negative charges to the soil particle surfaces. The adsorption/desorption isotherms showed that non-electrostatic adsorption was the main mechanism responsible for arsenate binding to the Oxisol and derived paddy soils, representing 91.42-94.65% of the adsorption capacities. Further studies revealed that arsenate adsorption was greatly inhibited by increasing suspension pH and incorporation of phosphate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Synthesis and evaluation of the plant growth regulator property of indolic compounds derived from safrole

    International Nuclear Information System (INIS)

    Marchi, Irineu; Rebelo, Ricardo Andrade; Rosa, Flavia A. Fernandes da; Maiochi, Riceli A.

    2007-01-01

    The present work describes the use of piperonal, a derivative of the secondary metabolite safrole, for the synthesis of new 5,6-methylenedioxy substituted indole carboxylic acids structurally related to the indol-3-yl-acetic acid (AIA, I). The route comprises six steps beginning with piperonal with an overall yield of 19%. Compound IX was tested towards its plant growth regulator properties in bioassays specific for auxine activity. The in vitro assays were performed in a germination chamber and were of two types: root growth in germinated seeds of Lactuca sativa, Cucumbis sativus and Raphanus sativus and peciole biotest using Phaseolus vulgaris. (author)

  11. An evaluation of the physiological activity of 9-amine-9-fluorenephosphonic acid derivatives

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    Henryk Skrabka

    2013-12-01

    Full Text Available The physiological activity of eleven 9-amine-9-fluorenephosphonic acid derivatives, synthesized at the Wrocław Polytechnic, was examined. The test plant was Spirodela oligorrhiza. The effect of these compounds on the increase of the dry matter of this plant was tested in eight-day experiments. The activity of the compounds was varied. The most toxic were nos. 2, 4, 9, 8, 5 and 6 which were lethal in low concentrations. Somewhat less toxic were nos. 7, 10 and 11; nos. 1 and 3 were the least toxic.

  12. Synthesis and cytotoxic evaluation of novel C-10 nitrate derivatives of colchicine

    International Nuclear Information System (INIS)

    Shen, L.H.; Wang, B.; Liu, S.M.

    2016-01-01

    In our continuing search for more potent anticancer agent, eight novel nitrates couple with C-10 colchicine nitric oxide-releasing derivatives (5a-f and 7a-b) were prepared. These target compounds were assayed for their anti-tumor activity in vitro against four cancer cell lines, including human hepatocellular carcinoma cells (BEL7402), human ovary carcinoma cells (A2780), human lung adenocarcinoma cells (A549) and human breast carcinoma cells (MCF7). Preliminary results indicated that most of them exhibited significant cytotoxic effect toward cancer cells. Compound 7a was investigated further for its more potent cytotoxicity than colchicine. (author)

  13. Synthesis, pharmacological activity evaluation and molecular modeling of new polynuclear heterocyclic compounds containing benzimidazole derivatives.

    Science.gov (United States)

    Bassyouni, Fatma A; Saleh, Tamer S; ElHefnawi, Mahmoud M; Abd El-Moez, Sherein I; El-Senousy, Waled M; Abdel-Rehim, Mohamed E

    2012-12-01

    Novel heterocyclic compounds containing benzimidazole derivatives were synthesized from 2-(1H-benzimidazol-2-yl) acetonitrile (1) and arylhydrazononitrile derivative 2 was obtained via coupling of 1 with 4-methyl phenyldiazonium salt, which was then reacted with hydroxylamine hydrochloride to give amidooxime derivative 3. This product was cyclized into the corresponding oxadiazole derivative 4 upon reflux in acetic anhydride. Compound 4 was refluxed in DMF in the presence of triethylamine to give the corresponding 5-(1H-benzimidazol-2-yl)-2-p-tolyl-2H-1,2,3-triazol-4-amine 6. Treatment of compound 6 with ethyl chloroformate afforded 2,6-dihydro-2-(4-methylphenyl)-1,2,3-triazolo[4",5"-4',5']pyrimido[1,6-a]benzimidazole-5(4H)-one (8). 1,2-bis(2-cyanomethyl-1H-benzimidazol-1-yl)ethane-1,2-dione (10) was synthesized via the condensation reaction of 2-(1H-benzimidazol-2-yl) acetonitrile (1) and diethyloxalate. The reactivity of compound 10 towards some diamine reagents was studied. The in vitro antimicrobial activity of the synthesized compounds was investigated against several pathogenic bacterial strains such as Escherichia coli O157, Salmonella typhimurium, E. coli O119, S. paratyphi, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus. The results of MIC revealed that compounds 12a-c showed the most effective antimicrobial activity against tested strains. On the other hand, compounds 12a, b exhibited high activity against rotavirus Wa strain while compounds 12b, c exhibited high activity against adenovirus type 7. In silico target prediction, docking and validation of the compounds 12a-c were performed. The dialkylglycine decarboxylase bacterial enzyme was predicted as a potential bacterial target receptor using pharmacophore-based correspondence with previous leads; giving the highest normalized scores and a high correlation docking score with mean inhibition concentrations. A novel binding mechanism was predicted after docking

  14. Synthesis and antimalarial evaluation of some 4-quinazolinone derivatives based on febrifugine

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    Debanjan Sen

    2010-01-01

    Full Text Available A series of 2-substituted and 2,3-substituted quinazolin -4(3H-one derivatives were designed and synthesized based on the structure of febrifugine. The structures of the new compounds were confirmed by spectral analysis. The in vivo biological activity test results indicated that those compounds exhibited antimalarial activities against Plasmodium berghei in mice, at a dose of 5 mg/kg. Compared to Chloroquine and Artemisinin, these compounds have the advantages of shorter synthetic routes and consequently are highly cost effective in nature.

  15. Antibacterial evaluation of some Schiff bases derived from 2-acetylpyridine and their metal complexes.

    Science.gov (United States)

    Gwaram, Nura Suleiman; Ali, Hapipah Mohd; Khaledi, Hamid; Abdulla, Mahmood Ameen; Hadi, A Hamid A; Lin, Thong Kwai; Ching, Chai Lay; Ooi, Cher Lin

    2012-05-18

    A series of Schiff bases derived from 2-acetylpyridne and their metal complexes were characterized by elemental analysis, NMR, FT-IR and UV-Vis spectral studies. The complexes were screened for anti-bacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumanni (AC), Klebsiella pneumonie (KB) and Pseudomonas aeruginosa (PA) using the disc diffusion and micro broth dilution assays. Based on the overall results, the complexes showed the highest activities against MRSA while a weak antibacterial activity was observed against A. baumanii and P. aeruginosa.

  16. Biological evaluation and simple method for the synthesis of tetrahydrobenzo[a]xanthenes-11-one derivatives

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    Ali Akbari

    2017-01-01

    Full Text Available A simple method for the synthesis of Tetrahydrobenzo[a]xanthenes-11-one derivatives in the presence of BF3.SiO2, and its antibacterial activity was assessed against Pseudomonas syringae, Xanthomonas citi and Pectobacterium carotovorum. The structure of the isolated compounds has been determined by means of 1H/13C NMR and FT-IR spectroscopy. The reactions were carried out in water at room temperature for 5 h. This method has some advantages such as good to excellent yield, mild reaction condition, ease of operation and workup, high product purity and green process.

  17. Preparation and evaluation of some benzimidazole derivatives as antioxidants for local base oil

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    J.S. Basta

    2017-12-01

    Full Text Available Some benzimidazole derivatives, 2(1-H benzo(dimidazole-2-y1thio N-butyl acetamide Ia, 2(I-H benzo(dimidazole-2-ylthio N-octylacetamid Ib and 2(I-H benzo(dimidazole-2-yl thio N-dodecylactamide Ic were prepared and studied as antioxidants for base stock. The structure of these compounds was elucidated by elemental analysis, IR and 1H NMR spectroscopy. The inhibition efficiency of the prepared compounds was determined by studying the oxidation stability of the local base oil via the change in total acid number (TAN, viscosity and infrared (IR spectroscopy.

  18. Major questions about derivation of variance-covariance information for nuclear data evaluations

    International Nuclear Information System (INIS)

    Peelle, R.W.

    1982-01-01

    The uncertainties in and correlations among some evaluated nuclear data are now evaluated to permit estimation of data-related uncertainties in the outputs of neutronic calculations and to focus data improvement efforts. Questions are discussed that arise in trying to obtain adequate numerical files of variance-covariance uncertainty information. These involve (1) discrepant data, (2) experimental data with incompletely reported uncertainties, (3) uncertainties in nuclear model results, (4) uncertainty data for the resonance regions and for angle and energy distributions, and (5) the role of integral data in nuclear data evaluation. The question also arises whether files of uncertainty data designed for technological applications can suffice to represent past knowledge in an evaluation that includes new data. Directions are indicated toward resolving these questions

  19. In Silico Discovery of Novel Potent Antioxidants on the Basis of Pulvinic Acid and Coumarine Derivatives and Their Experimental Evaluation.

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    Rok Martinčič

    Full Text Available A pigment from the edible mushroom Xerocomus badius norbadione A, which is a natural derivative of pulvinic acid, was found to possess antioxidant properties. Since the pulvinic acid represents a novel antioxidant scaffold, several other derivatives were recently synthetized and evaluated experimentally, along with some structurally related coumarine derivatives. The obtained data formed the basis for the construction of several quantitative structure-activity and pharmacophore models, which were employed in the virtual screening experiments of compound libraries and for the prediction of their antioxidant activity, with the goal of discovering novel compounds possessing antioxidant properties. A final prioritization list of 21 novel compounds alongside 8 established antioxidant compounds was created for their experimental evaluation, consisting of the DPPH assay, 2-deoxyribose assay, β-carotene bleaching assay and the cellular antioxidant activity assay. Ten novel compounds from the tetronic acid and barbituric acid chemical classes displayed promising antioxidant activity in at least one of the used assays, that is comparable to or even better than some standard antioxidants. Compounds 5, 7 and 9 displayed good activity in all the assays, and were furthermore effective preventers of oxidative stress in human peripheral blood mononuclear cells, which are promising features for the potential therapeutic use of such compounds.

  20. Synthesis and Biological Evaluation of 2H-Indazole Derivatives: Towards Antimicrobial and Anti-Inflammatory Dual Agents

    Directory of Open Access Journals (Sweden)

    Jaime Pérez-Villanueva

    2017-10-01

    Full Text Available Indazole is considered a very important scaffold in medicinal chemistry. It is commonly found in compounds with diverse biological activities, e.g., antimicrobial and anti-inflammatory agents. Considering that infectious diseases are associated to an inflammatory response, we designed a set of 2H-indazole derivatives by hybridization of cyclic systems commonly found in antimicrobial and anti-inflammatory compounds. The derivatives were synthesized and tested against selected intestinal and vaginal pathogens, including the protozoa Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis; the bacteria Escherichia coli and Salmonella enterica serovar Typhi; and the yeasts Candida albicans and Candida glabrata. Biological evaluations revealed that synthesized compounds have antiprotozoal activity and, in most cases, are more potent than the reference drug metronidazole, e.g., compound 18 is 12.8 times more active than metronidazole against G. intestinalis. Furthermore, two 2,3-diphenyl-2H-indazole derivatives (18 and 23 showed in vitro growth inhibition against Candida albicans and Candida glabrata. In addition to their antimicrobial activity, the anti-inflammatory potential for selected compounds was evaluated in silico and in vitro against human cyclooxygenase-2 (COX-2. The results showed that compounds 18, 21, 23, and 26 display in vitro inhibitory activity against COX-2, whereas docking calculations suggest a similar binding mode as compared to rofecoxib, the crystallographic reference.

  1. Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation

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    Eman M. Flefel

    2017-01-01

    Full Text Available 4-(2-(4-Halophenylhydrazinyl-6-phenylpyridazin-3(2H-ones 1a,b were prepared and treated with phosphorus oxychloride, phosphorus pentasulphide and ethyl chloroformate to give the corresponding chloropyridazine, pyridazinethione, oxazolopyridazine derivatives 2–4, respectively. Compound 2 reacted with hydrazine hydrate to afford hydrazinylpyridazine 7. The reaction of 4-(2-(4-chlorophenylhydrazinyl-3-hydrazinyl-6-phenylpyridazine (7 with acetic anhydride, p-chlorobenzaldehyde and carbon disulphide gave the corresponding pyridazinotriazine derivatives 8–10. On the other hand, 5-(4-chlorophenylamino-7-(3,5-dimethoxybenzylidene-3-phenyl-5H-pyridazino[3,4-b][1,4]thiazin-6(7H-one (11 was prepared directly from the reaction of compound 3 with chloroacetic acid in presence of p-chlorobenzaldehyde. Compound 11 reacted with nitrogen nucleophiles (hydroxylamine hydrochloride, hydrazine hydrate and active methylene group-containing reagents (malononitrile, ethyl cyanoacetate to afford the corresponding fused compounds 12–15, respectively. Pharmacological screening for antiviral activity against hepatitis A virus (HAV was performed for the new compounds. 4-(4-Chlorophenylamino-6-phenyl-1,2-dihydropyridazino[4,3-e][1,2,4]triazine-3(4H-thione (10 showed the highest effect against HAV.

  2. Radiosynthesis and in vitro evaluation of 99mTc(CO)3-labeled folic acid derivative

    International Nuclear Information System (INIS)

    Drishty Satpati; Archana Mukherjee; Meera Venkatesh; Sharmila Banerjee

    2011-01-01

    The over-expression of folate receptors in variety of neoplastic tissues makes radiolabeled folate conjugates potential agents for imaging and therapy of such cancers. With the aim of preparing an imaging agent for targeting folate receptors, folic acid has been conjugated with homocysteine for complexation with [ 99m Tc(CO) 3 (H 2 O) 3 ] + core. The radiolabeled complex of the homocysteine-folate could be obtained in >95% radiochemical yield as observed by HPLC. Stability of complex in saline was studied and challenge studies with histidine and cysteine revealed kinetic stability of the complex. Lipophilicity of the radiolabeled complex (log P) was found to be 0.45. In vitro uptake of 99m Tc(CO) 3 -labeled folic acid derivative was studied in KB cells and inhibition studies were carried out using 3 H-folic acid and cold homocysteine-folate conjugate. The in vitro studies indicated loss of binding affinity of the derivative towards folate receptors. (author)

  3. Metabolism and toxicological evaluation of the aromatic amide herbicide propanil and its derivatives

    International Nuclear Information System (INIS)

    McMillian, D.C.

    1989-01-01

    Since propanil is structurally similar to other carcinogenic arylamides, the potential chronic toxicity of propanil and its derivatives were examined in short-term assays for genotoxicity. Propanil, 3,4-dichloroaniline, and their N-oxidized derivatives were inactive in the Salmonella typhimurium reversion, Chinese hamster ovary/hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT), and rat hepatocyte/DNA repair assays. The metabolism of propanil and 3,4-dichloroaniline was subsequently examined in liver microsomes from males Sprague-Dawley rats to identify metabolites that may be involved in the acute toxicity of propanil. The major pathway of propanil metabolism was acylamidase-catalyzed hydrolysis to 3,4-dichloroaniline. Oxidized metabolites were isolated by high performance liquid chromatography, and identified as 2'-hydroxy-propanil and 6-hydroxy-propanil by comparison of their mass and nuclear magnetic resonance spectra to synthetic standards. Experiments were performed to determine if propanil exposure could be monitored by the analysis of hemoglobin binding. Administration of [ring-U- 14 C]propanil to rats increased methemoglobin formation in a dose-dependent manner. Concomitant with methemoglobin formation, dose-dependent covalent binding of radiolabeled propanil to hemoglobin was detected. HPLC analysis indicated that the hemoglobin adducts were sulfinic acid esters, and these data suggest that human exposure to propanil may be monitored by the analysis of propanil metabolites bound to hemoglobin

  4. A generalized form of the Bernoulli Trial collision scheme in DSMC: Derivation and evaluation

    Science.gov (United States)

    Roohi, Ehsan; Stefanov, Stefan; Shoja-Sani, Ahmad; Ejraei, Hossein

    2018-02-01

    The impetus of this research is to present a generalized Bernoulli Trial collision scheme in the context of the direct simulation Monte Carlo (DSMC) method. Previously, a subsequent of several collision schemes have been put forward, which were mathematically based on the Kac stochastic model. These include Bernoulli Trial (BT), Ballot Box (BB), Simplified Bernoulli Trial (SBT) and Intelligent Simplified Bernoulli Trial (ISBT) schemes. The number of considered pairs for a possible collision in the above-mentioned schemes varies between N (l) (N (l) - 1) / 2 in BT, 1 in BB, and (N (l) - 1) in SBT or ISBT, where N (l) is the instantaneous number of particles in the lth cell. Here, we derive a generalized form of the Bernoulli Trial collision scheme (GBT) where the number of selected pairs is any desired value smaller than (N (l) - 1), i.e., Nsel < (N (l) - 1), keeping the same the collision frequency and accuracy of the solution as the original SBT and BT models. We derive two distinct formulas for the GBT scheme, where both formula recover BB and SBT limits if Nsel is set as 1 and N (l) - 1, respectively, and provide accurate solutions for a wide set of test cases. The present generalization further improves the computational efficiency of the BT-based collision models compared to the standard no time counter (NTC) and nearest neighbor (NN) collision models.

  5. Evaluation of the expansion of umbilical cord blood derived from CD133+ cells on biocompatible microwells

    Directory of Open Access Journals (Sweden)

    Mina Soufizomorrod

    2016-05-01

    Full Text Available Background: Hematopoietic stem cell transplantation (HSCT is a therapeutic approach for treatment of hematological malignancies and incompatibility of Bone marrow. Umbilical cord blood (UCB has known as an alternative for hematopoietic stem/progenitor cells (HPSC in allogeneic transplantation. The low volume of collected samples is the main hindrance in application of HPSC derived from umbilical cord blood. So, ex vivo expansion of HPSCs is the useful approach to overcome this restriction. The goal of using this system is to produce appropriate amount of hematopoietic stem cells, which have the ability of transplantation and long term haematopoiesis. Material & Methods: In current study CD133+ cells were isolated from cord blood (CB. Isolated cells were seeded on microwells. Then expanded cells proliferation rate and ability in colony formation were assessed and finally were compared with 2 Dimensional (2D culture systems. Results: Our findings demonstrated that CD133+ cells derived from UCB which were cultivated on microwells had significantly higher rate of proliferation in compared with routine cell culture systems. Conclusion: In Current study, it was shown that CD133+ cells’ proliferations which were seeded on PDMS microwells coated with collagen significantly increased. We hope that 3 dimensional (3D microenvironment which mimics the 3D structure of bone marrow can solve the problem of using UCB as an alternative source of bone marrow.

  6. Synthesis and Biological Evaluation of 3-Benzylidene-4-chromanone Derivatives as Free Radical Scavengers and α-Glucosidase Inhibitors.

    Science.gov (United States)

    Takao, Koichi; Yamashita, Marimo; Yashiro, Aruki; Sugita, Yoshiaki

    2016-01-01

    A series of 3-benzylidene-4-chromanone derivatives (3-20) were synthesized and the structure-activity relationships for antioxidant and α-glucosidase inhibitory activities were evaluated. Among synthesized compounds, compounds 5, 13, 18, which contain catechol moiety, showed the potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (5: EC50 13 µM; 13: EC50 14 µM; 18: EC50 13 µM). The compounds 12, 14, 18 showed higher α-glucosidase inhibitory activity (12: IC50 15 µM; 14: IC50 25 µM; 18: IC50 28 µM). The compound 18 showed both of potent DPPH radical scavenging and α-glucosidase inhibitory activities. These data suggest that 3-benzylidene-4-chromanone derivatives, such as compound 18, may serve as the lead compound for the development of novel α-glucosidase inhibitors with antioxidant activity.

  7. [Design, synthesis and evaluation of bis-nicotine derivatives as inhibitors of cholinesterases and beta-amyloid aggregation].

    Science.gov (United States)

    Luo, Wen; Zhao, Yong-mei; Tian, Run-guo; Su, Ya-bin; Hong, Chen

    2013-11-01

    A novel series of bis-nicotine derivatives (3a-3i) were designed, synthesized and evaluated as bivalent anti-Alzheimer's disease agents. The pharmacological results indicated that compounds 3e-3i inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the micromolar range (IC50, 2.28-117.86 micromol x L(-1) for AChE and 1.67-125 micromol x L(-1) for BChE), which was at the same potency as rivastigmine. A Lineweaver-Burk plot and molecular modeling study showed that these derivatives targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds could significantly inhibit the self-induced Abeta aggregation with inhibition activity (11.85%-62.14%) at the concentration of 20 micromol x L(-1).

  8. Synthesis of novel 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds and their evaluation for tuberculostatic activity.

    Science.gov (United States)

    Gobis, Katarzyna; Foks, Henryk; Bojanowski, Krzysztof; Augustynowicz-Kopeć, Ewa; Napiórkowska, Agnieszka

    2012-01-01

    A series of novel 3-cyclohexylpropanoic acid derivatives and 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds (1-8) have been synthesized and evaluated for tuberculostatic activity. Compounds 1a, 1c, 1e and 1f bearing benzimidazole or benzimidazole-like systems showed the most potent tuberculostatic activity against Mycobacterium tuberculosis strains with MIC values ranging from 1.5 to 12.5μg/mL. More importantly 1a (6-chloro-2-(2-cyclohexylethyl)-4-nitro-1H-benzo[d]imidazole) and 1f (2-(2-cyclohexylethyl)-1H-imidazo[4,5-b]phenazine) appeared selective for M. tuberculosis as compared with eukaryotic cells (human fibroblasts), and other antimicrobial strains. These compounds may thus represent a novel, selective class of antitubercular agents. Additionally compound 1a stimulated type I collagen output by fibroblasts, in vitro. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. LAI, FAPAR and FCOVER products derived from AVHRR long time series: principles and evaluation

    Science.gov (United States)

    Verger, A.; Baret, F.; Weiss, M.; Lacaze, R.; Makhmara, H.; Pacholczyk, P.; Smets, B.; Kandasamy, S.; Vermote, E.

    2012-04-01

    Continuous and long term global monitoring of the terrestrial biosphere has draught an intense interest in the recent years in the context of climate and global change. Developing methodologies for generating historical data records from data collected with different satellite sensors over the past three decades by taking benefits from the improvements identified in the processing of the new generation sensors is a new central issue in remote sensing community. In this context, the Bio-geophysical Parameters (BioPar) service within Geoland2 project (http://www.geoland2.eu) aims at developing pre-operational infrastructures for providing global land products both in near real time and off-line mode with long time series. In this contribution, we describe the principles of the GEOLAND algorithm for generating long term datasets of three key biophysical variables, leaf area index (LAI), Fraction of Absorbed Photosynthetic Active Radiation (FAPAR) and cover fraction (FCOVER), that play a key role in several processes, including photosynthesis, respiration and transpiration. LAI, FAPAR and FCOVER are produced globally from AVHRR Long Term Data Record (LTDR) for the 1981-2000 period at 0.05° spatial resolution and 10 days temporal sampling frequency. The proposed algorithm aims to ensure robustness of the derived long time series and consistency with the ones developed in the recent years, and particularly with GEOLAND products derived from VEGETATION sensor. The approach is based on the capacity of neural networks to learn a particular biophysical product (GEOLAND) from reflectances from another sensor (AVHRR normalized reflectances in the red and near infrared bands). Outliers due to possible cloud contamination or residual atmospheric correction are iteratively eliminated. Prior information based on the climatology is used to get more robust estimates. A specific gap filing and smoothing procedure was applied to generate continuous and smooth time series of decadal

  10. Synthesis, radiosynthesis and biological evaluation of 1, 4-dihydroquinoline derivatives as new carriers for specific brain delivery

    International Nuclear Information System (INIS)

    Foucout, L.; Bohn, P.; Dupas, G.; Marsais, F.; Levacher, V.; Gourand, F.; Dhilly, M.; Barre, L.; Bohn, P.; Costentin, J.; Abbas, A.

    2009-01-01

    In spite of numerous reports dealing with the use of 1, 4-dihydro-pyridines as carriers to deliver biological active compounds to the brain, this chemical delivery system (CDS) suffers from poor stability of the 1, 4-dihydropyridine derivatives towards oxidation and hydration reactions seriously limiting further investigations in vivo. In an attempt to overcome these limitations, we report herein the first biological evaluation of more stable annellated NADH models in the quinoline series as relevant neuro-active drug-carrier candidates. The radiolabeled 1, 4-dihydroquinoline [ 11 C]1a was prepared to be subsequently peripherally injected in rats. The injected animals were sacrificed and brains were collected. The radioactivity measured in rat brain indicated a rapid penetration of the carrier [ 11 C]1a into the CNS. HPLC analysis of brain homogenates showed that oxidation of [ 11 C]1a into the corresponding quinolinium salt [ 11 C]4a was completed in less than 5 min. An in vivo evaluation in mice is also reported to illustrate the potential of such 1, 4-dihydroquinoline derivatives to transport a neuro-active drug in the CNS. For this purpose, g-aminobutyric acid (GABA), well known to poorly cross the brain blood barrier (BBB) was connected to this 1, 4-dihydroquinoline-type carrier. After i.p. injection of 1, 4-dihydroquinoline-GABA derivative 1b in mice, a significant alteration of locomotor activity (LMA) was observed presumably resulting from an enhancement of central GABAergic activity. These encouraging results give strong evidence for the capacity of carrier-GABA derivative 1b to cross the BBB and exert a pharmacological effect on the CNS. This study paves the way for further progress in designing new redox chemical delivery systems. (authors)

  11. Synthesis, radiosynthesis and biological evaluation of 1, 4-dihydroquinoline derivatives as new carriers for specific brain delivery

    Energy Technology Data Exchange (ETDEWEB)

    Foucout, L.; Bohn, P.; Dupas, G.; Marsais, F.; Levacher, V. [Laboratoire de Chimie Organique Fine et Heterocyclique, UMR 6014, IRCOF, CNRS, Universite et INSA de Rouen, B.P. 08 F-76131, Mont- Saint-Aignan Cedex (France); Gourand, F.; Dhilly, M.; Barre, L. [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, CEA/DSV/I2BM/CI-NAPS UMR6232, Universite de Caen Basse Normandie, Caen (France); Bohn, P.; Costentin, J. [Laboratoire de Neuropharmacologie Experimentale associe au CNRS, FRE-2735, Faculte de Medecine et de pharmacie, Universite de Rouen, F-76000 (France); Abbas, A. [Inserm-EPHE-Universite de Caen Basse-Normandie, Unite U923, GIP Cyceron, CHU Cote de Nacre, Caen (France)

    2009-07-01

    In spite of numerous reports dealing with the use of 1, 4-dihydro-pyridines as carriers to deliver biological active compounds to the brain, this chemical delivery system (CDS) suffers from poor stability of the 1, 4-dihydropyridine derivatives towards oxidation and hydration reactions seriously limiting further investigations in vivo. In an attempt to overcome these limitations, we report herein the first biological evaluation of more stable annellated NADH models in the quinoline series as relevant neuro-active drug-carrier candidates. The radiolabeled 1, 4-dihydroquinoline [{sup 11}C]1a was prepared to be subsequently peripherally injected in rats. The injected animals were sacrificed and brains were collected. The radioactivity measured in rat brain indicated a rapid penetration of the carrier [{sup 11}C]1a into the CNS. HPLC analysis of brain homogenates showed that oxidation of [{sup 11}C]1a into the corresponding quinolinium salt [{sup 11}C]4a was completed in less than 5 min. An in vivo evaluation in mice is also reported to illustrate the potential of such 1, 4-dihydroquinoline derivatives to transport a neuro-active drug in the CNS. For this purpose, g-aminobutyric acid (GABA), well known to poorly cross the brain blood barrier (BBB) was connected to this 1, 4-dihydroquinoline-type carrier. After i.p. injection of 1, 4-dihydroquinoline-GABA derivative 1b in mice, a significant alteration of locomotor activity (LMA) was observed presumably resulting from an enhancement of central GABAergic activity. These encouraging results give strong evidence for the capacity of carrier-GABA derivative 1b to cross the BBB and exert a pharmacological effect on the CNS. This study paves the way for further progress in designing new redox chemical delivery systems. (authors)

  12. Evaluating the Effects of Cytomegalovirus Glycoprotein B on the Maturation and Function of Monocyte-derived dendritic cells

    Directory of Open Access Journals (Sweden)

    Afsson shariat

    2015-11-01

    Full Text Available Background & Objectives: Interaction of cytomegalovirus glycoprotein B with toll-like receptors of dendritic cells leads to early signaling and innate immune responses. The aim of this study is to evaluate the effects of cytomegalovirus glycoprotein B on the maturation and function of monocyte-derived dendritic cells in treated groups in comparison with control groups. Materials & Methods: Blood samples were taken from 5 healthy volunteers. Following the generation of monocyte-derived dendritic cells on the fifth day of cell culture, half of the immature dendritic cells were treated with cytomegalovirus glycoprotein B, and the rest of them were induced to mature dendritic untreated cells and were used as the control group. The maturation and function of dendritic cells were evaluated in these two groups. Results: The gene expression level of toll-like receptor-4 significantly increased in the group treated with glycoprotein B (p < 0.05, whereas there were no significant differences in the expression rates of CD83, CD86, CD1a, and HLA-DR and the secretion of IL-23 from monocyte-derived dendritic cells between the treated groups and the controls. Conclusion: The increase in the gene expression of toll-like receptor-4 in monocyte-derived dendritic cells treated with cytomegalovirus glycoprotein B showed that cell contact is required to elicit cellular antiviral response and toll-like receptor activation. Thus, it is critical to recognize the viral and cellular determinants of the immune system in order to develop new therapeutic strategies against cytomegalovirus.

  13. Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

    Directory of Open Access Journals (Sweden)

    Sandeep N Shah

    Full Text Available Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

  14. Synthesis and Pharmacological Evaluation of Novel Benzenesulfonamide Derivatives as Potential Anticonvulsant Agents

    Directory of Open Access Journals (Sweden)

    Zhiming Wang

    2015-09-01

    Full Text Available A novel series of benzenesulfonamide derivatives containing 4-aminobenzenesul-fonamide and α-amides branched valproic acid or 2,2-dimethylcyclopropanecarboxylic acid moieties were synthesized and screened for their anticonvulsant activities in mice maximal electroshock seizure (MES and subcutaneous pentylenetetrazole (scPTZ test. The activity experimental study showed that 2,2-dipropyl-N1-(4-sulfamoylphenylmalonamide (18b had the lowest median effective dose (ED50 of 16.36 mg/kg in MES test, and 2,2-dimethyl-N-(4-sulfamoylphenylcyclopropane-1,1-dicarboxamide (12c had the lowest ED50 of 22.50 mg/kg in scPTZ test, which resulted in the protective indexe (PI of 24.8 and 20.4, respectively. These promising data suggest the new compounds have good potential as new class of anticonvulsant agents with high effectiveness and low toxicity for the treatment of epilepsy.

  15. Synthesis and Anti-inflammatory Evaluation of Novel Benzimidazole and Imidazopyridine Derivatives.

    Science.gov (United States)

    Chen, Gaozhi; Liu, Zhiguo; Zhang, Yali; Shan, Xiaoou; Jiang, Lili; Zhao, Yunjie; He, Wenfei; Feng, Zhiguo; Yang, Shulin; Liang, Guang

    2013-01-10

    Sepsis, an acute inflammatory disease, remains the most common cause of death in intensive care units. A series of benzimidazole and imidazopyridine derivatives were synthesized and screened for anti-inflammatory activities, and the imidazopyridine series showed excellent inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Compounds X10, X12, X13, X14, and X15 inhibited TNF-α and IL-6 release in a dose-dependent manner, and X12 showed no cytotoxicity in hepatic cells. Furthermore, X12 exhibited a significant protection against LPS-induced septic death in mouse models. Together, these data present a series of new imidazopyridines with potential therapeutic effects in acute inflammatory diseases.

  16. In vitro evaluation of cardiomyogenic differentiation of bone marrow derived mesenchymal stem cells (MSCs)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Hwan; Lee, Yong Jin; Kang, Joo Hyun [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2010-10-15

    Bone marrow derived mesenchymal stem cells (MSCs) are excellent candidate as therapeutic agent for cell therapy. MSCs can be expanded in vitro rapidly (more than 3-5 fold in a weeks), and maintained their stem cell properties for a long culture period. Recently, many investigators have suggested that MSCs have ability to differentiate into cardiomyocytes by given appropriate condition in vitro or in vivo. Although, MSCs may be useful cell therapeutic agents in heart disease, there are still exist major barriers to track their capacity to differentiate into functional cardiomyocytes. In our previous study, the transgenic mouse model expressing sodium iodide symporter (NIS) driven by {alpha}-myosin heavy chain ({alpha}-MHC) promoter was developed to image cardiomyocyte with {gamma}-camera and microPET in vivo. In this study, we investigate the monitoring availability of {alpha}-MHC driven NIS gene of MSCs from the transgenic mouse during cardiomyogenic differentiation in vitro

  17. Antibacterial Evaluation of Some Schiff Bases Derived from 2-Acetylpyridine and Their Metal Complexes

    Directory of Open Access Journals (Sweden)

    Thong Kwai Lin

    2012-05-01

    Full Text Available A series of Schiff bases derived from 2-acetylpyridne and their metal complexes were characterized by elemental analysis, NMR, FT-IR and UV-Vis spectral studies. The complexes were screened for anti-bacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA, Acinetobacter baumanni (AC, Klebsiella pneumonie (KB and Pseudomonas aeruginosa (PA using the disc diffusion and micro broth dilution assays. Based on the overall results, the complexes showed the highest activities against MRSA while a weak antibacterial activity was observed against A. baumanii and P. aeruginosa.

  18. Evaluation of bias associated with capture maps derived from nonlinear groundwater flow models

    Science.gov (United States)

    Nadler, Cara; Allander, Kip K.; Pohll, Greg; Morway, Eric D.; Naranjo, Ramon C.; Huntington, Justin

    2018-01-01

    The impact of groundwater withdrawal on surface water is a concern of water users and water managers, particularly in the arid western United States. Capture maps are useful tools to spatially assess the impact of groundwater pumping on water sources (e.g., streamflow depletion) and are being used more frequently for conjunctive management of surface water and groundwater. Capture maps have been derived using linear groundwater flow models and rely on the principle of superposition to demonstrate the effects of pumping in various locations on resources of interest. However, nonlinear models are often necessary to simulate head-dependent boundary conditions and unconfined aquifers. Capture maps developed using nonlinear models with the principle of superposition may over- or underestimate capture magnitude and spatial extent. This paper presents new methods for generating capture difference maps, which assess spatial effects of model nonlinearity on capture fraction sensitivity to pumping rate, and for calculating the bias associated with capture maps. The sensitivity of capture map bias to selected parameters related to model design and conceptualization for the arid western United States is explored. This study finds that the simulation of stream continuity, pumping rates, stream incision, well proximity to capture sources, aquifer hydraulic conductivity, and groundwater evapotranspiration extinction depth substantially affect capture map bias. Capture difference maps demonstrate that regions with large capture fraction differences are indicative of greater potential capture map bias. Understanding both spatial and temporal bias in capture maps derived from nonlinear groundwater flow models improves their utility and defensibility as conjunctive-use management tools.

  19. Evaluation of the toxicity data for peracetic acid in deriving occupational exposure limits: a minireview.

    Science.gov (United States)

    Pechacek, Nathan; Osorio, Magdalena; Caudill, Jeff; Peterson, Bridget

    2015-02-17

    Peracetic acid (PAA) is a peroxide-based chemistry that is highly reactive and can produce strong local effects upon direct contact with the eyes, skin and respiratory tract. Given its increasing prominence in industry, attention has focused on health hazards and associated risks for PAA in the workplace. Occupational exposure limits (OEL) are one means to mitigate risks associated with chemical hazards in the workplace. A mini-review of the toxicity data for PAA was conducted in order to determine if the data were sufficient to derive health-based OELs. The available data for PAA frequently come from unpublished studies that lack sufficient study details, suffer from gaps in available information and often follow unconventional testing methodology. Despite these limitations, animal and human data suggest sensory irritation as the most sensitive endpoint associated with inhalation of PAA. Rodent RD50 data (the concentration estimated to cause a 50% depression in respiratory rate) were selected as the critical studies in deriving OELs. Based on these data, a range of 0.36-0.51mg/m(3) (0.1-0.2ppm) was calculated for a time-weighted average (TWA), and 1.2-1.7mg/m(3) (0.4-0.5ppm) as a range for a short-term exposure limit (STEL). These ranges compare favorably to other published OELs for PAA. Considering the applicable health hazards for this chemistry, a joint TWA/STEL OEL approach for PAA is deemed the most appropriate in assessing workplace exposures to PAA, and the selection of specific values within these proposed ranges represents a risk management decision. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Field production and functional evaluation of chloroplast-derived interferon-alpha2b.

    Science.gov (United States)

    Arlen, Philip A; Falconer, Regina; Cherukumilli, Sri; Cole, Amy; Cole, Alexander M; Oishi, Karen K; Daniell, Henry

    2007-07-01

    Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-alpha2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-alpha2b for the treatment of hepatitis C infection is $26,000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-alpha2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-alpha2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-alpha2b had similar in vitro biological activity to commercially produced PEG-Introntrade mark when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-alpha2b were also seen in vivo. Chloroplast-derived IFN-alpha2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-alpha2b purified from chloroplast transgenic lines (cpIFN-alpha2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-alpha2b, transgene containment and biological activity akin to that of commercial preparations of IFN-alpha2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization.

  1. Field production and functional evaluation of chloroplast-derived interferon-α2b

    Science.gov (United States)

    Arlen, Philip A.; Falconer, Regina; Cherukumilli, Sri; Cole, Amy; Cole, Alexander M.; Oishi, Karen K.; Daniell, Henry

    2008-01-01

    Summary Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-α2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-α2b for the treatment of hepatitis C infection is $26 000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-α2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-α2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-α2b had similar in vitro biological activity to commercially produced PEG-Intron™ when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-α2b were also seen in vivo . Chloroplast-derived IFN-α2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-α2b purified from chloroplast transgenic lines (cpIFN-α2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-α2b, transgene containment and biological activity akin to that of commercial preparations of IFN-α2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization. PMID:17490449

  2. Evaluation of Pulsed Doppler-Versus Tissue Doppler-Derived Tei Index of Right and Left Ventricle in Fetuses

    Directory of Open Access Journals (Sweden)

    Hamid Amoozgar

    2011-12-01

    Full Text Available Background: The myocardial performance index (MPI, also known as the Tei index, was introduced by Tei et al. to evaluate cardiac function in adults with dilated cardiomyopathy. This index is defined as the sum of isovolumic contraction time (ICT and isovolumic relaxation time (IRT, divided by ejection time (ET. Objectives: To determine the correlation between pulsed Doppler (PD- and tissue Doppler imaging (TDI-derived Tei indices in fetuses. Patients and Methods: Right and left ventricle PD and TDI echocardiographic data were obtained from 59 fetuses (11 pregnant women who were positive for anti-SSA-Ro or anti-SSB-La antibodies, 18 women who were referred due to dysrhythmia, and 30 women who had normal clinical findings. Results: Mean fetal gestational age was 27 ± 6.4 weeks. Mean PD Tei index of the mitral and tricuspid valve was 0.58 ± 0.05 and 0.53 ± 0.08, respectively. Mean TDI indices for the mitral and tricuspid valve were 0.56 ± 0.09 and 0.55 ± 0.08, respectively. There were no significant differences between mitral and tricuspid PD- and TDI-derived Tei indices (P = 0.87, P= 0.21, but the Bland-Altman diagrams showed no fine agreement between the indices (the mean difference ± 1 standard deviation of the right ventricular PD- and TDI-derived Tei indices was 0.24 ± 0.02 and 0.29 ± 0.04 for the left ventricle. There were no significant differences in PD- and TDI-derived Tei indexes between groups of evaluated fetuses (Mitral valve: PD-Tei P=0.69, TDI-Tei P=0.49; Tricuspid valve: PD-Tei P=0.41, TDI-Tei P=0.36. Conclusions: Although the mean values of the two indices did not differ significantly, the TDI-derived and PD-derived Tei indices did not have fine agreement.

  3. Synthesis, characterization and evaluation of 1,3,5-triazine aminobenzoic acid derivatives for their antimicrobial activity.

    Science.gov (United States)

    Al-Zaydi, Khadijah M; Khalil, Hosam H; El-Faham, Ayman; Khattab, Sherine N

    2017-05-10

    Replacement of chloride ions in cyanuric chloride give several variants of 1,3,5-triazine derivatives which were investigated as biologically active small molecules. These compounds exhibit antimalarial, antimicrobial, anti-cancer and anti-viral activities, among other beneficial properties. On the other hand, treatment of bacterial infections remains a challenging therapeutic problem because of the emerging infectious diseases and the increasing number of multidrug-resistant microbial pathogens. As multidrug-resistant bacterial strains proliferate, the necessity for effective therapy has stimulated research into the design and synthesis of novel antimicrobial molecules. 1,3,5-Triazine 4-aminobenzoic acid derivatives were prepared by conventional method or by using microwave irradiation. Using microwave irradiation gave the desired products in less time, good yield and higher purity. Esterification of the 4-aminobenzoic acid moiety afforded methyl ester analogues. The s-triazine derivatives and their methyl ester analogues were fully characterized by FT-IR, NMR ( 1 H-NMR and 13 C-NMR), mass spectra and elemental analysis. All the synthesized compounds were evaluated for their antimicrobial activity. Some tested compounds showed promising activity against Staphylococcus aureus and Escherichia coli. Three series of mono-, di- and trisubstituted s-triazine derivatives and their methyl ester analogues were synthesized and fully characterized. All the synthesized compounds were evaluated for their antimicrobial activity. Compounds (10), (16), (25) and (30) have antimicrobial activity against S. aureus comparable to that of ampicillin, while the activity of compound (13) is about 50% of that of ampicillin. Compounds (13) and (14) have antimicrobial activity against E. coli comparable to that of ampicillin, while the activity of compounds (9-12) and (15) is about 50% of that of ampicillin. Furthermore, minimum inhibitory concentrations values for clinical isolates of

  4. Synthesis and antimicrobial evaluation of the new Isoxazole and Pyrazole derivatives

    International Nuclear Information System (INIS)

    Goda, F.E.; Maarouf, A.R.; El-Bendary, E.R.

    2003-01-01

    A series of 3-methyl-4-substituted (phenylazo) isoxazolin-5-ones(5a,b),pyrazolin-5-ones (6a-d)and pyrazolidin-3,5-diones(10a-c) have been synthesized and evaluated for their antimicrobial activities.The detailed synthesis , spectroscopic and biogical data are reported. (author)

  5. Access to the substituted benzyl-1,2,3-triazolyl hesperetin derivatives expressing antioxidant and anticancer effects

    Czech Academy of Sciences Publication Activity Database

    Mistry, B.; Patel, Rahul V.; Keum, Y.S.

    2017-01-01

    Roč. 10, č. 2 (2017), s. 157-166 ISSN 1878-5352 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : free-radical method * oxidative stress * hesperidin * prevention * diseases * Hesperidin * Hesperetin * Cycloaddition * Click chemistry * Anticancer * Antioxidant Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Oncology Impact factor: 4.553, year: 2016

  6. Synthesis and biological evaluation of pyrrolidine derivatives as novel and potent sodium channel blockers for the treatment of ischemic stroke.

    Science.gov (United States)

    Seki, Maki; Tsuruta, Osamu; Tatsumi, Ryo; Soejima, Aki

    2013-07-15

    A novel series of pyrrolidine derivatives as Na(+) channel blockers was synthesized and evaluated for their inhibitory effects on neuronal Na(+) channels. Structure-activity relationship (SAR) studies of a pyrrolidine analogue 2 led to the discovery of 5e as a potent Na(+) channel blocker with a low inhibitory action against human ether-a-go-go-related gene (hERG) channels. Compound 5e showed remarkably neuroprotective activity in a rat transient middle cerebral artery occlusion (MCAO) model, suggesting that 5e would act as a neuroprotectant for ischemic stroke. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Synthesis and antimalarial activity evaluation of 3-(3-(7-chloroquinolin-4-ylaminopropyl-1,3-thiazinan-4-one derivatives

    Directory of Open Access Journals (Sweden)

    Mukesh Kumar Kumawat

    2016-09-01

    Full Text Available Some novel derivatives of 3-(3-(7-chloroquinolin-4-ylaminopropyl-1,3-thiazinan-4-one were synthesized and characterized by their physical and spectral data. All the synthesized compounds were subsequently screened for in vitro antimalarial activity against chloroquine sensitive strain of Plasmodium falciparum (RKL-2 employing chloroquine as the reference drug. Most of the synthesized compounds exhibited mild to moderate susceptibilities towards the parasite in comparison to the standard. It was found that antimalarial activity of 3-(3-(7-chloroquinolin-4-ylaminopropyl-2-(4-bromophenyl-1,3-thiazinan-4-one was marginally superior than all the compounds evaluated.

  8. ynthesis and Characterization of 1-Aryl-5-hepta-O-acetyl-β-D-maltosyl-2-S-benzyl-2,4-isodithiobiurets

    Directory of Open Access Journals (Sweden)

    R. D. Ghuge

    2012-01-01

    Full Text Available The facile synthesis of 1-aryl-5-hepta-o-acetyl-β-D-maltosyl-2-S-benzyl-2,4-isodithiobiurets (IIIa-g has been achieved by the interaction of 1-hepta-O-acetyl-β–D-maltosyl isothiocyanate (I with various1-aryl-S-benzyl isothiocarbamides (IIa-g. All the newly synthesized N-maltosylated compounds characterized by elemental analysis, IR, NMR and Mass spectral studies.

  9. (1S,3S,4S-tert-Butyl N-[1-benzyl-3-hydroxy-5-phenyl-4-(picolinamidopentyl]carbamate

    Directory of Open Access Journals (Sweden)

    Jian-Feng Zheng

    2008-07-01

    Full Text Available The title compound, C29H35N3O4, was obtained by the reaction of (2S,4S,5S-tert-butyl N-(4-amino-1-benzyl-3-hydroxy-5-phenylpentylcarbamate and picolinic acid using oxalyl chloride as a chlorinating reagent to activate the carboxyl group. In the crystal structure there are two molecules in the asymmetric unit, which are aligned edge-to-face. In one molecule, the pyridyl ring forms a dihedral angle of 22.0 (1° with the phenyl ring of the terminal benzyl group and 14.3 (1° with the other phenyl ring; in the other molecule, the corresponding angles are 12.1 (1 and 10.6 (1°, respectively. The packing is stabilized by intermolecular hydrogen bonds and C—H...π interactions.

  10. Molecular origin of the selectivity differences between palladium and gold-palladium in benzyl alcohol oxidation: Different oxygen adsorption properties

    Energy Technology Data Exchange (ETDEWEB)

    Savara, Aditya Ashi [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Chan-Thaw, Carine E. [Univ. degli Studi di Milano, Milano (Italy); Sutton, Jonathan E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wang, Di [Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen (Germany); Prati, Laura [Univ. degli Studi di Milano, Milano (Italy); Villa, Alberto [Univ. degli Studi di Milano, Milano (Italy)

    2016-12-22

    The same mechanism and microkinetic model used for benzyl alcohol oxidation over Pd/C was shown to apply to benzyl alcohol oxidation over AuPd/C. Almost all of the selectivity differences could be explained by a decrease in oxygen adsorption on AuPd. After isolating oxygen adsorption as being the origin of the selectivity differences, density functional theory was used to investigate the oxygen adsorption properties of a pure Pd surface, a pure Au surface, and an alloyed AuPd surface. Finally, the calculations showed that Au–Pd alloying decreased the oxygen adsorption properties relative to pure Pd, which explained the selectivity differences, consistent with the microkinetic modeling.

  11. Pulvinic synthesis and evaluation of pulvinic derivatives like agents of protection against radiation ionising

    International Nuclear Information System (INIS)

    Heurtaux, Benoit

    2006-01-01

    This work is devoted to the by-products preparation of mushrooms pigments, the pulvinic acids then to the evaluation of their oxidizing properties in the aim to find new compounds susceptible to be employed as protective drugs against ionizing radiation. An efficient method of symmetric pulvinic acids has been finalized. It is based on a double condensation of silylated cetenes acetals with oxalyl chloride. The treatment of the products got by D.B.U. leads to esters of corresponding pulvinic acids that are then saponified. The oxidizing properties have been studied. Then, the interaction between the pulvinic by-products and DNA are studied. Finally, the evaluation of radioprotective properties of the different synthesized compounds on different models (bacteria, eucaryotes cell and animal) is presented. (N.C.)

  12. Isolation and evaluation of cytotoxic potential of phenolic derivatives from Schinus terebinthifolius Raddi (Anacardiaceae)

    International Nuclear Information System (INIS)

    Santana, Jeferson S.; Sartorelli, Patricia; Lago, Joao Henrique G.; Matsuo, Alisson L.

    2012-01-01

    The EtOH extract from leaves of S. terebinthifolius was subjected to partition between EtOH:H 2 O and hexane, CH 2 Cl 2 , and EtOAc. The phases obtained were evaluated in vitro against human tumoral cell lines and the EtOAc phase exhibited activity. Chromatographic procedures afforded gallic acid (1), methyl (2) and ethyl (3) gallates, trans-catechin (4), quercitrin (5), and afzelin (6), being the first occurrence of 1, 4 and 6 in S. terebinthifolius. In vitro cytotoxic evaluation of 1 - 6 indicated that gallic acid (1) displayed higher activity than ethyl gallate (3) against HL-60 and HeLa cells, while compounds 2, 4 - 6 were inactive. (author)

  13. Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors

    Directory of Open Access Journals (Sweden)

    Shuang Cao

    2016-07-01

    Full Text Available A novel series of PI3Kβ (Phosphatidylinositol-3-kinases beta subunit inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3Kα, β, γ, δ and mTOR (Mammalian target of rapamycin. Two superior compounds have been further evaluated for the IC50 values against PI3Ks/mTOR. The most promising compound 11 displays excellent anti-proliferative activity and selectivity in multiple cancer cell lines, especially in the prostate cancer cell line. Docking studies indicate the morpholine group in 2-position of benzothiazole is necessary for the potent antitumor activity, which confirms our design is reasonable.

  14. 2D evaluation of spectral LIBS data derived from heterogeneous materials using cluster algorithm

    Science.gov (United States)

    Gottlieb, C.; Millar, S.; Grothe, S.; Wilsch, G.

    2017-08-01

    Laser-induced Breakdown Spectroscopy (LIBS) is capable of providing spatially resolved element maps in regard to the chemical composition of the sample. The evaluation of heterogeneous materials is often a challenging task, especially in the case of phase boundaries. In order to determine information about a certain phase of a material, the need for a method that offers an objective evaluation is necessary. This paper will introduce a cluster algorithm in the case of heterogeneous building materials (concrete) to separate the spectral information of non-relevant aggregates and cement matrix. In civil engineering, the information about the quantitative ingress of harmful species like Cl-, Na+ and SO42- is of great interest in the evaluation of the remaining lifetime of structures (Millar et al., 2015; Wilsch et al., 2005). These species trigger different damage processes such as the alkali-silica reaction (ASR) or the chloride-induced corrosion of the reinforcement. Therefore, a discrimination between the different phases, mainly cement matrix and aggregates, is highly important (Weritz et al., 2006). For the 2D evaluation, the expectation-maximization-algorithm (EM algorithm; Ester and Sander, 2000) has been tested for the application presented in this work. The method has been introduced and different figures of merit have been presented according to recommendations given in Haddad et al. (2014). Advantages of this method will be highlighted. After phase separation, non-relevant information can be excluded and only the wanted phase displayed. Using a set of samples with known and unknown composition, the EM-clustering method has been validated regarding to Gustavo González and Ángeles Herrador (2007).

  15. Green synthesis of novel quinoline based imidazole derivatives and evaluation of their antimicrobial activity

    Directory of Open Access Journals (Sweden)

    N.C. Desai

    2014-12-01

    Full Text Available We have described the conventional and microwave method for the synthesis of N-(4-((2-chloroquinolin-3-ylmethylene-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl(arylamides 3a–l. It is observed that the solvent-free microwave thermolysis is a convenient, rapid, high-yielding, and environmental friendly protocol for the synthesis of quinoline based imidazole derivatives when compared with conventional reaction in a solution phase. Antimicrobial activity of the newly synthesized compounds is screened in vitro on the following microbial cultures: Escherichia coli (MTCC 443, Pseudomonas aeruginosa (MTCC 1688, Staphylococcus aureus (MTCC 96, Streptococcus pyogenes (MTCC 442, Candida albicans (MTCC 227, Aspergillus niger (MTCC 282, Aspergillus clavatus (MTCC 1323. All the synthesized bio-active molecules are tested for their in vitro antimicrobial activity by bioassay namely serial broth dilution. Among these compounds 3c, 3d, 3f, 3h and 3j show significant potency against different microbial strains. All the compounds have been characterized by IR, 1H NMR, 13C NMR and mass spectral data. On the basis of statistical analysis, it is observed that these compounds give significant co-relation.

  16. Synthesis of Azole-containing Piperazine Derivatives and Evaluation of their Antibacterial, Antifungal and Cytotoxic Activities

    International Nuclear Information System (INIS)

    Gan, Lin Ling; Fang, Bo; Zhou, Cheng He

    2010-01-01

    A series of azole-containing piperazine derivatives have been designed and synthesized. The obtained compounds were investigated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that most compounds exhibited moderate to significant antibacterial and antifungal activities in vitro. 1-(4-((4-chlorophenyl) (phenyl)methyl)piperazin-1-yl)-2-(1H-imidazol-1-yl)ethanone and 1-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1- yl)-2-(2-phenyl-1H-imidazol-1-yl)ethanone gave remarkable and broad-spectrum antimicrobial efficacy against all tested strains with MIC values ranging from 3.1 to 25 μg/mL, and exhibited comparable activities to the standard drugs chloramphenicol and fluconazole in clinic. Moreover, 2-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)- 1H-benzo[d]imidazole was found to be the most effective in vitro against the PC-3 cell line, reaching growth inhibition values (36.4, 60.1 and 76.5%) for each tested concentration: 25 μM, 50 μM and 100 μM in dose-dependent manner. The results also showed that the azole ring had noticeable effect on their antimicrobial and cytotoxic activities, and imidazole and benzimidazole moiety were much more favourable to biological activity than 1,2,4-triazole

  17. Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B.

    Science.gov (United States)

    Li, Xiang-Qian; Xu, Qi; Luo, Jiao; Wang, Li-Jun; Jiang, Bo; Zhang, Ren-Shuai; Shi, Da-Yong

    2017-08-18

    Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic target to effectively treat T2DM and obesity. However, the development of charged PTP1B inhibitors was restricted due to their low cell permeability and poor bioavailability. Based on active natural products, two series of uncharged catechol derivatives were identified as PTP1B inhibitors by targeting a secondary aryl phosphate-binding site as well as the catalytic site. The most potent inhibitor 22 showed an IC 50 of 0.487 μM against PTP1B and strong selectivity (27-fold) over TCPTP. Kinetic studies were also performed that 22 act as a competitive PTP1B inhibitor. The treatment of C2C12 myotubes with 22 markedly increased the phosphorylation levels of IRβ, Akt and IRS1 phosphorylation. The similarity of its action profiling with that produced by insulin suggested its potential as a new non-insulin-dependent drug candidate. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Evaluating Lignocellulosic Biomass, Its Derivatives, and Downstream Products with Raman Spectroscopy

    Science.gov (United States)

    Lupoi, Jason S.; Gjersing, Erica; Davis, Mark F.

    2015-01-01

    The creation of fuels, chemicals, and materials from plants can aid in replacing products fabricated from non-renewable energy sources. Before using biomass in downstream applications, it must be characterized to assess chemical traits, such as cellulose, lignin, or lignin monomer content, or the sugars released following an acid or enzymatic hydrolysis. The measurement of these traits allows researchers to gage the recalcitrance of the plants and develop efficient deconstruction strategies to maximize yields. Standard methods for assessing biomass phenotypes often have experimental protocols that limit their use for screening sizeable numbers of plant species. Raman spectroscopy, a non-destructive, non-invasive vibrational spectroscopy technique, is capable of providing qualitative, structural information and quantitative measurements. Applications of Raman spectroscopy have aided in alleviating the constraints of standard methods by coupling spectral data with multivariate analysis to construct models capable of predicting analytes. Hydrolysis and fermentation products, such as glucose and ethanol, can be quantified off-, at-, or on-line. Raman imaging has enabled researchers to develop a visual understanding of reactions, such as different pretreatment strategies, in real-time, while also providing integral chemical information. This review provides an overview of what Raman spectroscopy is, and how it has been applied to the analysis of whole lignocellulosic biomass, its derivatives, and downstream process monitoring. PMID:25941674

  19. Synthesis and functional evaluation of a peptide derivative of 1-beta-D-arabinofuranosylcytosine.

    Science.gov (United States)

    Balajthy, Z; Aradi, J; Kiss, I T; Elödi, P

    1992-09-04

    We have synthesized a peptidyl prodrug derivative of 1-beta-D-arabinofuranosylcytosine (1) designed to be a selective substrate of plasmin. D-Val-Leu-Lys-ara-C (2) was obtained by coupling the protected peptide Cbz-D-Val-Leu-(N6-Cbz)Lys-OH and ara-C (1) by a water-soluble carbodiimide (EDCI), followed by the removal of the Cbz groups by using catalytic hydrogenolysis over Pd/C. The kinetic constant of hydrolysis of 2 in the presence of plasmin demonstrated effective release of 1. The amino group of 1, which is sensitive to the removal by cytidine deaminase, is protected in 2 by the formation of the amide bond resulting in a prolonged half-life of 2 in biological milieu. The antiproliferative efficiency of 2 against L1210 leukemic cells was significantly higher than that of 1. The activity of 2 was abolished in the presence of serine proteinase inhibitor, (4-amidinopheny)methanesulfonyl fluoride. These data indicate that 2 is a prodrug form of 1 in systems generating plasmin.

  20. Evaluation of a Naturally-derived Deflocculant (Terminalia Chebula in Bentonite Dispersions

    Directory of Open Access Journals (Sweden)

    Jalal Neshat

    2016-04-01

    Full Text Available The unwanted addition of salt to drilling causes flocculation which has an adverse effect on mud rheological properties. To treat the flocculated mud chemical, deflocculants are commonly used; however, their disadvantages such as negative environmental effects, lower tolerance to contamination, and toxicity motivated scientists to search for effective additives. Using plant derived additives instead of commercial additives could help resolve the mentioned weaknesses, because they are nontoxic, cheap, easily accessible, and act multi-functional. In this paper the effect of black myrobalan rheological properties of flocculated bentonite mud was investigated and its performance was compared with chrome lignosulfonate (CLS. Rheological and filtration tests were conducted and properties such as plastic viscosity, yield point, gel strength, thixotropy, and apparent viscosity were calculated. It was perceived that by increasing black myrobalan concentration to 0.6 wt.%, rheological parameters and filtration loss decreased by 50% and 66.3% respectively, but they increased at higher concentrations, which indicated that black myrobalan acted as a deflocculant up to 0.6 wt.%. The deflocculation behavior of black myrobalan at low concentrations is attributed to ellagitannic acid and tannic acid. The comparison of the enactment of black myrobalan with chrome lignosulfonate showed that black myrobalan had a stronger decreasing effect on the rheological parameters and filtration compared to CLS.

  1. Preparation and biocompatibility evaluation of apatite/wollastonite-derived porous bioactive glass ceramic scaffolds

    International Nuclear Information System (INIS)

    Zhang Hua; Ye Xiaojian; Li Jiashun

    2009-01-01

    An apatite/wollastonite-derived (A/W) porous glass ceramic scaffold with highly interconnected pores was successfully fabricated by adding a plastic porosifier. The morphology, porosity and mechanical strength were characterized. The results showed that the glass ceramic scaffold with controllable pore size and porosity displayed open macropores. In addition, good in vitro bioactivity was found for the scaffold obtained by soaking it in simulated body fluid. Mesenchymal stem cells (MSCs) were cultured, expanded and seeded on the scaffold, and the adhesion and proliferation of MSCs were determined using MTT assay and environmental scanning electron microscopy (ESEM). The results revealed that the scaffold was biocompatible and had no negative effects on the MSCs in vitro. The in vivo biocompatibility and osteogenicity were investigated by implanting both the pure scaffold and the MSC/scaffold construct in rabbit mandibles and studying histologically. The results showed that the glass ceramic scaffold exhibited good biocompatibility and osteoconductivity. Moreover, the introduction of MSCs into the scaffold observably improved the efficiency of new bone formation, especially at the initial stage after implantation. However, the glass ceramic scaffold showed the same good biocompatibility and osteogenicity as the hybrid one at the later stage. These results indicate that porous bioactive scaffolds based on the original apatite-wollastonite glass ceramic fulfil the basic requirements of a bone tissue engineering scaffold.

  2. Design, Synthesis, Molecular Docking, and Antibacterial Evaluation of Some Novel Flouroquinolone Derivatives as Potent Antibacterial Agent

    Directory of Open Access Journals (Sweden)

    Mehul M. Patel

    2014-01-01

    Full Text Available Objective. Quinolone moiety is an important class of nitrogen containing heterocycles widely used as key building blocks for medicinal agents. It exhibits a wide spectrum of pharmacophores and has bactericidal, antiviral, antimalarial, and anticancer activities. In view of the reported antimicrobial activity of various fluoroquinolones, the importance of the C-7 substituents is that they exhibit potent antimicrobial activities. Our objective was to synthesize newer quinolone analogues with increasing bulk at C-7 position of the main 6-fluoroquinolone scaffold to produce the target compounds which have potent antimicrobial activity. Methods. A novel series of 1-ethyl-6-fluoro-4-oxo-7-{4-[2-(4-substituted phenyl-2-(substituted-ethyl]-1-piperazinyl}-1,4-dihydroquinoline-3-carboxylic acid derivatives were synthesized. To understand the interaction of binding sites with bacterial protein receptor, the docking study was performed using topoisomerase II DNA gyrase enzymes (PDB ID: 2XCT by Schrodinger’s Maestro program. In vitro antibacterial activity of the synthesized compounds was studied and the MIC value was calculated by the broth dilution method. Results. Among all the synthesized compounds, some compounds showed potent antimicrobial activity. The compound 8g exhibited good antibacterial activity. Conclusion. This investigation identified the potent antibacterial agents against certain infections.

  3. Synthesis and in Vitro Antiproliferative Evaluation of Some B-norcholesteryl Benzimidazole and Benzothiazole Derivatives

    Directory of Open Access Journals (Sweden)

    Jianguo Cui

    2015-04-01

    Full Text Available Taking orostanal (a compound from a Japanese marine sponge, Stelletta hiwasaensis as a lead compound, some novel B-norcholesteryl benzimidazole and benzothiazole derivatives were synthesized. The antiproliferative activity of the compounds against human cervical carcinoma (HeLa, human lung carcinoma (A549, human liver carcinoma cells (HEPG2 and normal kidney epithelial cells (HEK293T was assayed. The results revealed that the benzimidazole group was a better substituent than benzothiazole group for increasing the antiproliferative activity of compounds. 2-(3β′-Acetoxy-5β′-hydroxy-6′-B-norcholesterylbenzimidazole (9b with the structure of 6-benzimidazole displays the best antiproliferative activity to the cancer cells in all compounds, but is almost inactive to normal kidney epithelial cells (HEK293T. The assay of compound 9b to cancer cell apoptosis by flow cytometry showed that the compound was able to effectively induce cancer cell apoptosis. The research provided a theoretical reference for the exploration of new anti-cancer agents and may be useful for the design of novel chemotherapeutic drugs.

  4. Synthesis of Azole-containing Piperazine Derivatives and Evaluation of their Antibacterial, Antifungal and Cytotoxic Activities

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Lin Ling; Fang, Bo; Zhou, Cheng He [Southwest University, Chongqing (China)

    2010-12-15

    A series of azole-containing piperazine derivatives have been designed and synthesized. The obtained compounds were investigated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that most compounds exhibited moderate to significant antibacterial and antifungal activities in vitro. 1-(4-((4-chlorophenyl) (phenyl)methyl)piperazin-1-yl)-2-(1H-imidazol-1-yl)ethanone and 1-(4-((4-Chlorophenyl)(phenyl)methyl)piperazin-1- yl)-2-(2-phenyl-1H-imidazol-1-yl)ethanone gave remarkable and broad-spectrum antimicrobial efficacy against all tested strains with MIC values ranging from 3.1 to 25 μg/mL, and exhibited comparable activities to the standard drugs chloramphenicol and fluconazole in clinic. Moreover, 2-((4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)methyl)- 1H-benzo[d]imidazole was found to be the most effective in vitro against the PC-3 cell line, reaching growth inhibition values (36.4, 60.1 and 76.5%) for each tested concentration: 25 μM, 50 μM and 100 μM in dose-dependent manner. The results also showed that the azole ring had noticeable effect on their antimicrobial and cytotoxic activities, and imidazole and benzimidazole moiety were much more favourable to biological activity than 1,2,4-triazole.

  5. Re-evaluating neptunium in uranyl phases derived from corroded spent fuel

    International Nuclear Information System (INIS)

    Fortner, J. A.; Finch, R. J.; Kropf, A. J.; Cunnane, J. C.; Chemical Engineering

    2004-01-01

    Interest in mechanisms that may control radioelement release from corroded commercial spent nuclear fuel (CSNF) has been heightened by the selection of the Yucca Mountain site in Nevada as the repository for high-level nuclear waste in the United States. Neptunium is an important radionuclide in repository models owing to its relatively long half-life and its high aqueous mobility as neptunyl [Np(V)O+2]. The possibility of neptunium sequestration into uranyl alteration phases produced by corroding CSNF would suggest-a process for lowering neptunium concentration and subsequent migration from a geologic repository. However, there remains little experimental evidence that uranyl compounds will, in fact, serve as long-term host phases for the retention of neptunium under conditions expected in a deep geologic repository. To directly explore this possibility, we examined specimens of uranyl alteration phases derived from humid-air-corroded CSNF by X-ray absorption spectroscopy to better determine neptunium uptake in these phases. Although neptunium fluorescence was readily observed from as-received CSNF, it was not observed from the uranyl alteration rind. We establish upper limits for neptunium incorporation into CSNF alteration phases that are significantly below previously reported concentrations obtained by using electron energy loss spectroscopy (EELS). We attribute the discrepancy to a plural-scattering event that creates a spurious EELS peak at the neptunium-MV energy

  6. Substoichiometric extraction and quantification of cobalt with potassium salts of ethyl, propyl, butyl, pentyl and benzyl xanthates

    International Nuclear Information System (INIS)

    Chandrasekhar Reddy, P.; Rangamannar, B.; Prasad, K.S.S.

    1999-01-01

    A rapid and sensitive substoichiometric radiochemical procedure has been developed for the extraction of cobalt with potassium salts of ethyl, propyl, butyl, pentyl and benzyl xanthates. The relative extractabilities of the cobalt-xanthate complexes into chloroform and carbon tetrachloride were studied. Substoichiometric quantification methods were developed in each case and utilised to determine the cobalt content present in standard solutions as well as biological samples. (author)

  7. Evaluation of the antimicrobial activity of chitosan and its quaternized derivative on E. coli and S. aureus growth

    Directory of Open Access Journals (Sweden)

    Rejane C. Goy

    Full Text Available Abstract Chitosan is largely known for its activity against a wide range of microorganisms, in which the most acceptable antimicrobial mechanism is found to include the presence of charged groups in the polymer backbone and their ionic interactions with bacteria wall constituents. This interaction suggests the occurrence of a hydrolysis of the peptidoglycans in the microorganism wall, provoking the leakage of intracellular electrolytes, leading the microorganism to death. The charges present in chitosan chains are generated by protonation of amino groups when in acid medium or they may be introduced via structural modification. This latter can be achieved by a methylation reaction resulting in a quaternized derivative with a higher polymeric charge density. Since the charges in this derivative are permanents, it is expected a most efficient antimicrobial activity. Hence, in the present study, commercial chitosan underwent quaternization processes and both (mother polymer and derivative were evaluated, in gel form, against Staphylococcus aureus (Gram-positive and Escherichia coli (Gram-negative, as model bacteria. The results, as acquired from turbidity measurements, differ between materials with an expressive reduction on the Gram-positive microorganism (S. aureus growth, while E. coli (Gram-negative strain was less sensitive to both polymers. Additionally, the antibacterial effectiveness of chitosan was strongly dependent on the concentration, what is discussed in terms of spatial polymer conformation.

  8. Radiation cross-linking of ethylene vinyl alcohol copolymer functionalized with m-isopropenyl-α,α-dimethyl benzyl isocyanate

    International Nuclear Information System (INIS)

    Ekman, K.B.; Naesman, J.H.

    1993-01-01

    An ethylene vinyl alcohol copolymer was functionalized with m-isopropenyl-α,α-dimethyl benzyl isocyanate using reactive processing in a mixer. The functionalization introduces pendant unsaturation to the polymer, which allows radiation cross-linked to gel contents >70% at radiation doses below 100 kGy. Unfunctionalized ethylene vinyl alcohol copolymer, on the other hand, forms no gel upon irradiation. The functionalization was completed within a few minutes of reactive mixing, which was confirmed with both FTIR and 13 C-NMR measurements. The oxygen permeability of ethylene vinyl alcohol copolymer increased with increasing degree of functionalization, and irradiation of the samples formed trapped radicals, which act as oxygen scavengers. Consequently no oxygen permeability was detected. However, radical activity was inhibited by annealing the samples at 110 C resulting in a 24% higher oxygen permeability value for the irradiated unfunctionalized copolymer. The oxygen permeability values of the irradiated functionalized samples were approximately 13% lower. Laminates of m-isopropenyl-α,α-dimethyl benzyl isocyanate functionalized ethylene vinyl alcohol copolymer and m-isopropenyl-α,α-dimethyl benzyl isocyanate functionalized ethylene hydroxyethyl methacrylate copolymer acquired improved adhesive strength both at dry and wet conditions as well as at elevated temperature upon exposure to radiation

  9. Optimization of Microencapsulation Composition of Menthol, Vanillin, and Benzyl Acetate inside Polyvinyl Alcohol with Coacervation Method for Application in Perfumery

    Science.gov (United States)

    Sahlan, Muhamad; Raihani Rahman, Mohammad

    2017-07-01

    One of many applications of essential oils is as fragrance in perfumery. Menthol, benzyl acetate, and vanillin, each represents olfactive characteristic of peppermint leaves, jasmine flowers, and vanilla beans, are commonly used in perfumery. These components are highly volatile, hence the fragrance components will quickly evaporate resulting in short-lasting scent and low shelf life. In this research, said components have been successfully encapsulated simultaneously inside Polyvinyl Alcohol (PVA) using simple coacervation method to increase its shelf life. Optimization has been done using Central Composite Diagram with 4 independent variables, i.e. composition of menthol, benzyl acetate, vanillin, and tergitol 15-S-9 (as emulsifier). Encapsulation efficiency, loading capacity, and microcapsule size have been measured. In optimized composition of menthol (13.98 %w/w), benzyl acetate (14.75 %w/w), vanillin (17.84 %w/w), and tergitol 15-S-9 (13.4 %w/w) encapsulation efficiency of 97,34% and loading capacity of 46,46% have been achieved. Mean diameter of microcapsule is 20,24 μm and within range of 2,011-36,24 μm. Final product was achieved in the form of cross linked polyvinyl alcohol with hydrogel consistency and orange to yellow in color.

  10. A preliminary evaluation of a combined tire- and refuse-derived fuel (TDF-RDF)

    Energy Technology Data Exchange (ETDEWEB)

    Stessel, R.I.; Amari, T.; Themelis, N.J.; Wearnick, I.K.

    1999-07-01

    In dense urban areas of the US, it is now becoming clear that waste management is far from economically-optimum. Even with the popularity of inexpensive land disposal, hauling and recycling costs are driving up the average waste bill. An historic option has been refuse-derived fuel, or RDF. Difficulties included low energy content and difficulty obtaining uniformity. Today, many resource-recovery technologies used in RDF are finding their way into materials recovery facilities (MRFs), some of which are reviving the automated processing of waste. Any MRF, automated or not, will have residue streams. Currently, one of the most significant problems is waste tires. Local options are difficult to locate in dense urban areas. As fuels, tires typically have energy contents considerably above those for which most solid-fuel combustors are designed, leading to thermal imbalances and various forms of failure. This paper suggests a new fuel that can be either co-fired with coal, or used in its own right in a combustor primarily designed for coal: TDF-RDF. A preliminary examination is undertaken of thermal and emissions characteristics, and possible costs for a few applications of the fuel. Immediately, TDF is already cleaner-burning than many coals, even in sulfur emissions. RDF has been widely-regarded as being similarly cleanly. Posited MRF residue streams should be still cleaner, and more consistent, than RDF. Overall, there is quite a potential for developing a fuel that would allow old coal powerplants in historic urban centers to be better neighbors, while helping with a few problems in municipal waste management.

  11. Independent evaluation of the SNODAS snow depth product using regional scale LiDAR-derived measurements

    Science.gov (United States)

    Hedrick, A.; Marshall, H.-P.; Winstral, A.; Elder, K.; Yueh, S.; Cline, D.

    2014-06-01

    Repeated Light Detection and Ranging (LiDAR) surveys are quickly becoming the de facto method for measuring spatial variability of montane snowpacks at high resolution. This study examines the potential of a 750 km2 LiDAR-derived dataset of snow depths, collected during the 2007 northern Colorado Cold Lands Processes Experiment (CLPX-2), as a validation source for an operational hydrologic snow model. The SNOw Data Assimilation System (SNODAS) model framework, operated by the US National Weather Service, combines a physically-based energy-and-mass-balance snow model with satellite, airborne and automated ground-based observations to provide daily estimates of snowpack properties at nominally 1 km resolution over the coterminous United States. Independent validation data is scarce due to the assimilating nature of SNODAS, compelling the need for an independent validation dataset with substantial geographic coverage. Within twelve distinctive 500 m × 500 m study areas located throughout the survey swath, ground crews performed approximately 600 manual snow depth measurements during each of the CLPX-2 LiDAR acquisitions. This supplied a dataset for constraining the uncertainty of upscaled LiDAR estimates of snow depth at the 1 km SNODAS resolution, resulting in a root-mean-square difference of 13 cm. Upscaled LiDAR snow depths were then compared to the SNODAS-estimates over the entire study area for the dates of the LiDAR flights. The remotely-sensed snow depths provided a more spatially continuous comparison dataset and agreed more closely to the model estimates than that of the in situ measurements alone. Finally, the results revealed three distinct areas where the differences between LiDAR observations and SNODAS estimates were most drastic, suggesting natural processes specific to these regions as causal influences on model uncertainty.

  12. Independent evaluation of the SNODAS snow depth product using regional-scale lidar-derived measurements

    Science.gov (United States)

    Hedrick, A.; Marshall, H.-P.; Winstral, A.; Elder, K.; Yueh, S.; Cline, D.

    2015-01-01

    Repeated light detection and ranging (lidar) surveys are quickly becoming the de facto method for measuring spatial variability of montane snowpacks at high resolution. This study examines the potential of a 750 km2 lidar-derived data set of snow depths, collected during the 2007 northern Colorado Cold Lands Processes Experiment (CLPX-2), as a validation source for an operational hydrologic snow model. The SNOw Data Assimilation System (SNODAS) model framework, operated by the US National Weather Service, combines a physically based energy-and-mass-balance snow model with satellite, airborne and automated ground-based observations to provide daily estimates of snowpack properties at nominally 1 km resolution over the conterminous United States. Independent validation data are scarce due to the assimilating nature of SNODAS, compelling the need for an independent validation data set with substantial geographic coverage. Within 12 distinctive 500 × 500 m study areas located throughout the survey swath, ground crews performed approximately 600 manual snow depth measurements during each of the CLPX-2 lidar acquisitions. This supplied a data set for constraining the uncertainty of upscaled lidar estimates of snow depth at the 1 km SNODAS resolution, resulting in a root-mean-square difference of 13 cm. Upscaled lidar snow depths were then compared to the SNODAS estimates over the entire study area for the dates of the lidar flights. The remotely sensed snow depths provided a more spatially continuous comparison data set and agreed more closely to the model estimates than that of the in situ measurements alone. Finally, the results revealed three distinct areas where the differences between lidar observations and SNODAS estimates were most drastic, providing insight into the causal influences of natural processes on model uncertainty.

  13. Evaluation of the trading development in the Iberian Energy Derivatives Market

    International Nuclear Information System (INIS)

    Capitán Herráiz, Álvaro; Rodríguez Monroy, Carlos

    2012-01-01

    The efficiency of the Iberian Energy Derivatives Market in its first five and a half years is assessed in terms of volume, open interest and price. The continuous market shows steady liquidity growth. Its volume is strongly correlated to that of the Over The Counter (OTC) market, the amount of market makers, the enrolment of financial agents and generation companies belonging to the integrated group of last resort suppliers, and the OTC cleared volume in its clearing house. The hedging efficiency, measured through the ratio between the final open interest and the cleared volume, shows the lowest values for the Spanish base load futures as they are the most liquid contracts. The ex-post forward risk premium has diminished due to the learning curve and the effect of the fixed price retributing the indigenous coal fired generation. This market is quite less developed than the European leaders headquartered in Norway and Germany. Enrolment of more traders, mainly international energy companies, financial agents, energy intensive industries and renewable generation companies is desired. Market monitoring reports by the market operator providing post-trade transparency, OTC data access by the energy regulator, and assessment of the regulatory risk can contribute to efficiency gains. - Highlights: ► The continuous traded volumes in the Iberian power futures market grow steadily. ► Those volumes are correlated to OTC volumes and the enrolment of key players. ► Most liquid contracts show the smallest hedging ratio. ► Regulation fixing the coal fired generation price affects spot and forward prices. ► The overall efficiency can grow via market monitoring reports and OTC data access.

  14. Evaluation of geomagnetic storm effects on the GPS derived Total Electron Content (TEC)

    International Nuclear Information System (INIS)

    Purohit, P K; Atulkar, Roshni; Mansoori, Azad A; Khan, Parvaiz A; Bhawre, Purushottam; Tripathi, Sharad C; Khatarkar, Prakash; Bhardwaj, Shivangi; Aslam, A M; Waheed, Malik A; Gwal, A K

    2015-01-01

    The geomagnetic storm represents the most outstanding example of solar wind- magnetospheric interaction, which causes global disturbances in the geomagnetic field as well as triggers ionospheric disturbances. We study the behaviour of ionospheric Total Electron Content (TEC) during the geomagnetic storms. For this investigation we have selected 47 intense geomagnetic storms (Dst ≤ -100nT) that were observed during the solar cycle 23 i.e. during 1998- 2006. We then categorized these storms into four categories depending upon their solar sources like Magnetic Cloud (MC), Co-rotating Interaction Region (CIR), SH+ICME and SH+MC. We then studied the behaviour of ionospheric TEC at a mid latitude station Usuda (36.13N, 138.36E), Japan during these storm events produced by four different solar sources. During our study we found that the smooth variations in TEC are replaced by rapid fluctuations and the value of TEC is strongly enhanced during the time of these storms belonging to all the four categories. However, the greatest enhancements in TEC are produced during those geomagnetic storms which are either caused by Sheath driven Magnetic cloud (SH+MC) or Sheath driven ICME (SH+ICME). We also derived the correlation between the TEC enhancements produced during storms of each category with the minimum Dst. We found the strongest correlation exists for the SH+ICME category followed by SH+MC, MC and finally CIR. Since the most intense storms were either caused by SH+ICME or SH+MC while the least intense storms were caused by CIR, consequently the correlation was strongest with SH+ICME and SH+MC and least with CIR. (paper)

  15. In vitro evaluation of demineralized freeze-dried bone allograft in combination with enamel matrix derivative.

    Science.gov (United States)

    Miron, Richard J; Bosshardt, Dieter D; Laugisch, Oliver; Dard, Michel; Gemperli, Anja C; Buser, Daniel; Gruber, Reinhard; Sculean, Anton

    2013-11-01

    Preclinical and clinical studies suggest that a combination of enamel matrix derivative (EMD) with demineralized freeze-dried bone allograft (DFDBA) may improve periodontal wound healing and regeneration. To date, no single study has characterized the effects of this combination on in vitro cell behavior. The aim of this study is to test the ability of EMD to adsorb to the surface of DFDBA particles and determine the effect of EMD coating on downstream cellular pathways such as adhesion, proliferation, and differentiation of primary human osteoblasts and periodontal ligament (PDL) cells. DFDBA particles were precoated with EMD or human blood and analyzed for protein adsorption patterns via scanning electron microscopy. Cell attachment and proliferation were quantified using a commercial assay. Cell differentiation was analyzed using real-time polymerase chain reaction for genes encoding Runx2, alkaline phosphatase, osteocalcin, and collagen 1α1, and mineralization was assessed using alizarinred staining. Analysis of cell attachment revealed no significant differences among control, blood-coated, and EMD-coated DFDBA particles. EMD significantly increased cell proliferation at 3 and 5 days after seeding for both osteoblasts and PDL cells compared to control and blood-coated samples. Moreover, there were significantly higher messenger ribonucleic acid levels of osteogenic differentiation markers, including collagen 1α1, alkaline phosphatase, and osteocalcin, in osteoblasts and PDL cells cultured on EMD-coated DFDBA particles at 3, 7, and 14 days. The results suggest that the addition of EMD to DFDBA particles may influence periodontal regeneration by stimulating PDL cell and osteoblast proliferation and differentiation.

  16. Synthesis and biological evaluation of some novel 1-indanone thiazolylhydrazone derivatives as anti-Trypanosoma cruzi agents.

    Science.gov (United States)

    Caputto, María E; Ciccarelli, Alejandra; Frank, Fernanda; Moglioni, Albertina G; Moltrasio, Graciela Y; Vega, Daniel; Lombardo, Elisa; Finkielsztein, Liliana M

    2012-09-01

    A series of novel 4-arylthiazolylhydrazones (TZHs) derived from 1-indanones were synthesized in good yields (66-92%) in a simple procedure using microwave irradiation and then characterized by spectroscopy studies. The compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against the epimastigote, trypomastigote and amastigote forms of the parasite. Most TZHs displayed excellent activity, and were more potent and selective than the reference drug Benznidazole, used in the current chemotherapy. Analysis of the free sterols from parasite incubated with the compounds showed that inhibition of ergosterol biosynthesis is a possible target for the action of these new TZHs. In particular, TZH 9 emerged as a promising antichagasic compound to be evaluated in animal models. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  17. Evaluation of small area crop estimation techniques using LANDSAT- and ground-derived data. [South Dakota

    Science.gov (United States)

    Amis, M. L.; Martin, M. V.; Mcguire, W. G.; Shen, S. S. (Principal Investigator)

    1982-01-01

    Studies completed in fiscal year 1981 in support of the clustering/classification and preprocessing activities of the Domestic Crops and Land Cover project. The theme throughout the study was the improvement of subanalysis district (usually county level) crop hectarage estimates, as reflected in the following three objectives: (1) to evaluate the current U.S. Department of Agriculture Statistical Reporting Service regression approach to crop area estimation as applied to the problem of obtaining subanalysis district estimates; (2) to develop and test alternative approaches to subanalysis district estimation; and (3) to develop and test preprocessing techniques for use in improving subanalysis district estimates.

  18. Comments on derivation of an index for evaluating economics of cogeneration systems and its applications

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, R [Indian Inst. of Tech., Bombay (India). Dept. of Mechanical Engineering

    1990-04-01

    Industrial cogeneration systems usually must satisfy a power load and heat loads at different temperatures. The limitations of the economic index proposed by Pak and Suzuki for such cogeneration systems is discussed in this paper. The importance of a rational exergetic basis for evaluation of different grades of energy is emphasised. Thermodynamic criteria, e.g. the exergetic efficiency, relative fuel savings and fuel chargeable to power, are shown to provide useful information regarding cogeneration options. Any assessment scheme for cogeneration schemes must incorporate thermodynamic criteria in addition to economic criteria. (author).

  19. Theoretical Derivation of Simplified Evaluation Models for the First Peak of a Criticality Accident in Nuclear Fuel Solution

    International Nuclear Information System (INIS)

    Nomura, Yasushi

    2000-01-01

    In a reprocessing facility where nuclear fuel solutions are processed, one could observe a series of power peaks, with the highest peak right after a criticality accident. The criticality alarm system (CAS) is designed to detect the first power peak and warn workers near the reacting material by sounding alarms immediately. Consequently, exposure of the workers would be minimized by an immediate and effective evacuation. Therefore, in the design and installation of a CAS, it is necessary to estimate the magnitude of the first power peak and to set up the threshold point where the CAS initiates the alarm. Furthermore, it is necessary to estimate the level of potential exposure of workers in the case of accidents so as to decide the appropriateness of installing a CAS for a given compartment.A simplified evaluation model to estimate the minimum scale of the first power peak during a criticality accident is derived by theoretical considerations only for use in the design of a CAS to set up the threshold point triggering the alarm signal. Another simplified evaluation model is derived in the same way to estimate the maximum scale of the first power peak for use in judging the appropriateness for installing a CAS. Both models are shown to have adequate margin in predicting the minimum and maximum scale of criticality accidents by comparing their results with French CRiticality occurring ACcidentally (CRAC) experimental data

  20. Evaluation of wound healing treated with latex derived from rubber trees and Aloe Vera extract in rats.

    Science.gov (United States)

    Brandão, Marcelo Luiz; Reis, Paulo Roberto Melo; Araújo, Lilhian Alves de; Araújo, Ana Carolina Vicente; Santos, Maisa Helena de Abreu Silva; Miguel, Marina Pacheco

    2016-09-01

    To compare the use of latex derivative and Aloe vera extract to wound healing. Twenty one rats were randomly divided into three groups and each one had a wound made by incision. The treatment consisted in: derivative of latex (GL), Aloe vera extract (GA) and saline solution (GC). The wound area was measured on the 7th, 14th and 21st days and macroscopic and microscopic evaluation were done. The comparison between the measurements of the wounds presented statistical difference in GC and GA from the 7th day of evaluation and GL from the 14th day. The extent of the wound was significantly smaller by the 7th day in GL. Histologically, in GL, the neovascularization was significant on the 7th, 14th and 21st days. On the 21st day the scar was large and little mature. In GA and GC, the findings were similar on the 7th, 14th and 21st days with a slight better organization of skin and collagen on the 21st in GA. Statistical analysis did not allow for the definition of the best topical agent. The latex had the highest angiogenesis, but a possible foreign body granuloma. Aloe vera has revealed a healing process adequated temporally in histology.

  1. Manganese-catalysed benzylic C(sp3)-H amination for late-stage functionalization.

    Science.gov (United States)

    Clark, Joseph R; Feng, Kaibo; Sookezian, Anasheh; White, M Christina

    2018-06-01

    Reactions that directly install nitrogen into C-H bonds of complex molecules are significant because of their potential to change the chemical and biological properties of a given compound. Although selective intramolecular C-H amination reactions are known, achieving high levels of reactivity while maintaining excellent site selectivity and functional-group tolerance remains a challenge for intermolecular C-H amination. Here, we report a manganese perchlorophthalocyanine catalyst [MnIII(ClPc)] for intermolecular benzylic C-H amination of bioactive molecules and natural products that proceeds with unprecedented levels of reactivity and site selectivity. In the presence of a Brønsted or Lewis acid, the [MnIII(ClPc)]-catalysed C-H amination demonstrates unique tolerance for tertiary amine, pyridine and benzimidazole functionalities. Mechanistic studies suggest that C-H amination likely proceeds through an electrophilic metallonitrene intermediate via a stepwise pathway where C-H cleavage is the rate-determining step of the reaction. Collectively, these mechanistic features contrast with previous base-metal-catalysed C-H aminations and provide new opportunities for tunable selectivities.

  2. Glucuronoyl Esterase Screening and Characterization Assays Utilizing Commercially Available Benzyl Glucuronic Acid Ester

    Directory of Open Access Journals (Sweden)

    Hampus Sunner

    2015-09-01

    Full Text Available Research on glucuronoyl esterases (GEs has been hampered by the lack of enzyme assays based on easily obtainable substrates. While benzyl d-glucuronic acid ester (BnGlcA is a commercially available substrate that can be used for GE assays, several considerations regarding substrate instability, limited solubility and low apparent affinities should be made. In this work we discuss the factors that are important when using BnGlcA for assaying GE activity and show how these can be applied when designing BnGlcA-based GE assays for different applications: a thin-layer chromatography assay for qualitative activity detection, a coupled-enzyme spectrophotometric assay that can be used for high-throughput screening or general activity determinations and a HPLC-based detection method allowing kinetic determinations. The three-level experimental procedure not merely facilitates routine, fast and simple biochemical characterizations but it can also give rise to the discovery of different GEs through an extensive screening of heterologous Genomic and Metagenomic expression libraries.

  3. Pertumbuhan Plantlet Anggrek Cattleya sp. dengan Perlakuan Benzyl Amino Purine pada Media Dasar Pupuk Daun Modifikasi

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    HESTIN YUSWANTI

    2015-09-01

    Full Text Available Growth of Plantlets of Cattleya Orchid on The Fooliar Fertilizer-Based Medium added with Benzyl Amino Purine. The aim of the current research was to investigate the appropriate concentrationof plant growth regulator BAP on the growth of Cattleya plantlet. The experiment was utilized a Randomized Completely Design with five treatments and six replications. The basal medium used was modification of foliar fertilizer of Growmore (trade mark with addition of fish emulsion, Vitamin B1 and active charcoal. BAP concentration used as treatment were 0 ppm, 0.5 ppm, 1.0 ppm, 1.5 ppm and 2.0 ppm. Variables observed were height, leaf number, root number, root length, fresh weight and dry weight of plantlets. The result showed that concentration of 1 ppm BAP resulted in the highest value for plantlet height (5.67 cm, leaf number (4.67, root length (2.07 cm, fresh weight (0.36 g and dry weight (0.043 g.

  4. Nanoemulsions of cancer chemopreventive agent benzyl isothiocyanate display enhanced solubility, dissolution, and permeability.

    Science.gov (United States)

    Qhattal, Hussaini Syed Sha; Wang, Shu; Salihima, Tri; Srivastava, Sanjay K; Liu, Xinli

    2011-12-14

    Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, is an effective chemopreventive agent. The objective of this study was to develop nanoemulsion formulations for the oral delivery of BITC. Optimized oil-in-water BITC nanoemulsions were prepared by a spontaneous self-nanoemulsification method and a homogenization-sonication method. Both nanoemulsions entrapped high amounts of BITC (15-17 mg/mL), with low polydispersity and good colloidal stability. The BITC nanoemulsions showed enhanced solubility and dissolution compared to pure BITC. These formulations markedly increased the apical to basolateral transport of BITC in Caco-2 cell monolayers. The apparent permeability values were 3.6 × 10(-6) cm/s for pure BITC and (1.1-1.3) × 10(-5) cm/s for BITC nanoemulsions. The nanoemulsions were easily taken up by human cancer cells A549 and SKOV-3 and inhibited tumor growth in vitro. This work shows for the first time that BITC can be formulated into nanoemulsions and may show promise in enhancing absorption and bioavailability.

  5. Preclinical evaluation of an {sup 18}F-trifluoroborate methionine derivative for glioma imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiangyu [Medical School of Southeast University, Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing (China); National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Liu, Zhibo; Zhang, Huimin; Li, Zhu; Niu, Gang; Chen, Xiaoyuan [National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Munasinghe, Jeeva P. [NIH, Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke, Bethesda, MD (United States); Teng, Gaojun [Medical School of Southeast University, Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing (China)

    2018-04-15

    {sup 11}C-methionine (MET) is one of the most commonly used amino acid tracers for PET imaging of brain tumors. In this study, we report an {sup 18}F-labeled boron-derived methionine analogue, denoted as {sup 18}F-B-MET, as a potential substitute of {sup 11}C-MET for glioma PET imaging. {sup 19}F-B-MET was synthesized from readily available chemicals according to our previous publication. For kit development, {sup 19}F-B-MET was aliquoted in quantities of 10 nmol for on-demand one-step labeling. The {sup 18}F-labeling was performed by {sup 18}F-{sup 19}F isotope exchange, and quality control was performed by both HPLC and radio-TLC. Uptake of the tracer was determined in GL26, C6 and U87 tumor cells. PET imaging and the biodistribution assay were performed on mice bearing subcutaneous or orthotopic C6 and U87 tumor xenografts. Starting with 740-1110 MBq {sup 18}F-fluoride, >370 MBq of {sup 18}F-B-MET was obtained in 25 min (n = 5) with >99% purity and high specific activity (>37 GBq/μmol). {sup 18}F-B-MET demonstrated excellent in vitro stability with <1% decomposition after incubation with plasma for 2 h. In vitro cell uptake assay showed that {sup 18}F-B-MET accumulated in tumor cells in a time dependent manner and could be competitively inhibited by natural methionine and other L-type transporter transported amino acids. In vivo biodistribution and imaging studies showed high tumor accumulation (2.99 ± 0.23 %ID/g, n = 6) compared with low uptake of brain (0.262 ± 0.05 %ID/g, n = 6) at 60 min after injection in a subcutaneous C6 tumor model. Orthotropic C6 and U87 tumors were clearly visualized with high tumor to brain ratios at 60 min post-injection, corroborating with tumor L-type amino acid transporter 1 (LAT-1) expression levels. {sup 18}F-B-MET was radiolabeled with high yield in a one-step labeling process, showed excellent pharmacokinetic properties in vivo, with high tumor-to-brain contrast. (orig.)

  6. Comparison and evaluation of satellite derived precipitation products for hydrological modeling of the Zambezi River Basin

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    T. Cohen Liechti

    2012-02-01

    Full Text Available In the framework of the African DAms ProjecT (ADAPT, an integrated water resource management study in the Zambezi Basin is currently under development. In view of the sparse gauging network for rainfall monitoring, the observations from spaceborne instrumentation currently produce the only available rainfall data for a large part of the basin.

    Three operational and acknowledged high resolution satellite derived estimates: the Tropical Rainfall Measuring Mission product 3B42 (TRMM 3B42, the Famine Early Warning System product 2.0 (FEWS RFE2.0 and the National Oceanic and Atmospheric Administration/Climate Prediction Centre (NOAA/CPC morphing technique (CMORPH are analyzed in terms of spatial and temporal repartition of the precipitations. They are compared to ground data for the wet seasons of the years 2003 to 2009 on a point to pixel basis at daily, 10-daily and monthly time steps and on a pixel to pixel basis for the wet seasons of the years 2003 to 2007 at monthly time steps.

    The general North-South gradient of precipitation is captured by all the analyzed products. Regarding the spatial heterogeneity, FEWS pixels are much more inter-correlated than TRMM and CMORPH pixels. For a rainfall homogeneity threshold criterion of 0.5 global mean correlation coefficient, the area of each sub-basin should not exceed a circle of 2.5° latitude/longitude radius for FEWS and a circle of 0.75° latitude/longitude radius for TRMM and CMORPH considering rectangular meshes.

    In terms of reliability, the correspondence of all estimates with ground data increases with the time step chosen for the analysis. The volume ratio computation indicates that CMORPH is overestimating the rainfall by nearly 50%. The statistics of TRMM and FEWS estimates show quite similar results.

    Due to its lower inter-correlation and longer data set, the TRMM 3B42 product is chosen as input for the hydraulic-hydrologic model of the basin.

  7. Synthesis and Antimicrobial Evaluation of Some Novel 2-(4-Chlorophenylimino) thiazolidin-4-one Derivatives

    Energy Technology Data Exchange (ETDEWEB)

    B' Bhatt, H.; Sharma, S. [Hemchandracharya North Gujarat Univ., Gujarat (India)

    2012-06-15

    A series of 2-(4-chlorophenylimino)-5-((3-(p-substituted phenyl)-1-phenyl-1H-pyrazol-4-yl) methylene) thiazolidin-4-one (3a-h) compounds were prepared from the 2-(4-chlorophenylimino) thiazolidin-4-one (1) and 1-phenyl-3-(psubstituted phenyl)-1H-pyrazole-4-carbaldehyde (2a-h). All compounds were characterized by elemental (C, H, N) analysis and spectral (FT-IR, {sup 1}H NMR and GC-MS) analysis. These newly synthesized compounds were screened for their antibacterial and antifungal activities. Antimicrobial activity was observed and evaluated against the bacterial strains like Eschericha coli (MTCC 443), Pseudomonas aeruginosa (MTCC 1688), Staphylococcus aureus (MTCC 96), Streptococcus pyogenes (MTCC 442) and against the fungal strains like Candida albicans (MTCC 227), Aspergillus niger (MTCC 282) and Aspergillus clavatus (MTCC 1323). All the synthesized compounds were found to possess moderate to excellent antimicrobial activity against above selected strains.

  8. Characterization of starch and other components from African crops and quality evaluation of derived products

    International Nuclear Information System (INIS)

    Quattrucci, E.; Acquistucci, R.; Carcea, M.; Cubadda, R.

    1997-01-01

    Research was carried out on African staple foods on characterization of components of cereals and tubers, and quality evaluation of foods manufactured from composite flours. Cereal starch, alimentary fiber and minerals from cassava were investigated. Starch was isolated under conditions of minimum damage from seeds of three sorghum and two fonio cultivars, and its physico-chemical properties were compared with commercial wheat starch. Fiber, ash and mineral content of samples of genetically improved varieties of cassava from Ghana were determined to understand the role of factors that influence texture of cooked products. Bread and pasta were produced from either triticale alone or in combination with different amounts of cassava flour, and by varying the amount of wheat flour. The organoleptic quality of the raw materials and final products were determined. (author). 15 refs, 10 tabs

  9. 3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis, molecular docking and biological evaluation.

    Science.gov (United States)

    Shi, Wei-Kang; Deng, Rui-Cheng; Wang, Peng-Fei; Yue, Qin-Qin; Liu, Qi; Ding, Kun-Ling; Yang, Mei-Hui; Zhang, Hong-Yu; Gong, Si-Hua; Deng, Min; Liu, Wen-Run; Feng, Qiu-Ju; Xiao, Zhu-Ping; Zhu, Hai-Liang

    2016-10-01

    Helicobacter pylori urease is involved in several physiologic responses such as stomach and duodenal ulcers, adenocarcinomas and stomach lymphomas. Thus, inhibition of urease is taken for a good chance to treat H. pylori-caused infections, we have therefore focused our efforts on seeking novel urease inhibitors. Here, a series of arylpropionylhydroxamic acids were synthesized and evaluated for urease inhibition. Out of these compounds, 3-(2-benzyloxy-5-chlorophenyl)-3-hydroxypropionylhydroxamic acid (d24) was the most active inhibitor with IC50 of 0.15±0.05μM, showing a mixed inhibition with both competitive and uncompetitive aspects. Non-linear fitting of kinetic data gives kinetics parameters of 0.13 and 0.12μg·mL(-1) for Ki and Ki', respectively. The plasma protein binding assays suggested that d24 exhibited moderate binding to human and rabbit plasma proteins. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Synthesis and Neuropharmacological Evaluation of Some Novel Quinoxaline 2, 3-Dione Derivatives

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    Selvaraj Jubie

    2012-01-01

    Full Text Available Quinoxaline-2, 3-dione obtained from cyclocondensation reaction of o-phenylene diamine with oxalic acid was reacted with three different ketones and formaldehyde to give the corresponding Mannich bases in satisfactory yield. Their structures were confirmed by using 1H NMR, IR, and mass analysis. In pharmacological evaluation, the synthesized compounds showed its curative effect against ethidium-bromide-induced demyelination in rats. For the purpose, different screening methods such as open field exploratory behavior test, rota rod test, grip strength test, beam walk test, and photo actometer test were performed. Ethidium bromide induction showed muscle weakness; muscle discoordination; loss of locomotor activity, and so forth, the synthesized drugs reversed all the above-mentioned neuromuscular disorders caused by ethidium bromide administration.

  11. Characterization of starch and other components from African crops and quality evaluation of derived products

    Energy Technology Data Exchange (ETDEWEB)

    Quattrucci, E; Acquistucci, R; Carcea, M [National Insti. of Nutrion, Rome (Italy); Cubadda, R [University of Molise, Campobasso (Italy)

    1997-07-01

    Research was carried out on African staple foods on characterization of components of cereals and tubers, and quality evaluation of foods manufactured from composite flours. Cereal starch, alimentary fiber and minerals from cassava were investigated. Starch was isolated under conditions of minimum damage from seeds of three sorghum and two fonio cultivars, and its physico-chemical properties were compared with commercial wheat starch. Fiber, ash and mineral content of samples of genetically improved varieties of cassava from Ghana were determined to understand the role of factors that influence texture of cooked products. Bread and pasta were produced from either triticale alone or in combination with different amounts of cassava flour, and by varying the amount of wheat flour. The organoleptic quality of the raw materials and final products were determined. (author). 15 refs, 10 tabs.

  12. Evaluation of the Leishmanicidal and Cytotoxic Potential of Essential Oils Derived from Ten Colombian Plants

    Directory of Open Access Journals (Sweden)

    JF Sanchez-Suarez

    2013-03-01

    Full Text Available Background: The leishmanicidal and cytotoxic activity of ten essential oils obtained from ten plant specimens were evaluated.Methods: Essential oils were obtained by the steam distillation of plant leaves without any prior processing. Cytotoxicity was tested on J774 macrophages and leishmanicidal activity was assessed against four species of Leishmania associated with cutaneous leishmaniasis. Results: Seven essential oils exhibited activity against Leishmania parasites, five of which were toxic against J774 macrophages. Selectivity indices of >6 and 13 were calculated for the essential oils of Ocimum basilicum and Origanum vulgare, respectively.Conclusion: The essential oil of Ocimum basilicum was active against promastigotes of Leishmania and innocuous to J774 macrophages at concentrations up to 1600 µg/mL and should be further investi­gated for leishmanicidal activity in others in vitro and in vivo experimental models.

  13. Including public perception data in the evaluation of the consequences of sewerage derived urban flooding.

    Science.gov (United States)

    Arthur, Scott; Crow, Helen; Karikas, Naoum

    2009-01-01

    This text reports research which was undertaken to assess the failure consequences associated with sewerage systems. In an effort to move away from considering only flood volume, depth or extent, the text will focus on how a survey of public opinion was used to inform the development of a consequence scoring methodology. The failure consequences considered range from internal flooding of properties, to road closure, environmental damage and odour problems. The text reports the extent to which experience of flooding influences perceptions of failure consequence and sewerage system management. It is also outlined how this data was used, along with other data sources, to construct an objective scoring process that can be used to evaluate failure consequence and readily prioritise sewerage maintenance.

  14. Psychophysical evaluation of a sanshool derivative (alkylamide and the elucidation of mechanisms subserving tingle.

    Directory of Open Access Journals (Sweden)

    Kelly C Albin

    2010-03-01

    Full Text Available Previous studies investigated the neural and molecular underpinnings of the tingle sensation evoked by sanshool and other natural or synthetic alkylamides. Currently, we sought to characterize the psychophysical properties associated with administration of these compounds. Like other chemesthetic stimuli, the synthetic tingle analog isobutylalkylamide (IBA evoked a sensation that was temporally dynamic. Repeated IBA application at short (30 sec interstimulus intervals (ISI resulted in a tingle sensation that increased across trials. Application at longer ISIs (approximately 30 min resulted in a sensation of decreased intensity consistent with self-desensitization. Prior treatment with the TRPV1 or TRPA1 agonists, capsaicin and mustard oil did not cross-desensitize the tingle sensation evoked by IBA suggesting that neither TRPV1 nor TRPA1 participate in the transduction mechanism sub-serving tingle. When evaluated over 30-min time period, lingual IBA evoked a sensation that was described initially as tingling and pungent but after approximately 15 min, as a cooling sensation. Further, we found that the sensation evoked by lingual IBA was potentiated by simultaneous application of cold (0 degrees C and cool (21 degrees C thermal stimuli but was unaffected by warm (33 degrees C and hot (41 degrees C temperatures. Finally, to test the hypothesis that the tingling sensation is subserved by the activation of mechanosensitve fibers, we evaluated lingual tactile thresholds in the presence and absence of lingual IBA. The presence of IBA significantly raised lingual tactile thresholds, whereas capsaicin did not, identifying a role for mechanosensitive fibers in conveying the tingle sensation evoked by sanshool-like compounds. Collectively, these results show that lingual alkylamide evokes a complex sensation that is temporally dynamic and consistent with in vitro and in vivo experiments suggesting these compounds activate mechanosensitve neurons via

  15. Flurbiprofen benzyl nitrate (NBS-242 inhibits the growth of A-431 human epidermoid carcinoma cells and targets ß-catenin

    Directory of Open Access Journals (Sweden)

    Nath N

    2013-05-01

    Full Text Available Niharika Nath,1,2 Xiaoping Liu,3 Lloydine Jacobs,1 Khosrow Kashfi1,3 1Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, NY, USA; 2Department of Life Sciences, New York Institute of Technology, New York, NY, USA; 3Division of Cancer Prevention, Department of Medicine, Stony Brook University, Stony Brook, NY, USA Background: The Wnt/ß-catenin/T cell factor (TCF signaling pathway is important in the development of nonmelanoma skin cancers (NMSCs. Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs are chemopreventive agents consisting of a traditional NSAID attached to an NO-releasing moiety through a chemical spacer. Previously we showed that an aromatic spacer enhanced the potency of a particular NO-NSAID compared to an aliphatic spacer. Methods: We synthesized an NO-releasing NSAID with an aromatic spacer (flurbiprofen benzyl nitrate, NBS-242, and using the human skin cancer cell line A-431, we evaluated its effects on cell kinetics, Wnt/ß-catenin, cyclin D1, and caspase-3. Results: NBS-242 inhibited the growth of A-431 cancer cells, being ~15-fold more potent than flurbiprofen and up to 5-fold more potent than NO-flurbiprofen with an aliphatic spacer, the half maximal inhibitory concentrations (IC50 for growth inhibition being 60 ± 4 µM, 320 ± 20 µM, and 880 ± 65 µM for NBS-242, NO-flurbiprofen, and flurbiprofen, respectively. This effect was associated with inhibition of proliferation, accumulation of cells in the G0/G1 phase of the cell cycle, and an increase in apoptotic cell population. NBS-242 cleaved ß-catenin both in the cytoplasm and the nucleus of A-431 cells. NBS-242 activated caspase-3 whose activation was reflected in the cleavage of procaspase-3. To test the functional consequence of ß-catenin cleavage, we determined the expression of cyclin D1, a Wnt-response gene. NBS-242 reduced cyclin D1 levels

  16. Chloroplast-derived vaccine antigens and biopharmaceuticals: protocols for expression, purification, or oral delivery and functional evaluation.

    Science.gov (United States)

    Singh, N Dolendro; Ding, Yi; Daniell, Henry

    2009-01-01

    Many vaccine antigens and biopharmaceutical proteins have been expressed at high levels via the chloroplast genome and their functionality has been evaluated using in vitro assays in cell cultures (i.e., macrophage lysis assay, inhibition of vesicular stomatitis virus-induced cytopathicity in baby hamster kidney cells, or inhibition of human HIV infection in TZM-BL cells) as well as protection after challenge with bacterial or viral pathogens or antitumor assays or delay the onset of insulitis in suitable animal models. Production of therapeutic proteins in chloroplasts eliminates the expensive fermentation technology. Moreover, oral delivery of chloroplast-derived therapeutic proteins eliminates expensive purification steps, cold storage, cold transportation, and delivery via sterile needles, thereby further decreasing their cost. In this chapter, we describe detailed protocols for chloroplast transformation including the construction of chloroplast transformation vectors, delivery of DNA into plant cells using particle bombardment, selection and regeneration of transformants by tissue culture, confirmation of transgene integration into the chloroplast genome and homoplasmy, evaluation of foreign gene expression, purification of foreign protein, or oral delivery via bioencapsulation, functional evaluation using in vitro and in vivo assays, and evaluation of immunity after challenge with pathogens in suitable animal models.

  17. Evaluation of derived compounds from sponges against induced oxidative stress in cortical neurons

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    Marta Leirós

    2014-06-01

    Firstly, the possible MKs protection against mitochondrial dysfunction caused by oxidative stress was tested. Mitochondrial function was analyzed by MTT, also correlated with neurons survival measurements (Varming et al., 1996. MKs, at the two chosen concentrations, were co-incubated with H2O2 (200 µM for 12h, and viability assays were performed. Results demonstrated that the viability of neurons treated with the oxidant decreased a 31.6 ± 2.0% (p 2O2 insults. TRMR test reveals a diminution of 33.6 ± 4.3% (p 2O2 treatments in neurons elevated ROS production in a 20.0 ± 2.5% (p 2O2 as previously described and ROS levels were measured. A reduction of ROS levels regarding the oxidant treatment was observed in MKs H, J, F and G treatments. In physiological conditions, low concentrations of H2O2 are transformed to water and molecular oxygen by GSH–peroxidase, with GSH as a proton donor. But when H2O2 amounts are high, they are instead eliminated by CAT. GSH is one of the antioxidant mitochondrial systems of protection against oxidative damage (Bains and Shaw, 1997. So to conclude the antioxidant research, MKs effects over GSH and CAT were evaluated. GSH is the main intracellular thiol in cells (Zampagni et al., 2012 and a thiol tracker was used to evaluate it. 12h H2O2 incubation produces a GSH level reduction of 25.8 ± 3.1% (p 2O2, as detailed above, and only MK J increased its levels to a 92.5 ± 9.4% (p = 0.048, achieving GSH basal amounts. Moreover the oxidation treatment decreases CAT activity in neurons in a 24.4 ± 5.5% (p < 0.01 however, the co-incubation with MKs increased CAT activity. MKs J, L and G treatments produced a significant elevation with a complete reestablishment of the activity. Neurons consume an elevated percentage of total body oxygen and consequently they are one of the most vulnerable cell populations to oxidative stress, which plays an important role in neurodegenerative pathology . After MKs evaluation in neurons under oxidative

  18. THE SPECIFICITY OF KERATEINE DERIVATIVES.

    Science.gov (United States)

    Pillemer, L; Ecker, E E; Martiensen, E W

    1939-09-30

    Carboxymethyl, alpha-carboxyethyl-, alpha-carboxy-n-propyl-, alpha-carboxyisopropyl-, alpha-carboxy-n-butyl, alpha-carboxyisobutyl, alpha-carboxyamyl-, benzyl-, and beta-phenylethylkeratemes were prepared from the parent protein, reduced keratin or kerateine. Chemical analysis disclosed that the various compounds differed in their isoelectric points and solubilities depending on the nature of the substituent group introduced. In general, it was found that in so far as could be determined, nearly all of the available sulfhydryl groups were substituted, while no detectable substitution of the free amino groups of the proteins occurred. The results of the serologic studies revealed that the kerateine derivatives acquired a new immunologie character dependent on the nature of the introduced determinant group. Inhibition tests confirmed the results obtained. Evidence was also produced to show that the grouping See PDF for structure may play a rôle in some of the reactions observed.

  19. Biotransformation of sclareolide by filamentous fungi: cytotoxic evaluations of the derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Cano, Arturo [Universidad Nacional Autonoma de Mexico, D.F. (Mexico). Facultad de Estudios Superiores Zaragoza; Ramirez-Apan, Maria Teresa; Delgado, Guillermo, E-mail: delgado@unam.m [Universidad Nacional Autonoma de Mexico, D.F. (Mexico)

    2011-07-01

    Sclareolide (1) was incubated with eight different species of filamentous fungi conventionally used for bio-oxidations. Compound 1 was metabolized with Aspergillus niger in medium A to yield 3-ketosclareolide (2) and 3b-hydroxysclareolide (4), while in medium B (containing major number of nutrients with respect to medium A), compounds 2, 4, 3{alpha},6{beta}-dihydroxysclareolide (16), 1-ketosclareolide (17), 3-keto-15-hydroxysclareolide (18) and 3{beta},15-dihydroxysclareolide (19) were obtained. The biotransformation products 16-19 were found to be new substances. Fermentation of 1 with Cunninghamella blackesleeana using medium A afforded 2 and 4, while using medium B yielded 2, 4, 16 and 17. Compounds 2, 4 and 17 were also obtained with Curvularia lunata. Biotransformation of 1 with Beauveria bassiana yielded 4 in satisfactory yield, with Rhizopus oligosporus and Mucor miehei afforded 2 and 4, while with R. nigricans and Fusarium moliniforme yielded 2, 4 and 16. Cytotoxic evaluation of 1 and the obtained products against selected human cancer cell lines (U251, PC-3, K562, HCT-15, MCF-7 and SKUL-1) indicated that 16 (3{alpha},6{beta}-dihydroxysclareolide) displayed moderate cytotoxic (IC{sub 50} < 100 {mu}M) against U251, PC-3, HCT-15 and MCF-7. (author)

  20. Identification of anthranilamide derivatives as potential factor Xa inhibitors: drug design, synthesis and biological evaluation.

    Science.gov (United States)

    Xing, Junhao; Yang, Lingyun; Li, Hui; Li, Qing; Zhao, Leilei; Wang, Xinning; Zhang, Yuan; Zhou, Muxing; Zhou, Jinpei; Zhang, Huibin

    2015-05-05

    The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against fXa. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 μM). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 × PT value of 8.7 μM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Biotransformation of sclareolide by filamentous fungi: cytotoxic evaluations of the derivatives

    International Nuclear Information System (INIS)

    Cano, Arturo

    2011-01-01

    Sclareolide (1) was incubated with eight different species of filamentous fungi conventionally used for bio-oxidations. Compound 1 was metabolized with Aspergillus niger in medium A to yield 3-ketosclareolide (2) and 3b-hydroxysclareolide (4), while in medium B (containing major number of nutrients with respect to medium A), compounds 2, 4, 3α,6β-dihydroxysclareolide (16), 1-ketosclareolide (17), 3-keto-15-hydroxysclareolide (18) and 3β,15-dihydroxysclareolide (19) were obtained. The biotransformation products 16-19 were found to be new substances. Fermentation of 1 with Cunninghamella blackesleeana using medium A afforded 2 and 4, while using medium B yielded 2, 4, 16 and 17. Compounds 2, 4 and 17 were also obtained with Curvularia lunata. Biotransformation of 1 with Beauveria bassiana yielded 4 in satisfactory yield, with Rhizopus oligosporus and Mucor miehei afforded 2 and 4, while with R. nigricans and Fusarium moliniforme yielded 2, 4 and 16. Cytotoxic evaluation of 1 and the obtained products against selected human cancer cell lines (U251, PC-3, K562, HCT-15, MCF-7 and SKUL-1) indicated that 16 (3α,6β-dihydroxysclareolide) displayed moderate cytotoxic (IC 50 < 100 μM) against U251, PC-3, HCT-15 and MCF-7. (author)

  2. Comprehensive evaluation of leukocyte lineage derived from human hematopoietic cells in humanized mice.

    Science.gov (United States)

    Takahashi, Masayuki; Tsujimura, Noriyuki; Otsuka, Kensuke; Yoshino, Tomoko; Mori, Tetsushi; Matsunaga, Tadashi; Nakasono, Satoshi

    2012-04-01

    Recently, humanized animals whereby a part of the animal is biologically engineered using human genes or cells have been utilized to overcome interspecific differences. Herein, we analyzed the detail of the differentiation states of various human leukocyte subpopulations in humanized mouse and evaluated comprehensively the similarity of the leukocyte lineage between humanized mice and humans. Humanized mice were established by transplanting human CD34(+) cord blood cells into irradiated severely immunodeficient NOD/Shi-scid/IL2Rγ(null) (NOG) mice, and the phenotypes of human cells contained in bone marrow, thymus, spleen and peripheral blood from the mice were analyzed at monthly intervals until 4 months after cell transplantation. The analysis revealed that transplanted human hematopoietic stem cells via the caudal vein homed and engrafted themselves successfully at the mouse bone marrow. Subsequently, the differentiated leukocytes migrated to the various tissues. Almost all of the leukocytes within the thymus were human cells. Furthermore, analysis of the differentiation states of human leukocytes in various tissues and organs indicated that it is highly likely that the human-like leukocyte lineage can be developed in mice. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  3. Synthesis, Characterization and Biological Evaluation of Transition Metal Complexes Derived from N, S Bidentate Ligands

    Directory of Open Access Journals (Sweden)

    Enis Nadia Md Yusof

    2015-05-01

    Full Text Available Two bidentate NS ligands were synthesized by the condensation reaction of S-2-methylbenzyldithiocarbazate (S2MBDTC with 2-methoxybenzaldehyde (2MB and 3-methoxybenzaldehyde (3MB. The ligands were reacted separately with acetates of Cu(II, Ni(II and Zn(II yielding 1:2 (metal:ligand complexes. The metal complexes formed were expected to have a general formula of [M(NS2] where M = Cu2+, Ni2+, and Zn2+. These compounds were characterized by elemental analysis, molar conductivity, magnetic susceptibility and various spectroscopic techniques. The magnetic susceptibility measurements and spectral results supported the predicted coordination geometry in which the Schiff bases behaved as bidentate NS donor ligands coordinating via the azomethine nitrogen and thiolate sulfur. The molecular structures of the isomeric S2M2MBH (1 and S2M3MBH (2 were established by X-ray crystallography to have very similar l-shaped structures. The Schiff bases and their metal complexes were evaluated for their biological activities against estrogen receptor-positive (MCF-7 and estrogen receptor-negative (MDA-MB-231 breast cancer cell lines. Only the Cu(II complexes showed marked cytotoxicity against the cancer cell lines. Both Schiff bases and other metal complexes were found to be inactive. In concordance with the cytotoxicity studies, the DNA binding studies indicated that Cu(II complexes have a strong DNA binding affinity.

  4. Selection and evaluation of soybean lines derived from gamma irradiation for rust resistance

    International Nuclear Information System (INIS)

    Smutkupt, S.; Wongpiyasatid, A.; Lamseejan, S.

    1983-01-01

    In 1979, seeds of 11 soybean cultivars were gamma irradiated with 15 and 30 krad. Treated and control seeds of each cultivar were planted in the rainy season. In the rainy season of 1980, M 3 populations were screened for rust resistance in Nong Hoi Valley and Mae Joe Experiment Station, both in Chiang Main province. The IWGSR rust rating system was used. Based upon the slow growth of rust on soybean plants, 6 and 115 plants were selected from 2,802 control plants and from 28,824 treated plants, respectively. Selected lines were evaluated in Nong Hoi Valley in the rainy season of 1981. Sixteen selections with average good seed yield per plant and low percentage of shrivelled seeds were obtained. Among them, two lines, namely G8586/Line number 81-1-072 and S.J. 4/Line number 81-1-037 gave the higher average seed yield per plant than other lines. They are at present in a preliminary yield trial in Chiang Mai. Chiang Mai. (author)

  5. Evaluation of new iodinated acridine derivatives for targeted radionuclide therapy of melanoma using {sup 125}I, an Auger electron emitter

    Energy Technology Data Exchange (ETDEWEB)

    Gardette, M.; Papon, J.; Bonnet, M.; Labarre, P.; Miot-Noirault, E.; Madelmont, J. C.; Chezal, J. M.; Moins, N. [UMR 990, INSERM, Universite d' Auvergne, Clermont-Ferrand (France); Desbois, N. [EA 3660, Universite de Bourgogne, Dijon (France); Wu, T. D.; Guerquin-Kern, J. L. [U 759 INSERM, Institute Curie, Orsay (France)

    2013-06-01

    The full text of the publication follows. The increasing incidence of melanoma and the lack of effective therapy on the disseminated form have led to an urgent need for new specific therapies. Several iodo-benzamides or analogs are known to possess specific affinity for melanoma tissue. New hetero-aromatic derivatives have been designed with a cytotoxic moiety and termed DNA intercalating agents. These compounds could be applied in targeted radionuclide therapy using {sup 125}I, Auger electrons emitter which gives high-energetic localized irradiation. Two iodinated acridine derivatives have been reported to present an in vivo kinetic profile conducive to application in targeted radionuclide therapy. The aim of the present study was to perform a preclinical evaluation of these compounds. The DNA intercalating property was confirmed for both compounds. After radiolabeling with {sup 125}I, the two compounds induced in vitro a significant radiotoxicity on B16F0 melanoma cells. The acridine compound, ICF01040, appeared more radio toxic than the acridone compound, ICF01035. While cellular uptake was similar for both compounds, SIMS analysis and in vitro protocol showed a stronger affinity for melanin with ICF01035, which was able to induce a predominant scavenging process in the melanosome and restrict access to the nucleus. Nevertheless, an important radiotoxicity was measured for the two compounds while the nuclear accumulation was low. Indeed, even if nuclear localization remains the main target sensitive to Auger electrons, the cell membrane remains sensitive to {sup 125}I decays. So, these compounds may induce secondary toxic effects of irradiation, such as membrane lipid damage. Conducted to current experiments are evaluate such hypothesis. Taken together, these results suggest that ICF01040 is a better candidate for application in targeted radionuclide therapy using {sup 125}I. The next step will be in vivo evaluation, where high tumoral vectorization gives

  6. Mechanochemical synthesis evaluation of nanocrystalline bone-derived bioceramic powder using for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Amirsalar Khandan

    2014-01-01

    Full Text Available Introduction: Bone tissue engineering proposes a suitable way to regenerate lost bones. Different materials have been considered for use in bone tissue engineering. Hydroxyapatite (HA is a significant success of bioceramics as a bone tissue repairing biomaterial. Among different bioceramic materials, recent interest has been risen on fluorinated hydroxyapatites, (FHA, Ca 10 (PO 4 6 F x (OH 2−x . Fluorine ions can promote apatite formation and improve the stability of HA in the biological environments. Therefore, they have been developed for bone tissue engineering. The aim of this study was to synthesize and characterize the FHA nanopowder via mechanochemical (MC methods. Materials and Methods: Natural hydroxyapatite (NHA 95.7 wt.% and calcium fluoride (CaF 2 powder 4.3 wt.% were used for synthesis of FHA. MC reaction was performed in the planetary milling balls using a porcelain cup and alumina balls. Ratio of balls to reactant materials was 15:1 at 400 rpm rotation speed. The structures of the powdered particles formed at different milling times were evaluated by X-ray diffraction (XRD, scanning electron microscopy (SEM and transmission electron microscopy (TEM. Results: Fabrication of FHA from natural sources like bovine bone achieved after 8 h ball milling with pure nanopowder. Conclusion: F− ion enhances the crystallization and mechanical properties of HA in formation of bone. The produced FHA was in nano-scale, and its crystal size was about 80-90 nm with sphere distribution in shape and size. FHA powder is a suitable biomaterial for bone tissue engineering.

  7. Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid Mediators of Inflammation to Ameliorate the Deleterious Effects of Blast Overpressure on Eye and Brain Visual Processing Centers in Rats

    Science.gov (United States)

    2014-10-01

    acid ( DHA ; 22:6ω-3) Eicosapentaenoic acid (EPA; 20:5ω-3) Lipoxin A4 Resolvin E1 Protectin DX Resolvin D1 LOX LOX LOX Structures and Endogenous Source...1 AD_________________ Award Number: W81XWH-12-2-0082 TITLE: Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid...Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid Mediators 5a. CONTRACT NUMBER of Inflammation to Ameliorate the Deleterious Effects of

  8. Improved anti-inflammatory activity of three new terpenoids derived, by systematic chemical modifications, from the abundant triterpenes of the flowery plant Calendula officinalis.

    Science.gov (United States)

    Neukirch, Hannes; D'Ambrosio, Michele; Sosa, Silvio; Altinier, Gianmario; Della Loggia, Roberto; Guerriero, Antonio

    2005-05-01

    Rings A, D and E of faradiol (1), and ring E of both arnidiol (10) and calenduladiol (4) have been subjected to various selective chemical manipulations to modify polarity, water affinity, H-bonding, sterics, and number of aromatic groups of these anti-inflammatory natural compounds. A total of 15 new and four known pentacyclic triterpenoids have been obtained in this way. Some 13 terpenoids were evaluated for their topical anti-inflammatory activities with respect to inhibition of croton oil induced ear oedema in mouse. Three derivatives of 1, the C(16) benzyl ether 15, the C(30) aldehyde 24, and the C(30) primary alcohol 25 showed significantly improved anti-inflammatory potencies, which is relevant for (future) structure-activity-relationship (SAR) studies.

  9. Assessment of antitumoral and antimicrobial effects of a maslinic acid derivative

    Directory of Open Access Journals (Sweden)

    Ioana Z. Pavel

    2016-12-01

    Full Text Available INTRODUCTION Maslinic acid, a naturally occurring triterpene, has been reported to possess several therapeutic effects including antioxidant, anti-inflammatory and antiparasitic properties. Structural changes of the compound led to the development of new derivatives in order to expand the spectrum of activities. OBJECTIVES AND BACKGROUND The present study was purposed to assess the in vitro antitumoral and antibacterial effects of a maslinic acid derivative, namely benzyl (2α, 3β 2,3-diacetoxy-olean-12- en-28-amide (EM2. MATERIALS AND METHODS Four compound concentrations (12.5, 25, 50 and 100 µM were evaluated for their cytotoxic effect on A375 human melanoma and B164A5 murine melanoma cell lines using the MTT assay. Furthermore, EM2 was tested on ten bacterial strains by means of agar disk diffusion method with the assessment of the inhibition zone diameters at 24h period of time. RESULTS EM2 elicited a dose-dependent cytotoxic effect on both melanoma cell lines. Regarding the antibacterial activity, EM2 determined a significant growth inhibition on Streptococcus pyogenes (20 ± 0.26 mm and Staphylococcus aureus (13 ± 0.19 mm. CONCLUSIONS The tested maslinic acid derivative is a promising antitumoral agent against skin cancer and antimicrobial agent against cocci bacteria. Graphical abstract: EM2 in vitro effects

  10. Comparative Evaluation of the Antimicrobial Efficacy of Three Immersion Chemical Disinfectants on Clinically Derived Poly(Vinyl Siloxane) Impressions.

    Science.gov (United States)

    Jeyapalan, Vidhya; Krishnan, Chitra Shankar; Ramasubramanian, Hariharan; Sampathkumar, Jayakrishnakumar; Azhagarasan, N S; Krishnan, Madhusudan

    2016-07-06

    To comparatively evaluate the antimicrobial efficacy of freshly prepared electrolyzed oxidizing water (EOW) with that of 2.4% glutaraldehyde (GA) and 1% sodium hypochlorite (SH) on clinically derived poly vinyl siloxane (PVS) impressions. Four clinically derived PVS impressions each were obtained from 10 subjects. One impression from each subject was randomly kept as control (group I), without disinfection. The remaining three impressions were randomly disinfected by immersion in either 2.4% GA (group II), 1% SH (group III), or freshly prepared EOW (group IV). The samples were subjected to microbial culture individually on brain heart infusion (BHI) agar medium. The organisms isolated were confirmed by visual examination and gram staining. Mean colony forming units (CFU) were counted, log 10 reduction obtained and compared. Data were statistically analyzed using one-way ANOVA, followed by multiple comparisons using Tukey-HSD post hoc tests (p < 0.05). Streptococci, Staphylococci, Pseudomonas, Candida, Proteus, Klebsiella, and E. coli were isolated from all impressions including the controls, except those disinfected by EOW. All three disinfectants showed significant reduction in CFU and log 10 reduction values as compared to the controls. EOW showed significantly higher reduction in log 10 values compared to GA and SH, whereas GA and SH showed similar reductions. EOW, GA, and SH showed kill rates of 100%, 99.60%, and 99.82%, respectively. EOW showed significant antimicrobial efficacy as evidenced by reduction in log 10 values when used as an immersion disinfectant for PVS impressions when compared with the results obtained using GA and SH. These results need further investigation. EOW shows high antimicrobial efficacy when used as an immersion disinfectant as compared to GA and SH for clinically derived PVS impressions. © 2016 by the American College of Prosthodontists.

  11. Radiosynthesis and biological evaluation of an 18F-labeled derivative of the novel pyrazolopyrimidine sedative-hypnotic agent indiplon

    International Nuclear Information System (INIS)

    Hoepping, Alexander; Scheunemann, Matthias; Fischer, Steffen; Deuther-Conrad, Winnie; Hiller, Achim; Wegner, Florian; Diekers, Michael; Steinbach, Joerg; Brust, Peter

    2007-01-01

    Introduction: Gamma amino butyric acid type A (GABA A ) receptors are involved in a variety of neurological and psychiatric diseases, which have promoted the development and use of radiotracers for positron emission tomography imaging. Radiolabeled benzodiazepine antagonists such as flumazenil have most extensively been used for this purpose so far. Recently, the non-benzodiazepine pyrazolopyrimidine derivative indiplon with higher specificity for the α 1 subtype of the GABA A receptor has been introduced for treatment of insomnia. The aim of this study was the development and biological evaluation of an 18 F-labeled derivative of indiplon. Methods: Both [ 18 F]fluoro-indiplon and its labeling precursor were synthesized by two-step procedures starting from indiplon. The radiosynthesis of [ 18 F]fluoro-indiplon was performed using the bromoacetyl precursor followed by multiple-stage purification using semipreparative HPLC and solid phase extraction. Stability, partition coefficients, binding affinities and regional brain binding were determined in vitro. Biodistribution and radiotracer metabolism were studied in vivo. Results: [ 18 F]Fluoro-indiplon was readily accessible in good yields (38-43%), with high purity and high specific radioactivity (>150 GBq/μmol). It displays high in vitro stability and moderate lipophilicity. [ 18 F]Fluoro-indiplon has an affinity to GABA A receptors comparable to indiplon (K i =8.0 nM vs. 3.4 nM). In vitro autoradiography indicates high [ 18 F]fluoro-indiplon binding in regions with high densities of GABA A receptors. However, ex vivo autoradiography and organ distribution studies show no evidence of specific binding of [ 18 F]fluoro-indiplon. Furthermore, the radiotracer is rapidly metabolized with high accumulation of labeled metabolites in the brain. Conclusions: Although [ 18 F]fluoro-indiplon shows good in vitro features, it is not suitable for in vivo imaging studies because of its metabolism. Structural modifications are

  12. Estudo de propriedades de PVC modificado com grupos alquila e benzila Study of the properties of PVC modified through substitution by alkyl and benzyl groups

    Directory of Open Access Journals (Sweden)

    G. M Vinhas

    2005-07-01

    variety of transformation processes. The resin is non toxic and inert, therefore the choice of additives having these properties allows for the fabrication of films for food packaging and medical products. On the other hand, the PVC properties can be altered by sterilization processes, in particular through gamma radiation. In this paper we present a study of the flexibility and stability to gamma radiation of chemically-modified PVC. PVC was modified through substitution of chlorine by alkyl and benzyl groups using Grignard reagents. Modified PVC samples were characterized by proton nuclear magnetic resonance (¹H NMR spectroscopy, infrared spectroscopy and differential scanning calorimetric analyses. Degradation of the polymers when submitted to gamma irradiation was evaluated by their viscometric parameters. The modified PVCs generally presented higher stability to gamma radiation than the original polymer. The benzyl substituted polymer exhibited the highest stability when submitted to the sterilization dosage of 25 kGy. The modified PVCs presented glass transition temperatures slightly lower than the original polymer pointing to an increase in flexibility due to the presence of alkyl and benzyl groups as substituents in the main chain.

  13. Evaluation of the National Research Council (2001) dairy model and derivation of new prediction equations. 1. Digestibility of fiber, fat, protein, and nonfiber carbohydrate.

    Science.gov (United States)

    White, R R; Roman-Garcia, Y; Firkins, J L; VandeHaar, M J; Armentano, L E; Weiss, W P; McGill, T; Garnett, R; Hanigan, M D

    2017-05-01

    Evaluation of ration balancing systems such as the National Research Council (NRC) Nutrient Requirements series is important for improving predictions of animal nutrient requirements and advancing feeding strategies. This work used a literature data set (n = 550) to evaluate predictions of total-tract digested neutral detergent fiber (NDF), fatty acid (FA), crude protein (CP), and nonfiber carbohydrate (NFC) estimated by the NRC (2001) dairy model. Mean biases suggested that the NRC (2001) lactating cow model overestimated true FA and CP digestibility by 26 and 7%, respectively, and under-predicted NDF digestibility by 16%. All NRC (2001) estimates had notable mean and slope biases and large root mean squared prediction error (RMSPE), and concordance (CCC) ranged from poor to good. Predicting NDF digestibility with independent equations for legumes, corn silage, other forages, and nonforage feeds improved CCC (0.85 vs. 0.76) compared with the re-derived NRC (2001) equation form (NRC equation with parameter estimates re-derived against this data set). Separate FA digestion coefficients were derived for different fat supplements (animal fats, oils, and other fat types) and for the basal diet. This equation returned improved (from 0.76 to 0.94) CCC compared with the re-derived NRC (2001) equation form. Unique CP digestibility equations were derived for forages, animal protein feeds, plant protein feeds, and other feeds, which improved CCC compared with the re-derived NRC (2001) equation form (0.74 to 0.85). New NFC digestibility coefficients were derived for grain-specific starch digestibilities, with residual organic matter assumed to be 98% digestible. A Monte Carlo cross-validation was performed to evaluate repeatability of model fit. In this procedure, data were randomly subsetted 500 times into derivation (60%) and evaluation (40%) data sets, and equations were derived using the derivation data and then evaluated against the independent evaluation data. Models

  14. Evaluation of motor neuron differentiation potential of human umbilical cord blood- derived mesenchymal stem cells, in vitro.

    Science.gov (United States)

    Yousefi, Behnam; Sanooghi, Davood; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Latifi, Nourahmad

    2017-04-01

    Many people suffer from spinal cord injuries annually. These deficits usually threaten the quality of life of patients. As a postpartum medically waste product, human Umbilical Cord Blood (UCB) is a rich source of stem cells with self- renewal properties and neural differentiation capacity which made it useful in regenerative medicine. Since there is no report on potential of human umbilical cord blood-derived mesenchymal stem cells into motor neurons, we set out to evaluate the differentiation properties of these cells into motor neuron-like cells through administration of Retinoic Acid(RA), Sonic Hedgehog(Shh) and BDNF using a three- step in vitro procedure. The results were evaluated using Real-time PCR, Flowcytometry and Immunocytochemistry for two weeks. Our data showed that the cells changed into bipolar morphology and could express markers related to motor neuron; including Hb-9, Pax-6, Islet-1, NF-H, ChAT at the level of mRNA and protein. We could also quantitatively evaluate the expression of Islet-1, ChAT and NF-H at 7 and 14days post- induction using flowcytometry. It is concluded that human UCB-MSCs is potent to express motor neuron- related markers in the presence of RA, Shh and BDNF through a three- step protocol; thus it could be a suitable cell candidate for regeneration of motor neurons in spinal cord injuries. Copyright © 2017. Published by Elsevier B.V.

  15. Conditioned Medium of Bone Marrow-Derived Mesenchymal Stromal Cells as a Therapeutic Approach to Neuropathic Pain: A Preclinical Evaluation

    Directory of Open Access Journals (Sweden)

    Kelly Barbosa Gama

    2018-01-01

    Full Text Available Neuropathic pain is a type of chronic pain caused by injury or dysfunction of the nervous system, without effective therapeutic approaches. Mesenchymal stromal cells (MSCs, through their paracrine action, have great potential in the treatment of this syndrome. In the present study, the therapeutic potential of MSC-derived conditioned medium (CM was investigated in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL. PSL mice were treated by endovenous route with bone marrow-derived MSCs (1 × 106, CM, or vehicle. Gabapentin was the reference drug. Twelve hours after administration, neuropathic mice treated with CM exhibited an antinociceptive effect that was maintained throughout the evaluation period. MSCs also induced nonreversed antinociception, while gabapentin induced short-lasting antinociception. The levels of IL-1β, TNF-α, and IL-6 were reduced, while IL-10 was enhanced on sciatic nerve and spinal cord by treatment with CM and MSCs. Preliminary analysis of the CM secretome revealed the presence of growth factors and cytokines likely involved in the antinociception. In conclusion, the CM, similar to injection of live cells, produces a powerful and long-lasting antinociceptive effect on neuropathic pain, which is related with modulatory properties on peripheral and central levels of cytokines involved with the maintenance of this syndrome.

  16. Preliminary evaluation of two radioiodinated maleimide derivatives targeting peripheral and membrane sulfhydryl groups for in vitro cell labeling

    Energy Technology Data Exchange (ETDEWEB)

    Amartey, John K., E-mail: amarjk48@hotmail.co [Cyclotron and Radiopharmaceuticals Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Parhar, Ranjit S. [Biological and Medical Research Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Shi, Yufei [Genetics Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Al-Mohanna, Futwan [Biological and Medical Research Department, P.O. Box 3354, Riyadh 11211 (Saudi Arabia)

    2011-01-15

    A factor impeding the advancement of cell mediated therapy is the inability to track these cells in vivo by noninvasive techniques. It has been shown that cells express high levels of sulfhydryl groups. We sought to explore these groups to covalently label cells with radiolabeled maleimide derivatives. Two maleimide derivatives; N-[2-(2,5-dioxoazolinyl)ethyl](5-iodo(3-pyridyl))carboxamide and N-[2-(2,5-dioxoazolinyl)ethyl](3-iodophenyl)carboxamide ([{sup 125}I]-4 and [{sup 125}I]-8) were synthesized and radioiodinated. These compounds were evaluated for in vitro binding to neutrophils, endothelial and mesenchymal stem cells, and biodistribution of the radiolabeled stem cells in nude mice. These radiotracers were obtained in moderate to high radiochemical yields. Binding to cells were moderate (20-60%/10{sup 6} cells) and the label was retained, although washout (an average of 18-55%) was observed depending on the cell type and the tracer used. The labeled cells initially localized in well perfused organs and at a later time showed a general distribution as expected. The novel tracers labeled several cell types and shown that the stability of the label and viability of the cells were maintained in vitro and in vivo for a reasonable period and warrant further in vivo investigation.

  17. Use of the SONET Score to Evaluate High Volume Emergency Department Overcrowding: A Prospective Derivation and Validation Study

    Directory of Open Access Journals (Sweden)

    Hao Wang

    2015-01-01

    Full Text Available Background. The accuracy and utility of current Emergency Department (ED crowding estimation tools remain uncertain in EDs with high annual volumes. We aimed at deriving a more accurate tool to evaluate overcrowding in a high volume ED setting and determine the association between ED overcrowding and patient care outcomes. Methods. A novel scoring tool (SONET: Severely overcrowded-Overcrowded-Not overcrowded Estimation Tool was developed and validated in two EDs with both annual volumes exceeding 100,000. Patient care outcomes including the number of left without being seen (LWBS patients, average length of ED stay, ED 72-hour returns, and mortality were compared under the different crowding statuses. Results. The total number of ED patients, the number of mechanically ventilated patients, and patient acuity levels were independent risk factors affecting ED overcrowding. SONET was derived and found to better differentiate severely overcrowded, overcrowded, and not overcrowded statuses with similar results validated externally. In addition, SONET scores correlated with increased length of ED stay, number of LWBS patients, and ED 72-hour returns. Conclusions. SONET might be a better fit to determine high volume ED overcrowding. ED overcrowding negatively impacts patient care operations and often produces poor patient perceptions of standardized care delivery.

  18. Synthesis and preliminary evaluation of novel 99mTc-labeled folate derivative via click reaction for SPECT imaging

    International Nuclear Information System (INIS)

    Guo, Zhide; Zhang, Pu; Song, Manli; Wu, Xiaowei; Liu, Chang; Zhao, Zuoquan; Lu, Jie; Zhang, Xianzhong

    2014-01-01

    The folate receptor is over expressed in a wide variety of human tumors. In this study, a novel 99m Tc-labeled folate derivative ( 99m Tc-HYNIC-T-FA) was synthesized as a potential FR-targeting imaging probe and its efficiency was evaluated. This 99m Tc-complex could be obtained through practical manner and showed improved in vivo characteristics compared with other radiofolates. Thus, this novel 99m Tc-HYNIC-T-FA compound could serve as a potential imaging agent for folate receptor positive tumors. - Highlights: • An efficient synthetic strategy (click chemistry) was used to improve the overall efficiency. • 99m Tc-HYNIC-T-FA showed a high tumor uptake but low no-target tissues uptakes. • Excellent tumor-to-kidney ratio was achieved by injecting PMX. • A kit formulation was developed to obtain the desired product without any purification

  19. Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives Bearing a Heterocyclic Ring at 4/5 Position

    International Nuclear Information System (INIS)

    Wubulikasimu, Reyila; Yang, Yanbing; Xue, Fei; Luo, Xianjin; Shao, Dongping; Li, Yuhuan; Gao, Rongmei; Ye, Weidong

    2013-01-01

    A series of novel benzimidazole derivatives bearing a heterocyclic ring as oxadiazole (21-32), thiadiazole (33-34), triazole (35-36) were synthesized and evaluated for their activities against Coxsackie virus B3 and B6 in Vero cells. Compounds 21-26, 31-36 with moieties of 2'-pyridyl, 3'-pyridyl and 4'-pyridyl at the 2-position and oxadiazoles, thiadiazole, or triazole substituent at the 4- or 5-position generally displayed activities against CVB3 and CVB6. Especially compound 24 (IC 50 = 1.08 μg/mL, SI = 61.7 against CVB3) was the promising candidate as lead compound for anti-enteroviral drug. It was observed in the incorporation of heterocyclic rings in benzimidazole at the 5-position could enhance their biological activities

  20. Synthesis and evaluation of new organic and phosphorous derivatives against ionizing radiation: study of the in vitro mechanism of action

    International Nuclear Information System (INIS)

    Prouillac, C.

    2006-10-01

    This work falls under a research program. The aim was to synthesize new organic phosphorylated compounds having an interesting radio pharmacological activity without toxicity. That is why, we carried out the synthesis of new benzothiazole and thiadiazole N-substituted derivatives as thiols, amino thiols, acids thio-sulfonic and phosphoro thioates. All these compounds were characterized by NMR (proton, carbon, phosphorus, 2D), by mass spectrometry, elementary analyzes and for some of them by diffraction of x-rays. The activity of the majority of them was evaluated by in vitro tests. The experimental results were confirmed by theoretical study: the aim of D.F.T. calculation was the study of the mechanism of capture of the free radicals by our compounds. In addition, a study of relation structure activity (Q.S.A.R.) was carried out. Our results allow us to create a model making it possible to establish structure-activity relationship. (author)

  1. A novel mesoporous sulfated zirconium solid acid catalyst for Friedel-Crafts benzylation reaction

    International Nuclear Information System (INIS)

    Miao, Zhichao; Zhou, Jin; Zhao, Jinping; Liu, Dandan; Bi, Xu; Chou, Lingjun; Zhuo, Shuping

    2017-01-01

    Highlights: • A novel mesoporous ZrO_2/SO_4"2"− has been prepared via a facile one-pot EISA strategy. • The M-ZrO_2/SO_4"2"− exhibited excellent textural and acidic properties. • The introduced S species were homogeneously dispersed in mesoporous skeleton. • The M-ZrO_2/SO_4"2"− exhibited excellent catalytic performance and reusability. - Abstract: In this paper, a novel mesoporous sulfated zirconium (M-ZrO_2/SO_4"2"−) has been gotten by one-pot evaporation-induced self-assembly (one-pot EISA) strategy. The SXRD, N_2-physisorption and TEM characterization techniques indicated that M-ZrO_2/SO_4"2"− possessed distinct mesostructure with big specific surface area (133.5 m"2 g"−"1), large pore volume (0.18 cm"3 g"−"1) and narrow pore size distribution (4.90 nm). Moreover, the existing states and the influence in mesostructure of introduced S species were detailedly investigated by the XRD, N_2-physisorption, TEM, TG-DSC, FT-IR and XPS techniques and the results showed that the S species, which existed as the type of SO_4"2"−, improved the textural properties of prepared materials. In addition, the NH_3-TPD and IR spectra of adsorbed pyridine indicated the existence of strong Brønsted and Lewis acid sites in M-ZrO_2/SO_4"2"− even evacuated at 400 °C. Furthermore, the M-ZrO_2/SO_4"2"− was used as a promise solid acid catalyst and displayed excellent catalytic performance and reusability in Friedel-Crafts benzylation reaction.

  2. Contact allergy to isoeugenol and its derivatives

    DEFF Research Database (Denmark)

    Tanaka, Susumu; Royds, C; Buckley, Christopher D

    2004-01-01

    A total of 2261 (808 male, 1453 female) consecutive patients attending contact dermatitis clinics were patch tested to isoeugenol and its derivatives listed in the EU Inventory of Fragrance Ingredients. Positive reactions were found to isoeugenol in 40, transisoeugenol in 40, isoeugenyl acetate...... and 15/16 of those to isoeugenyl phenylacetate but in none of those 6 positive to isoeugenyl methyl ether and in neither of those 2 positive to benzyl isoeugenyl ether. Concomitant contact allergy between isoeugenol and its derivatives may occur through chemical cross-reactivity or local skin metabolism...... of the derivatives. It is more commonly observed with the esters rather than the ethers. Isoeugenyl acetate has been proposed as an alternative to isoeugenol, but there is a high degree of concomitant reactivity with isoeugenol....

  3. The Effects of Foliar Application of Benzyl Adenine, Ascorbic Acid and Thiamine on Some Morphological and Biochemical Characteristics of Petunia (Petunia hybrida

    Directory of Open Access Journals (Sweden)

    M. Salehi

    2016-05-01

    Full Text Available The improvement of growth and flowering of petunia as one of the most popular and cultivated bedding plants in Iran, is of significant importance. Thus, a CRD experiment with five replications was conducted at the Research Greenhouse of Shahid Bahonar University, Kerman, Iran.  From 48 days after sowing, when the seedlings had 5-6 true leaves, the seedlings were sprayed with  thiamine (0 and 100 mgL-1, ascorbic acid (0 and 100 mg L-1 and benzyl adenine (0 and 200 mg L-1 at 4 steps during  growth and development. The results indicated that the treatment of ascorbic acid with thiamine and benzyl adenine led to 2.5 and 3.5-fold increases in the number and length of lateral shoots compared to control treatment. The greatest fresh weight was obtained with ascorbic acid with thiamine and benzyl adenine treatment which led to a 2.5-fold increase in this trait, compared to the control. The highest dry weight was achieved in benzyl adenine treatment. The greatest vase-life and flower diameter were found with ascorbic acid (100 mg L-1, thiamine (100 mg L-1 and benzyl adenine (200 mg L-1 treatments in an extent that the flower longevity and diameter were increased by 83% and 72%, respectively, in comparison to control. Furthermore, chlorophyll a, chlorophyll b, total chlorophyll, carotenoids and reduced sugars concentrations were significantly increased by the foliar-applied compounds compared to control.

  4. Evaluation of the use of various rat strains for immunogenic potency tests of Sabin-derived inactivated polio vaccines.

    Science.gov (United States)

    Someya, Yuichi; Ami, Yasushi; Takai-Todaka, Reiko; Fujimoto, Akira; Haga, Kei; Murakami, Kosuke; Fujii, Yoshiki; Shirato, Haruko; Oka, Tomoichiro; Shimoike, Takashi; Katayama, Kazuhiko; Wakita, Takaji

    2018-03-01

    Slc:Wistar rats have been the only strain used in Japan for purpose of evaluating a national reference vaccine for the Sabin-derived inactivated polio vaccine (sIPV) and the immunogenicity of sIPV-containing products. However, following the discovery that the Slc:Wistar strain was genetically related to the Fischer 344 strain, other "real" Wistar strains, such as Crlj:WI, that are available worldwide were tested in terms of their usefulness in evaluating the immunogenicity of the past and current lots of a national reference vaccine. The response of the Crlj:WI rats against the serotype 1 of sIPV was comparable to that of the Slc:Wistar rats, while the Crlj:WI rats exhibited a higher level of response against the serotypes 2 and 3. The immunogenic potency units of a national reference vaccine determined using the Slc:Wistar rats were reproduced on tests using the Crlj:WI rats. These results indicate that a titer of the neutralizing antibody obtained in response to a given dose of sIPV cannot be directly compared between these two rat strains, but that, more importantly, the potency units are almost equivalent for the two rat strains. Copyright © 2018 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  5. Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid Derivative for PET Imaging the Cannabinoid Type 2 Receptor

    Directory of Open Access Journals (Sweden)

    Linjing Mu

    2014-03-01

    Full Text Available Cannabinoid receptor subtype 2 (CB2 has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer’s disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated. [11C]KP23 was obtained in 10%–25% radiochemical yield (decay corrected and 99% radiochemical purity. It showed high stability in phosphate buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen slices, as spleen expresses a high physiological expression of CB2 receptors, demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats. In conclusion, [11C]KP23 showed promising in vitro and in vivo characteristics. Further evaluation with diseased animal model which has higher CB2 expression levels in the brain is warranted.

  6. Evaluation of Chemical Warfare Agent Percutaneous Vapor Toxicity: Derivation of Toxicity Guidelines for Assessing Chemical Protective Ensembles.

    Energy Technology Data Exchange (ETDEWEB)

    Watson, A.P.

    2003-07-24

    Percutaneous vapor toxicity guidelines are provided for assessment and selection of chemical protective ensembles (CPEs) to be used by civilian and military first responders operating in a chemical warfare agent vapor environment. The agents evaluated include the G-series and VX nerve agents, the vesicant sulfur mustard (agent HD) and, to a lesser extent, the vesicant Lewisite (agent L). The focus of this evaluation is percutaneous vapor permeation of CPEs and the resulting skin absorption, as inhalation and ocular exposures are assumed to be largely eliminated through use of SCBA and full-face protective masks. Selection of appropriately protective CPE designs and materials incorporates a variety of test parameters to ensure operability, practicality, and adequacy. One aspect of adequacy assessment should be based on systems tests, which focus on effective protection of the most vulnerable body regions (e.g., the groin area), as identified in this analysis. The toxicity range of agent-specific cumulative exposures (Cts) derived in this analysis can be used as decision guidelines for CPE acceptance, in conjunction with weighting consideration towards more susceptible body regions. This toxicity range is bounded by the percutaneous vapor estimated minimal effect (EME{sub pv}) Ct (as the lower end) and the 1% population threshold effect (ECt{sub 01}) estimate. Assumptions of exposure duration used in CPE certification should consider that each agent-specific percutaneous vapor cumulative exposure Ct for a given endpoint is a constant for exposure durations between 30 min and 2 hours.

  7. In Vitro Evaluation of Sub-Lethal Concentrations of Plant-Derived Antifungal Compounds on FUSARIA Growth and Mycotoxin Production

    Directory of Open Access Journals (Sweden)

    Caterina Morcia

    2017-07-01

    Full Text Available Phytopathogenic fungi can lead to significant cereal yield losses, also producing mycotoxins dangerous for human and animal health. The fungal control based on the use of synthetic fungicides can be complemented by "green" methods for crop protection, based on the use of natural products. In this frame, the antifungal activities of bergamot and lemon essential oils and of five natural compounds recurrent in essential oils (citronellal, citral, cinnamaldehyde, cuminaldehyde and limonene have been evaluated against three species of mycotoxigenic fungi (Fusarium sporotrichioides, F. graminearum and F. langsethiae responsible for Fusarium Head Blight in small-grain cereals. The natural products concentrations effective for reducing or inhibiting the in vitro fungal growth were determined for each fungal species and the following scale of potency was found: cinnamaldehyde > cuminaldehyde > citral > citronellal > bergamot oil > limonene > lemon oil. Moreover, the in vitro mycotoxin productions of the three Fusaria strains exposed to sub-lethal concentrations of the seven products was evaluated. The three fungal species showed variability in response to the treatments, both in terms of inhibition of mycelial growth and in terms of modulation of mycotoxin production that can be enhanced by sub-lethal concentrations of some natural products. This last finding must be taken into account in the frame of an open field application of some plant-derived fungicides.

  8. Benzyl isothiocyanate, a major component from the roots of Salvadora persica is highly active against Gram-negative bacteria.

    Directory of Open Access Journals (Sweden)

    Abier Sofrata

    Full Text Available Plants produce a number of antimicrobial substances and the roots of the shrub Salvadora persica have been demonstrated to possess antimicrobial activity. Sticks from the roots of S. persica, Miswak sticks, have been used for centuries as a traditional method of cleaning teeth. Diverging reports on the chemical nature and antimicrobial repertoire of the chewing sticks from S. persica led us to explore its antibacterial properties against a panel of pathogenic or commensal bacteria and to identify the antibacterial component/s by methodical chemical characterization. S. persica root essential oil was prepared by steam distillation and solid-phase microextraction was used to sample volatiles released from fresh root. The active compound was identified by gas chromatography-mass spectrometry and antibacterial assays. The antibacterial compound was isolated using medium-pressure liquid chromatography. Transmission electron microscopy was used to visualize the effect on bacterial cells. The main antibacterial component of both S. persica root extracts and volatiles was benzyl isothiocyanate. Root extracts as well as commercial synthetic benzyl isothiocyanate exhibited rapid and strong bactericidal effect against oral pathogens involved in periodontal disease as well as against other Gram-negative bacteria, while Gram-positive bacteria mainly displayed growth inhibition or remained unaffected. The short exposure needed to obtain bactericidal effect implies that the chewing sticks and the essential oil may have a specific role in treatment of periodontal disease in reducing Gram-negative periodontal pathogens. Our results indicate the need for further investigation into the mechanism of the specific killing of Gram-negative bacteria by S. persica root stick extracts and its active component benzyl isothiocyanate.

  9. Reactions of 5-Aroylmethylene-3-benzyl-4-oxo-2-thioxo-1,3-thiazolidines with Nitrile Oxides

    Directory of Open Access Journals (Sweden)

    Ahmed S. A. Youssef

    2001-05-01

    Full Text Available E,Z-5-Aroylmethylene-3-benzyl-4-oxo-2-thioxo-1,3-thiazolidines (3a-c react with 4-methoxy and 4-chlorophenylnitrile oxides (4a and b in pyridine solution to afford one or more of the following compounds: Z-3, Z-2,4-dioxo analogues 5 and 3,6-diaryl-1,4,2,5-dioxadiazines (6a-b. The interconversion route is discussed and the structures of all of the synthesised compounds are proven by microanalytical and spectral data.

  10. 3-Benzyl-6-bromo-2-(2-furyl-3H-imidazo[4,5-b]pyridine

    Directory of Open Access Journals (Sweden)

    Younès Ouzidan

    2010-07-01

    Full Text Available In the title molecule, C17H12BrN3O, the imidazopyridine ring system is almost coplanar with the furan ring [dihedral angle = 2.0 (3°]. The benzyl phenyl ring is oriented at dihedral angles of 85.2 (2 and 85.5 (1°, respectively, with respect to the furan ring and the imidazopyridine ring system. In the crystal, molecules are linked into chains propagating along the b axis by C—H...N hydrogen bonds. Adjacent chains are linked via short Br...Br contacts [3.493 (1 Å].

  11. Modification of Carboxymethyl Chitosan Film by Blending with Poly(benzyl L-glutamate)-block-poly(ethylene glycol) Copolymer

    International Nuclear Information System (INIS)

    Zhu, G.Z.; Gao, Q.C.; Liu, Y.Y.

    2013-01-01

    A series of water-soluble carboxymethyl chitosan (CMCS)/poly(benzyl L-glutamate)-block-poly(ethylene glycol) (PBLG-b-PEG) blend films with various CMCS/PBLG-b-PEG mol ratios were prepared by pervaporation method. Morphologies of CMCS/PBLG-b-PEG blend films were researched by scanning electron microscopy (SEM). Thermal, mechanical, and chemical properties of CMCS/PBLG-b-PEG blend films were investigated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), tensile tests, and contact angle tests. It was revealed that the introduction of PBLG-b-PEG segments could greatly affect the morphology and the properties of CMCS films. (author)

  12. Study of the Chemical Mechanism Involved in the Formation of Tungstite in Benzyl Alcohol by the Advanced QEXAFS Technique

    DEFF Research Database (Denmark)

    Olliges‐Stadler, Inga; Stötzel, Jan; Koziej, Dorota

    2012-01-01

    Insight into the complex chemical mechanism for the formation of tungstite nanoparticles obtained by the reaction of tungsten hexachloride with benzyl alcohol is presented herein. The organic and inorganic species involved in the formation of the nanoparticles were studied by time‐dependent gas......‐scanning extended X‐ray absorption fine structure spectroscopy enabled the time‐dependent evolution of the starting compound, the intermediates and the product to be monitored over the full reaction period. The reaction starts with fast chlorine substitution and partial reduction during the dissolution...

  13. Anchoring Tri(8-QuinolinolatoIron Onto Sba-15 for Partial Oxidation of Benzyl Alcohol Using Water as the Solvent

    Directory of Open Access Journals (Sweden)

    Yang Xiaoyuan

    2014-09-01

    Full Text Available Tri(8-quinolinolatoiron complex immobilized onto SBA-15 catalyst has been synthesized through a stepwise procedure. The characterization results indicated that the BET surface area, total pore volume and average pore width decrease after stepwise modification of SBA-15, while the structure keeps intact. Catalytic tests showed that FeQ3-SBA-15 catalyzes the oxidation reaction well with 34.8% conversion of benzyl alcohol and 74.7% selectivity to benzaldehyde when water is used as the solvent after 1 h reaction. In addition, homogeneous catalyst tri(8-quinolinolatoiron exhibits very bad catalytic behavior using water as the solvent.

  14. A Comparative Study to Evaluate Myogenic Differentiation Potential of Human Chorion versus Umbilical Cord Blood-derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Bana, Nikoo; Sanooghi, Davood; Soleimani, Mansoureh; Hayati Roodbari, Nasim; Alavi Moghaddam, Sepideh; Joghataei, Mohammad Taghi; Sayahpour, Forough Azam; Faghihi, Faezeh

    2017-08-01

    Musculodegenerative diseases threaten the life of many patients in the world. Since drug administration is not efficient in regeneration of damaged tissues, stem cell therapy is considered as a good strategy to restore the lost cells. Since the efficiency of myogenic differentiation potential of human Chorion- derived Mesenchymal Stem Cells (C-MSCs) has not been addressed so far; we set out to evaluate myogenic differentiation property of these cells in comparison with Umbilical Cord Blood- derived Mesenchymal Stem Cells (UCB-MSCs) in the presence of 5-azacytidine. To do that, neonate placenta Umbilical Cord Blood were transferred to the lab. After characterization of the isolated cells using flowcytometry and multilineage differentiation capacity, the obtained Mesenchymal Stem Cells were cultured in DMEM/F12 supplemented with 2% FBS and 10μM of 5-azacytidine to induce myogenic differentiation. Real-time PCR and immunocytochemistry were used to assess the myogenic properties of the cells. Our data showed that C-MSCs and UCB-MSCs were spindle shape in morphology. They were positive for CD90, CD73 and CD44 antigens, and negative for hematopoietic markers. They also differentiated into osteoblast and adipoblast lineages. Real-time PCR results showed that the cells could express MyoD, desmin and α-MHC at the end of the first week (P<0.05). No significant upregulation was detected in the expression of GATA-4 in both groups. Immunocytochemical staining revealed the expression of Desmin, cTnT and α-MHC. Results showed that these cells are potent to differentiate into myoblast- like cells. An upregulation in the expression of some myogenic markers (desmin, α- MHC) was observed in C-MSCs in comparison with UCB-MSCs. Copyright © 2017. Published by Elsevier Ltd.

  15. Synthesis and evaluation of [{sup 14}C]-Labelled and fluorescent-Tagged paclitaxel derivatives as new biological probes

    Energy Technology Data Exchange (ETDEWEB)

    Rao, C.S.; Chu, J.-J.; Lai, Y.-K. [Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan (China); Liu, R.-S. [Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan (China)

    1998-11-01

    Our present report deals with the preparation of hitherto unreported 7-([carbonyl-{sup 14}C]-acetyl)paclitaxel 4 and two new bioactive 7-substituted fluorescent taxoids (FITC 9 and rhodamine 11), as well as evaluation towards their applications as biological probes. The results in this report demonstrate that (a) the new paclitaxel derivatives 4, 9, 11 could be prepared with good yields starting from paclitaxel; (b) the [{sup 14}C]acetylation step was found to be better by using [{sup 14}C]acetic anhydride rather than [{sup 14}C]sodium acetate; (c) the radiochemical purity of 4 was 96% and its specific activity was 48 mCi/mmol; (d) the cytotoxicity of 4 was close to that of paclitaxel whereas 9, 11 were far less active than paclitaxel, but these cytotoxic levels were good enough for their biological applications; (e) the drug-quantitation by flow cytometric analysis using 9 and 11 was proved to be equally efficient with respect to the radioactivity-based determination employing 4; (f) the intracellular fluorescence mapping by 9 and 11 was found to be effective and the microtubule network pattern was visible in both the cases; (g) the overall fluorescence imaging efficiency was better with 11 while the intensity of fluorescence was higher with 9; (h) staining of nucleolus was observed in fluorescence studies of both 9 and 11. Based on these results, the newly prepared paclitaxel derivatives can be considered as efficient biological probes and should find further use in relevant applications. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  16. Evaluation of single amino acid chelate derivatives and regioselective radiolabelling of a cyclic peptide for the urokinase plasminogen activator receptor

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Andrea F.; Lemon, Jennifer A. [McMaster Institute for Applied Radiation Sciences, McMaster University, ON, L8S 4M1 (Canada); Czorny, Shannon K. [McMaster Institute for Applied Radiation Sciences, McMaster University, ON, L8S 4M1 (Canada); Juravinski Cancer Centre, Hamilton, ON, L8V 5C2 (Canada); Singh, Gurmit [Juravinski Cancer Centre, Hamilton, ON, L8V 5C2 (Canada); Valliant, John F. [Department of Chemistry, McMaster University, Hamilton, ON, L8S 4M1 (Canada); Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON, L8S 4M1 (Canada)], E-mail: valliant@mcmaster.ca

    2009-11-15

    Introduction: The aim of this work was to investigate the relative radiolabelling kinetics and affinity of a series of ligands for the [{sup 99m}Tc(CO){sub 3}]{sup +} core, both in the absence and in the presence of competing donors. This information was used to select a suitable ligand for radiolabelling complex peptide-based targeting vectors in high yield under mild conditions. Methods: A series of {alpha}-N-Fmoc-protected lysine derivatives bearing two heterocyclic donor groups at the {epsilon}-amine (, 2-pyridyl; , quinolyl; , 6-methoxy-2-pyridyl; 1d, 2-thiazolyl; 1e, N-methylimidazolyl; , 3-pyridyl) were synthesized and labelled with {sup 99m}Tc. A resin-capture purification strategy for the separation of residual ligand from the radiolabelled product was also developed. The binding affinities of targeted peptides 4, 5a and 5b for uPAR were determined using flow cytometry. Results: Variable temperature radiolabelling reactions using - and [{sup 99m}Tc(CO){sub 3}]{sup +} revealed optimal kinetics and good selectivity for compounds and 1d; in the case of , 1d, and 1e, the labelling can be conducted at ambient temperature. The utility of this class of ligands was further demonstrated by the radiolabelling of a cyclic peptide that is known to target the serine protease receptor uPAR; essentially quantitative incorporation of {sup 99m}Tc occurred exclusively at the SAAC site, despite the presence of a His residue, and without disruption of the disulfide bond. Conclusion: A series of single amino acid chelate (SAAC) ligands have been evaluated for their ability to incorporate {sup 99m}Tc into peptides. The lead agent to emerge from this work is the thiazole SAAC derivative 1d which has demonstrated the ability to regioselectively label the widest range of peptides.

  17. Evaluation of hepatocyte-derived microRNA-122 for diagnosis of acute and chronic hepatitis of dogs

    Directory of Open Access Journals (Sweden)

    S. R. Eman

    2018-05-01

    Full Text Available Aim: This study was performed to evaluate the diagnostic value of hepatocyte-derived microRNA (miRNA-122 in acute and chronic hepatitis of dogs. Materials and Methods: A total of 26 dogs presented at Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Cairo University, 16 dogs out of 26 showing clinical signs of hepatic insufficiency were subjected to clinical, ultrasonographic, hematobiochemical and ultrasound-guided fine-needle biopsy for cytological and histopathological investigations. On the basis of these results, 7 dogs out of 16 dogs were found to be suffering from acute hepatitis and 9 dogs suffering from chronic hepatitis. 10 clinically healthy dogs were kept as control. Serum hepatocyte-derived miRNA-122 was analyzed by real-time quantitative polymerase chain reaction in all dogs. Results: The dogs suffering from acute hepatitis manifested jaundice, vomiting, and depression while dogs with chronic hepatitis manifested anorexia, abdominal distension, weight loss, and melena. Hematological parameters showed normocytic normochromic anemia and thrombocytopenia in both acute and chronic hepatitis groups. Alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, and total bilirubin were significantly higher than control values in acute hepatitis. In chronic hepatitis, total protein and albumin were significantly lower than control values with normal ALT, AST, ALP, and gamma-glutamyltransferase values. Ultrasonography revealed a diffuse decrease in hepatic echogenicity in acute hepatitis while the increase in hepatic echogenicity and anechoic ascetic fluid in chronic hepatitis. Cytology revealed hepatic vacuolar degeneration and histopathology revealed necrosis and apoptosis of hepatocyte in acute hepatitis while revealed massive fibrous tissue proliferation in hepatic parenchyma in chronic hepatitis. Serum miRNA-122 analysis, normalized for glyceraldehyde-3- phosphate dehydrogenase expression

  18. TOXICOLOGICAL EVALUATION OF REALISTIC EMISSIONS OF SOURCE AEROSOLS (TERESA): APPLICATION TO POWER PLANT-DERIVED PM2.5

    Energy Technology Data Exchange (ETDEWEB)

    Annette Rohr

    2006-03-01

    TERESA (Toxicological Evaluation of Realistic Emissions of Source Aerosols) involves exposing laboratory rats to realistic coal-fired power plant and mobile source emissions to help determine the relative toxicity of these PM sources. There are three coal-fired power plants in the TERESA program; this report describes the results of fieldwork conducted at the first plant, located in the Upper Midwest. The project was technically challenging by virtue of its novel design and requirement for the development of new techniques. By examining aged, atmospherically transformed aerosol derived from power plant stack emissions, we were able to evaluate the toxicity of PM derived from coal combustion in a manner that more accurately reflects the exposure of concern than existing methodologies. TERESA also involves assessment of actual plant emissions in a field setting--an important strength since it reduces the question of representativeness of emissions. A sampling system was developed and assembled to draw emissions from the stack; stack sampling conducted according to standard EPA protocol suggested that the sampled emissions are representative of those exiting the stack into the atmosphere. Two mobile laboratories were then outfitted for the study: (1) a chemical laboratory in which the atmospheric aging was conducted and which housed the bulk of the analytical equipment; and (2) a toxicological laboratory, which contained animal caging and the exposure apparatus. Animal exposures were carried out from May-November 2004 to a number of simulated atmospheric scenarios. Toxicological endpoints included (1) pulmonary function and breathing pattern; (2) bronchoalveolar lavage fluid cytological and biochemical analyses; (3) blood cytological analyses; (4) in vivo oxidative stress in heart and lung tissue; and (5) heart and lung histopathology. Results indicated no differences between exposed and control animals in any of the endpoints examined. Exposure concentrations for the

  19. 1-O-Acetyl-3,4,6-tri-O-benzyl-2-C-bromomethyl-2-deoxy-α-d-glucopyranose

    Directory of Open Access Journals (Sweden)

    Henok H. Kinfe

    2013-01-01

    Full Text Available In the title compound, C30H33BrO6, the pyranose ring adopts a chair conformation. Two of the O-benzyl phenyl rings lie almost perpendicular to C/C/C/O plane formed by the ring atoms not attached to these O-benzyl phenyl rings, and form dihedral angles of 85.1 (2 and 64.6 (2°, while the third O-benzyl phenyl ring is twisted so that it makes a dihedral angle 34.9 (2° to this C/C/C/O plane. This twist is ascribed to the formation of an S(8 loop stabilized by a weak intramolecular C—H...O hydrogen bond.

  20. Benzyl isothiocyanate causes FoxO1-mediated autophagic death in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Dong Xiao

    Full Text Available Benzyl isothiocyanate (BITC, a constituent of edible cruciferous vegetables, inhibits growth of breast cancer cells but the mechanisms underlying growth inhibitory effect of BITC are not fully understood. Here, we demonstrate that BITC treatment causes FoxO1-mediated autophagic death in cultured human breast cancer cells. The BITC-treated breast cancer cells (MDA-MB-231, MCF-7, MDA-MB-468, BT-474, and BRI-JM04 and MDA-MB-231 xenografts from BITC-treated mice exhibited several features characteristic of autophagy, including appearance of double-membrane vacuoles (transmission electron microscopy and acidic vesicular organelles (acridine orange staining, cleavage of microtubule-associated protein 1 light chain 3 (LC3, and/or suppression of p62 (p62/SQSTM1 or sequestosome 1 expression. On the other hand, a normal human mammary epithelial cell line (MCF-10A was resistant to BITC-induced autophagy. BITC-mediated inhibition of MDA-MB-231 and MCF-7 cell viability was partially but statistically significantly attenuated in the presence of autophagy inhibitors 3-methyl adenine and bafilomycin A1. Stable overexpression of Mn-superoxide dismutase, which was fully protective against apoptosis, conferred only partial protection against BITC-induced autophagy. BITC treatment decreased phosphorylation of mTOR and its downstream targets (P70s6k and 4E-BP1 in cultured MDA-MB-231 and MCF-7 cells and MDA-MB-231 xenografts, but activation of mTOR by transient overexpression of its positive regulator Rheb failed to confer protection against BITC-induced autophagy. Autophagy induction by BITC was associated with increased expression and acetylation of FoxO1. Furthermore, autophagy induction and cell growth inhibition resulting from BITC exposure were significantly attenuated by small interfering RNA knockdown of FoxO1. In conclusion, the present study provides novel insights into the molecular circuitry of BITC-induced cell death involving FoxO1-mediated autophagy.

  1. A novel mesoporous sulfated zirconium solid acid catalyst for Friedel-Crafts benzylation reaction

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Zhichao; Zhou, Jin; Zhao, Jinping; Liu, Dandan; Bi, Xu [School of Chemical Engineering, Shandong University of Technology, Zibo, 255049 (China); Chou, Lingjun, E-mail: ljchou@licp.cas.cn [State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, 730000 (China); Zhuo, Shuping, E-mail: zhuosp_academic@yahoo.com [School of Chemical Engineering, Shandong University of Technology, Zibo, 255049 (China)

    2017-07-31

    Highlights: • A novel mesoporous ZrO{sub 2}/SO{sub 4}{sup 2−} has been prepared via a facile one-pot EISA strategy. • The M-ZrO{sub 2}/SO{sub 4}{sup 2−} exhibited excellent textural and acidic properties. • The introduced S species were homogeneously dispersed in mesoporous skeleton. • The M-ZrO{sub 2}/SO{sub 4}{sup 2−} exhibited excellent catalytic performance and reusability. - Abstract: In this paper, a novel mesoporous sulfated zirconium (M-ZrO{sub 2}/SO{sub 4}{sup 2−}) has been gotten by one-pot evaporation-induced self-assembly (one-pot EISA) strategy. The SXRD, N{sub 2}-physisorption and TEM characterization techniques indicated that M-ZrO{sub 2}/SO{sub 4}{sup 2−} possessed distinct mesostructure with big specific surface area (133.5 m{sup 2} g{sup −1}), large pore volume (0.18 cm{sup 3} g{sup −1}) and narrow pore size distribution (4.90 nm). Moreover, the existing states and the influence in mesostructure of introduced S species were detailedly investigated by the XRD, N{sub 2}-physisorption, TEM, TG-DSC, FT-IR and XPS techniques and the results showed that the S species, which existed as the type of SO{sub 4}{sup 2−}, improved the textural properties of prepared materials. In addition, the NH{sub 3}-TPD and IR spectra of adsorbed pyridine indicated the existence of strong Brønsted and Lewis acid sites in M-ZrO{sub 2}/SO{sub 4}{sup 2−} even evacuated at 400 °C. Furthermore, the M-ZrO{sub 2}/SO{sub 4}{sup 2−} was used as a promise solid acid catalyst and displayed excellent catalytic performance and reusability in Friedel-Crafts benzylation reaction.

  2. The crystal structures of 3-O-benzyl-1,2-O-isopropylidene-5-O-methanesulfonyl-6-O-triphenylmethyl-α-d-glucofuranose and its azide displacement product

    Directory of Open Access Journals (Sweden)

    Zane Clarke

    2018-06-01

    Full Text Available The effect of different leaving groups on the substitution versus elimination outcomes with C-5 d-glucose derivatives was investigated. The stereochemical configurations of 3-O-benzyl-1,2-O-isopropylidene-5-O-methanesulfonyl-6-O-triphenylmethyl-α-d-glucofuranose, C36H38O8S (3 [systematic name: 1-[(3aR,5R,6S,6aR-6-benzyloxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl-2-(trityloxyethyl methanesulfonate], a stable intermediate, and 5-azido-3-O-benzyl-5-deoxy-1,2-O-isopropylidene-6-O-triphenylmethyl-β-l-idofuranose, C35H35N3O5 (4 [systematic name: (3aR,5S,6S,6aR-5-[1-azido-2-(trityloxyethyl]-6-benzyloxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole], a substitution product, were examined and the inversion of configuration for the azido group on C-5 in 4 was confirmed. The absolute structures of the molecules in the crystals of both compounds were confirmed by resonant scattering. In the crystal of 3, neighbouring molecules are linked by C—H...O hydrogen bonds, forming chains along the b-axis direction. The chains are linked by C—H...π interactions, forming layers parallel to the ab plane. In the crystal of 4, molecules are also linked by C—H...O hydrogen bonds, forming this time helices along the a-axis direction. The helices are linked by a number of C—H...π interactions, forming a supramolecular framework.

  3. Evaluation of The Antibacterial Effects of The New Benzothiazole and Tetrahydropyrimidine Derivatives against Streptococcus Iniae, Edwardsiella Tarda and Aeromonas Hydrophila as Some Zoonotic Bacterial Pathogens

    Directory of Open Access Journals (Sweden)

    Reza Aryan

    2016-09-01

    Full Text Available Background & Objective: The novel stronger antibacterial compounds such as the thiazole and pyrimidine derivatives are needed in order to remove the threat of bacterial antibiotic resistance in zoonotic aquatic bacterial pathogens. In this study, we evaluated the inhibitory effect of the new benzothiazole and tetrahydropyrimidine derivatives against three important zoonotic aquatic pathogens including Streptococcus iniae, Edwardsiella tarda and Aeromonas hydrophila. Material & Methods: Benzothiazole and tetrahydropyrimidine derivatives were synthesized and dissolved in DMSO with a concentration of 8129 μg/mL. Then, the disk diffusion and broth microdilution methods were applied to evaluate the antibacterial effects. Results were recorded as the minimum inhibitory concentration (MIC and the growth inhibition zone diameter. Results: The study showed that the two tetrahydropyrimidine derivatives had no inhibition effects on all of the studied bacteria. Moreover, no inhibitory effect was observed from the three banzothiazole derivatives against A. hydrophila. However, the benzothiazole derivatives showed significant inhibitory effect against S. iniae and E. tarda with MIC of 256-1024 µg/mL and the growth inhibition zone diameter of 4.3±0.3-18.2±0.1 mm. Conclusion: The antibacterial effect of the new banzothiazole derivatives was confirmed on S. iniae and E. tarda pathogens for the first time.  

  4. Effect of addition of butyl benzyl phthalate plasticizer and zinc oxide nanoparticles on mechanical properties of cellulose acetate butyrate/organoclay biocomposite

    Science.gov (United States)

    Putra, B. A. P.; Juwono, A. L.; Rochman, N. T.

    2017-07-01

    Plastics as packaging materials and coatings undergo increasing demands globally each year. This pose a serious problem to the environment due to its difficulty to degrade. One solution to addressing the problem of plastic wastes is the use of bioplastics. According to the European Organization Bioplastic, one of the biodegradable plastics is derivative of cellulose. To improve mechanical properties of bioplastic, biocomposites are made with the addition of certain additives and fillers. The aim of this study is to investigate the effect of butyl benzyl phthalate plasticizer (BBP) and ZnO nanoparticles addition on mechanical properties of cellulose acetate butyrate (CAB) / organoclay biocomposite. ZnO nanoparticles synthesized from commercial ZnO precursor by using sol-gel size reduction method. ZnO was dissolved in a solution of citric acid in the ratio 1:1 to 1:5 to form zinc citrate. Zinc citrate then decomposed by calcination at temperature of 600oC. ZnO nanoparticles with an average size of 44.4 nm is obtained at a ratio of 1: 2. The addition of ZnO nanoparticles and BBP plasticizer was varied to determine the effect on the mechanical properties of biocomposite. The addition of 10 - 15 %wt ZnO nanoparticles and 30 - 40 %wt BBP plasticizer was studied to determine the effect on the tensile strength, elongation, and modulus elasticity of the biocomposites. Biocomposite films were made by using solution casting method with acetone as solvent. The addition of plasticizer BBP and ZnO nanoparticles by 30% and 10% made biocomposite has a tensile strength of 2.223 MPa.

  5. Evaluation of microsatellite loci from libraries derived from the wild diploid 'Calcutta 4' and 'Ouro' banana cultivars.

    Science.gov (United States)

    Silva, P R O; Jesus, O N J; Creste, S; Figueira, A; Amorim, E P; Ferreira, C F

    2015-09-25

    Microsatellite markers have been widely used in the quantification of genetic variability and for genetic breeding in Musa spp. The objective of the present study was to evaluate the discriminatory power of microsatellite markers derived from 'Calcutta 4' and 'Ouro' genomic libraries, and to analyze the genetic variability among 30 banana accessions. Thirty-eight markers were used: 15 from the 'Ouro' library and 23 from the 'Calcutta 4' library. Genetic diversity was evaluated by considering SSR markers as both dominant markers because of the presence of triploid accessions, and co-dominant markers. For the dominant analysis, polymorphism information content (PIC) values for 44 polymorphic markers ranged from 0.063 to 0.533, with a mean value of 0.24. A dendrogram analysis separated the BGB-Banana accessions into 4 groups: the 'Ouro' and 'Muísa Tia' accessions were the most dissimilar (93% dissimilarity), while the most similar accessions were 'Pacovan' and 'Walha'. The mean genetic distance between samples was 0.74. For the analysis considering SSR markers as co-dominants, using only diploid accessions, two groups were separated based on their genome contents (A and B). The PIC values for the markers from the 'Calcutta 4' library varied from 0.4836 to 0.7886, whereas those from the 'Ouro' library ranged from 0.3800 to 0.7521. Given the high PIC values, the markers from both the libraries showed high discriminatory power, and can therefore be widely applied for analysis of genetic diversity, population structures, and linkage mapping in Musa spp.

  6. Evaluation of the photocatalytic ability of a sol-gel-derived MgO-ZrO2 oxide material

    Directory of Open Access Journals (Sweden)

    Ciesielczyk Filip

    2017-02-01

    Full Text Available This paper deals with the synthesis and characterization of a novel group of potential photocatalysts, based on sol-gel-derived MgO-ZrO2 oxide material. The material was synthesized in a typical sol-gel system using organic precursors of magnesia and zirconia, ammonia as a promoter of hydrolysis and methanol as a solvent. All materials were thoroughly analyzed, including morphology and particle sizes, chemical composition, identification of characteristic functional groups, porous structure parameters and crystalline structure. The proposed methodology of synthesis resulted in obtaining pure MgO-ZrO2 oxide material with micrometric-sized particles and a relatively high surface area. The samples underwent an additional calcination process which led to the crystalline phase of zirconia being formed. The key element of the study was the evaluation of the effectiveness of decomposition of C.I. Basic Blue 9 dye. It was shown that the calcined materials exhibit both satisfactory adsorption and photocatalytic activity with respect to the decomposition of a selected model organic impurity. Total dye removal varied in the range of 50-70%, and was strongly dependent on process parameters such as quantity of photocatalyst, time of irradiation, and the addition of promoters.

  7. Synthesis, characterization and pharmacological evaluation of different 1,3,4-oxadiazole and acetamide derivatives of ethyl nipecotate

    Directory of Open Access Journals (Sweden)

    Khadija Nafeesa

    2017-12-01

    Full Text Available A new series of N-substituted derivatives of 2-[(5-{1-[(4-chlorophenylsulfonyl]-3-piperidinyl}-1,3,4-oxadiazol-2-ylsulfanyl]acetamide (6a-w has been designed and synthesized with multifunctional moieties. The synthesized compounds were evaluated for their antibacterial and anti-enzymatic potential supported by % hemolytic activity. The synthesized compound 5-(1-(4-chlorophenylsulfonyl-3-piperidinyl-1,3,4-oxadiazole-2-thiol (3 was stirred with synthesized electrophiles as N-aryl/alkyl/aralkyl-2-bromoacetamide (5a-w in an aprotic solvent under basic conditions to acquire the target molecules, 6a-w. The spectral analytical techniques of IR, EI-MS, 1H NMR and 13C-NMR were utilized for structural elucidation of synthesized molecules. The antibacterial screening against certain bacterial strains of gram-negative and gram-positive bacteria rendered compound 6i as good inhibitor of gram-negative bacterial strains. The enzyme inhibition revealed low potential against lipoxygenase (LOX enzyme. The hemolytic study provided valuable information about cytotoxic behavior of synthesized molecules. Keywords: 1,3,4-Oxadiazole, Acetamide, Antibacterial activity, Hemolytic activity, Lipoxygenase inhibition

  8. Synthesis and evaluation of a class of 1,4,7-triazacyclononane derivatives as iron depletion antitumor agents.

    Science.gov (United States)

    Wang, Sheng; Gai, Yongkang; Zhang, Shasha; Ke, Lei; Ma, Xiang; Xiang, Guangya

    2018-01-15

    Iron depletion has been confirmed as an efficient strategy for cancer treatment. In the current study, a series of 1,4,7-triazacyclononane derivatives HE-NO2A, HP-NO2A and NE2P2A, as well as the bifunctional chelators p-NO 2 -PhPr-NE3TA and p-NH 2 -PhPr-NE3TA were synthesized and evaluated as iron-depleting agents for the potential anti-cancer therapy against human hepatocellular carcinoma. The cytotoxicity of these chelators was measured using hepatocellular cancer cells and compared with the clinically available iron depletion agent DFO and the universal metal chelator DTPA. All these 1,4,7-triazacyclononane-based chelators exhibited much stronger antiproliferative activity than DFO and DTPA. Among them, chelators with phenylpropyl side chains, represented by p-NO 2 -PhPr-NE3TA and p-NH 2 -PhPr-NE3TA, displayed the highest antiproliferative activity against HepG2 cells. Hence, these compounds are attractive candidates for the advanced study as iron depletion agents for the potential anti-cancer therapy, and could be further in conjugation with a targeting moiety for the future development in targeted iron depletion therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Synthesis and biological evaluation of 4-(2-fluorophenoxy)-3,3'-bipyridine derivatives as potential c-met inhibitors.

    Science.gov (United States)

    Zhao, Sijia; Zhang, Yu; Zhou, Hongyang; Xi, Shuancheng; Zou, Bin; Bao, Guanglong; Wang, Limei; Wang, Jiao; Zeng, Tianfang; Gong, Ping; Zhai, Xin

    2016-09-14

    Six series of novel 4-(2-fluorophenoxy)-3,3'-bipyridine derivatives conjugated with aza-aryl formamide/amine scaffords were designed and synthesized through a structure-based molecular hybridization approach. The target compounds were evaluated for c-Met kinase inhibitory activities and cytotoxicity against four cancer cell lines (HT-29, A549, MKN-45 and MDA-MB-231) in vitro. Most compounds exhibited moderate to excellent potency, and the most promising candidate 26c (c-Met kinase IC50 = 8.2 nM) showed a 4.7-fold increase in cytotoxicity against c-Met-addicted MKN-45 cell line in vitro (IC50 = 3 nM), superior to that of Foretinib (IC50 = 23 nM). The preliminary structure-activity relationship indicated that a 1H-benzo [e] [1,3,4]thiadiazine-3-carboxamide-4,4-dioxide moiety as linker contributed to the antitumor potency. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Evaluation of left ventricular function by tissue Doppler and speckle-derived strain rate echocardiography after percutaneous ductus closure.

    Science.gov (United States)

    Amoogzar, Hamid; Shakiba, Ali Mohammad; Derakhshan, Dorna; Ajami, Gholamhossein; Cheriki, Sirous; Borzouee, Mohammad; Edraki, Mohammad Reza; Mehdizadegan, Nima

    2015-01-01

    The aim of this study was to evaluate the left ventricular systolic and diastolic function before and after transcatheter percutaneous patent ductus arteriosus (PDA) closure. 21 children (age >6 months old) diagnosed with hemodynamically significant PDA underwent percutaneous PDA closure. Conventional, Doppler and tissue Doppler imaging and speckled-derived strain rate echocardiography were done at pre-closure, 1 day (early) and 1 month (late) post-closure. Mean age of the patients (female/male: 1.3) was 17.54 ± 24.7 months with the mean PDA diameter of 3.6 ± 0.8 mm. Systolic measures (ejection fraction, shortening fraction) reduced significantly early after PDA closure (P closure status. Early and late diastolic flow velocities of mitral (E M and A M) reduced considerably in early and late post-closure time (P closure. After 1 month, E'M increased considerably. (P = 0.01) but E'M/A'M had an insignificant rise (P > 0.05). E M/E'M ratio did not change in early post-closure but it had a considerable reduction in the subsequent month compared with the pre- and early post-closure (P closure (P closure causes a significant decrease in left ventricular performance early after PDA closure which recovers completely within 1 month. Also PDA size can affect post-closure left ventricular function.

  11. Clinical and histologic evaluation of non-surgical periodontal therapy with enamel matrix derivative: a report of four cases.

    Science.gov (United States)

    Mellonig, James T; Valderrama, Pilar; Gregory, Holly J; Cochran, David L

    2009-09-01

    Enamel matrix derivative (EMD) is a composite of proteins that was demonstrated histologically to work as an adjunct to periodontal regenerative surgical therapy. The purpose of this study was to evaluate the clinical and histologic effects of EMD as an adjunct to scaling and root planing. Four patients with severe chronic periodontitis and scheduled to receive complete dentures were accrued. Probing depth and clinical attachment levels were obtained. Unlimited time was allowed for hand and ultrasonic instrumentation. A notch was placed in the root >or=1 to 2 mm from the apical extent of root planing. EMD was inserted into the pocket, and a periodontal dressing was placed. Patients were seen every 2 weeks for plaque control. At 6 months post-treatment, soft tissue measurements were repeated, and the teeth were removed en bloc and prepared for histomorphologic analysis. Probing depth reduction and clinical attachment level gain were obtained in three-fourths of the specimens. Three of the four specimens analyzed histologically demonstrated new cementum, bone, periodontal ligament, and connective tissue attachment coronal to the notch. In one specimen, the gingival margin had receded below the notch. The results were unexpected and may represent an aberration. However, the substantial reduction in deep probing depths and clinical attachment level gain in three of four specimens, in addition to the histologic findings of new cementum, new bone, a new periodontal ligament, and a new connective tissue attachment, suggest that EMD may be useful as an adjunct to scaling and root planing in single-rooted teeth.

  12. A Novel Strategy Towards the Asymmetric Synthesis of Orthogonally Funtionalised 2-N-Benzyl-N-α-methylbenzylamino- 5-carboxymethyl-cyclopentane-1-carboxylic acid.

    Directory of Open Access Journals (Sweden)

    Julio G. Urones

    2004-04-01

    Full Text Available The asymmetric synthesis of the orthogonally funtionalised compounds tert-butyl 2-N-benzyl-N-α-methylbenzylamino-5-methoxycarbonylmethylcyclopentane- 1-carboxylate and methyl 2-N-benzyl-N-α-methylbenzylamino-5–carboxymethylcyclo- pentane-1-carboxylate by a domino reaction of tert-butyl methyl (E,E-octa-2,6- diendioate with lithium N-α-methylbenzyl-N-benzylamide initiated by a Michael addition, subsequent 5-exo-trig intramolecular cyclisation and posterior selective hydrolysis with trifluoroacetic acid is reported.

  13. Effective oxidation of benzylic and alkane C-H bonds catalyzed by sodium o-iodobenzenesulfonate with Oxone as a terminal oxidant under phase-transfer conditions.

    Science.gov (United States)

    Cui, Li-Qian; Liu, Kai; Zhang, Chi

    2011-04-07

    Catalytic oxidation of benzylic C-H bonds could be efficiently realized using IBS as a catalyst which was generated in situ from the oxidation of sodium 2-iodobenzenesulfonate (1b) by Oxone in the presence of a phase-transfer catalyst, tetra-n-butylammonium hydrogen sulfate, in anhydrous acetonitrile at 60 °C. Various alkylbenzenes, including toluenes and ethylbenzenes, several oxygen-containing functionalities substituted alkylbenzenes, and a cyclic benzyl ether could be efficiently oxidized. And, the same reagent system of cat. 1b/Oxone/cat. n-Bu(4)NHSO(4) could be applied to the effective oxidation of alkanes as well.

  14. Primary and secondary kinetic deuterium isotope effects and transition-state structures for benzylic chlorination and bromination of toluene

    International Nuclear Information System (INIS)

    Hanzlik, R.P.; Schaefer, A.R.; Moon, J.B.; Judson, C.M.

    1987-01-01

    As a chemical model for benzylic hydroxylation effects by cytochrome P-450 enzymes, the chlorination of PhCH 3 , PhCH 2 D, PhCHD 2 , and PhCD 3 in a two-phase system of hypochlorite/CH 2 Cl 2 with a phase-transfer catalyst has been investigated. On the basis of the deuterium content of the product benzyl chlorides, relative rate constants were deduced for all possible H- and D-abstractions with these substrates. From this the primary (P) and secondary (S) KDIEs were found to be 5.90 +/- 0.41 and 1.03 +/- 0.02, respectively, and the rule of the geometric mean was found to be closely obeyed. For the analogous bromination of toluene by N-bromosuccinimide in CCl 4 , P and S were 6.37 +/- 0.43 and 1.05 +/- 0.01. The transition states of these processes must therefore involve extensive C-H bond breaking but relatively little rehybridization toward planarity at the reacting carbon

  15. Synthesis, growth and characterization of organic nonlinear optical material: N-benzyl-2-methyl-4-nitroaniline (BNA)

    Science.gov (United States)

    Kalaivanan, R.; Srinivasan, K.

    2017-05-01

    Synthesis of the organic nonlinear optical compound N-benzyl-2-methyl-4-nitroaniline (BNA) was carried out in a newer chemical environment using the mixture of benzyl chloride and 2-methl-4-nitroaniline by a preferred laboratory synthesis process. The synthesized BNA compound was separated by column chromatography (CC) with low pressure silica gell using petrollium benzine and purity of the separated resultant product was confirmed by thin layer chromatography (TLC). Further, the material was recrystallized atleast four times in methanol and the highly purified BNA was used for the growth of single crystals from solutions with selected solvents by slow evaporation method at room temperature. Single crystals having natural growth morphology were harvested and their different growth faces were identified by optical goniometry. The grown crystals were subjected to different characterization techniques such as powder x-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and UV-vis-Near IR spectroscopy. Further, the second harmonic generation (SHG) efficiency of the grown BNA crystal was studied by Kurtz and Perry powder technique using Nd:YAG laser as fundamental source and found to be twice that of inorganic standard KDP.

  16. Evaluation of amniotic mesenchymal cell derivatives on cytokine production in equine alveolar macrophages: an in vitro approach to lung inflammation.

    Science.gov (United States)

    Zucca, Enrica; Corsini, Emanuela; Galbiati, Valentina; Lange-Consiglio, Anna; Ferrucci, Francesco

    2016-09-20

    Data obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. Recently, new therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. The aim of this study was to investigate the immunomodulatory effects of equine amniotic mesenchymal cell derivatives on lipopolysaccharide (LPS)-induced cytokine production in equine alveolar macrophages, which may be beneficial in lung inflammatory disorders such as recurrent airway obstruction (RAO) in horses. RAO shares many features with human asthma, including an increased number of cells expressing mRNA for interleukin (IL)-4 and IL-5 and a decreased expression of IFN-γ in bronchoalveolar lavage fluid (BALF) of affected horses. The release of TNF-α, IL-6, and TGF-β1 at different time points (1, 24, 48, and 72 h) was measured in equine alveolar macrophages stimulated or not with LPS (10 and 100 ng/mL) in the presence or absence of 10 % CM or 50 × 10(6) MVs/mL. Cytokines were measured using commercially available ELISA kits. For multiple comparisons, analysis of variance was used with Tukey post-hoc test. Differences were considered significant at p ≤ 0.05. Significant modulatory effects of CM on LPS-induced TNF-α release at 24 h, and of both CM and MVs on TNF-α release at 48 h were observed. A trend toward a modulatory effect of both CM and MVs on the release of TGF-β and possibly IL-6 was visible over time. Results support the potential use of CM and MVs in lung regenerative medicine, especially in situations in which TGF-β may be detrimental, such as respiratory allergy. Further studies should evaluate the potential clinical applications of CM and MVs in equine lung diseases, such as RAO and other inflammatory disorders.

  17. Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R

    International Nuclear Information System (INIS)

    Atsmon, Jacob; Brill-Almon, Einat; Nadri-Shay, Carmit; Chertkoff, Raul; Alon, Sari; Shaikevich, Dimitri; Volokhov, Inna; Haim, Kirsten Y.; Bartfeld, Daniel; Shulman, Avidor; Ruderfer, Ilya; Ben-Moshe, Tehila; Shilovitzky, Orit; Soreq, Hermona; Shaaltiel, Yoseph

    2015-01-01

    PRX-105 is a plant-derived recombinant version of the human ‘read-through’ acetylcholinesterase splice variant (AChE-R). Its active site structure is similar to that of the synaptic variant, and it displays the same affinity towards organophosphorus (OP) compounds. As such, PRX-105 may serve as a bio-scavenger for OP pesticides and chemical warfare agents. To assess its potential use in prophylaxis and treatment of OP poisoning we conducted several preliminary tests, reported in this paper. Intravenous (IV) PRX-105 was administered to mice either before or after exposure to an OP toxin. All mice who received an IV dose of 50 nmol/kg PRX-105, 2 min before being exposed to 1.33 × LD 50 and 1.5 × LD 50 of toxin and 10 min after exposure to 1.5 × LD 50 survived. The pharmacokinetic and toxicity profiles of PRX-105 were evaluated in mice and mini-pigs. Following single and multiple IV doses (50 to 200 mg/kg) no deaths occurred and no significant laboratory and histopathological changes were observed. The overall elimination half-life (t ½ ) in mice was 994 (± 173) min. Additionally, a first-in-human study, to assess the safety, tolerability and pharmacokinetics of the compound, was conducted in healthy volunteers. The t ½ in humans was substantially longer than in mice (average 26.7 h). Despite the small number of animals and human subjects who were assessed, the fact that PRX-105 exerts a protective and therapeutic effect following exposure to lethal doses of OP, its favorable safety profile and its relatively long half-life, renders it a promising candidate for treatment and prophylaxis against OP poisoning and warrants further investigation. - Highlights: • PRX-105 is a PEGylated plant-derived recombinant human acetylcholinesterase-R. • PRX-105 is a promising bio-scavenger for organophosphorous toxins at lethal doses. • PRX-105 was shown to protect animals both prophylactically and post-poisoning. • First-in-human study exhibited its safety

  18. Molecular imaging of alkylguanine-DNA alkyltransferase: further evaluation of radioiodinated derivatives of O {sup 6}-benzylguanine

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, Sriram [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R. [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Friedman, Henry [Department of Surgery, Duke University Medical Center, Durham, NC 27710 (United States); Department of Pediatrics, Duke University Medical Center, Durham, NC 27710 (United States); Vaidyanathan, Ganesan [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)]. E-mail: ganesan.v@duke.edu

    2006-04-15

    Purpose: An inverse correlation has been established between tumor levels of the DNA repair protein alkylguanine-DNA alkyltransferase (AGT) and a positive outcome after alkylator chemotherapy. Quantitative imaging of AGT could provide important information for patient-specific cancer treatment. Several radiolabeled analogues of O {sup 6}-benzylguanine (BG), a potent AGT inactivator, have been developed and shown to be capable of labeling pure AGT protein. Herein, two of these analogues - O {sup 6}-3-[*I]iodobenzylguanine ([*I]IBG) and O {sup 6}-3-[*I]iodobenzyl-2'-deoxyguanosine ([*I]IBdG) - were further evaluated in two murine xenograft models. (AcO){sub 2}-[{sup 131}I]IBdG, a peracetylated derivative of IBdG, also was investigated as an alternative agent. Methods: Several biodistribution studies of radioiodinated IBG and IBdG were performed in TE-671 human rhabdomyosarcoma and DAOY human medulloblastoma murine xenograft models. Mice were treated with BG or its nucleoside analogue dBG to deplete the tumor AGT content. The effect of unlabeled IBG and that of 7,8-benzoflavone (BF), an inhibitor of the cytochrome P-450 isozyme CYP1A2, on the tumor uptake of the tracers was determined. The uptake of (AcO){sub 2}-[{sup 131}I]IBdG along with that of [{sup 125}I]IBdG in DAOY cells in vitro was determined in the presence and absence of a nucleoside transporter inhibitor, dipyridamole. Results: Pretreatment of mice either with BG or dBG failed to reduce tumor levels of [*I]IBG or [*I]IBdG even though such treatments completely depleted tumor AGT content. Treatment of mice with BF increased tumor uptake of [{sup 125}I]IBG by 56%; however, differentiation of tumors with and without AGT still was not possible. (AcO){sub 2}-[{sup 131}I]IBdG, a peracetylated derivative of IBdG, had a higher uptake in vitro in DAOY tumor cells. However, its uptake, like that of [{sup 125}I]IBdG, was blocked by dipyridamole. Conclusions: Taken together, these results suggest that labeled

  19. Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R

    Energy Technology Data Exchange (ETDEWEB)

    Atsmon, Jacob [Clinical Research Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University (Israel); Brill-Almon, Einat; Nadri-Shay, Carmit; Chertkoff, Raul; Alon, Sari [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Shaikevich, Dimitri; Volokhov, Inna; Haim, Kirsten Y. [Clinical Research Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University (Israel); Bartfeld, Daniel [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Shulman, Avidor, E-mail: avidors@protalix.com [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Ruderfer, Ilya; Ben-Moshe, Tehila; Shilovitzky, Orit [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Soreq, Hermona [Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem (Israel); Shaaltiel, Yoseph [Protalix Biotherapeutics, Science Park, Carmiel (Israel)

    2015-09-15

    PRX-105 is a plant-derived recombinant version of the human ‘read-through’ acetylcholinesterase splice variant (AChE-R). Its active site structure is similar to that of the synaptic variant, and it displays the same affinity towards organophosphorus (OP) compounds. As such, PRX-105 may serve as a bio-scavenger for OP pesticides and chemical warfare agents. To assess its potential use in prophylaxis and treatment of OP poisoning we conducted several preliminary tests, reported in this paper. Intravenous (IV) PRX-105 was administered to mice either before or after exposure to an OP toxin. All mice who received an IV dose of 50 nmol/kg PRX-105, 2 min before being exposed to 1.33 × LD{sub 50} and 1.5 × LD{sub 50} of toxin and 10 min after exposure to 1.5 × LD{sub 50} survived. The pharmacokinetic and toxicity profiles of PRX-105 were evaluated in mice and mini-pigs. Following single and multiple IV doses (50 to 200 mg/kg) no deaths occurred and no significant laboratory and histopathological changes were observed. The overall elimination half-life (t{sub ½}) in mice was 994 (± 173) min. Additionally, a first-in-human study, to assess the safety, tolerability and pharmacokinetics of the compound, was conducted in healthy volunteers. The t{sub ½} in humans was substantially longer than in mice (average 26.7 h). Despite the small number of animals and human subjects who were assessed, the fact that PRX-105 exerts a protective and therapeutic effect following exposure to lethal doses of OP, its favorable safety profile and its relatively long half-life, renders it a promising candidate for treatment and prophylaxis against OP poisoning and warrants further investigation. - Highlights: • PRX-105 is a PEGylated plant-derived recombinant human acetylcholinesterase-R. • PRX-105 is a promising bio-scavenger for organophosphorous toxins at lethal doses. • PRX-105 was shown to protect animals both prophylactically and post-poisoning. • First-in-human study

  20. Derivation of parameters necessary for the evaluation of performance of sites for deep geological repositories with particular reference to bedded salt, Livermore, California. Volume I. Main text

    International Nuclear Information System (INIS)

    Ashby, J.P.; Rawlings, G.E.; Soto, C.A.; Wood, D.F.; Chorley, D.W.

    1979-12-01

    A survey of parameters to be considered in the evaluation of sites for deep geologic nuclear waste repositories is presented. As yet, no comprehensive site selection procedure or performance evaluation approach has been adopted. A basis is provided for the development of parameters by discussing both site selection and performance evaluation. Three major groups of parameters are considered in this report: geologic, mining/rock mechanics, and hydrogeologic. For each type, the role of the parameter in the evaluation of repository sites is discussed. The derivation of the parameter by measurement, correlation, inference, or other method is discussed. Geologic parameters define the framework of the repository site and can be used in development of conceptual models and the prediction of long-term performance. Methods for deriving geological parameters include mapping, surveying, drilling, geophysical investigation, and historical and regional analysis. Rock mechanics/mining parameters are essential for the prediction of short-term performance and the development of initial conditions for modeling of long-term performance. Rock mechanics/mapping parameters can be derived by field or laboratory investigation, correlation, and theoretically or empirically based inference. Hydrogeologic parameters are the most important for assessment of long-term radionuclide confinement, since transport throughout the regional hydrogeologic system is the most likely mode of radionuclide escape from geologic repositories. Hydrogeologic parameters can be derived by hydrogeologic mapping and interpretation, hydrogeologic system modeling, field measurements, and lab tests. Procedures used in determination and statistical evaluation of geologic and rock mechanics parameters are discussed