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Sample records for benzyl derivatives evaluated

  1. Synthesis and biological evaluation of novel benzyl-substituted (S)-phenylalanine derivatives as potent dipeptidyl peptidase 4 inhibitors.

    Science.gov (United States)

    Liu, Yang; Si, Meimei; Tang, Li; Shangguan, Shihao; Wu, Haoshu; Li, Jia; Wu, Peng; Ma, Xiaodong; Liu, Tao; Hu, Yongzhou

    2013-09-15

    A series of novel benzyl-substituted (S)-phenylalanine derivatives were synthesized and evaluated for their dipeptidyl peptidase 4 (DPP-4) inhibitory activity and selectivity. It was found that most synthesized target compounds were potent DPP-4 inhibitors with IC50 values in 3.79-25.52 nM, which were significantly superior to that of the marketed drug sitagliptin. Furthermore, the 4-fluorobenzyl substituted phenylalanine derivative 6g not only displayed the potent DPP-4 inhibition with an IC50 value of 3.79 nM, but also showed better selectivity against DPP-4 over other related enzymes including DPP-7, DPP-8, and DPP-9. In an oral glucose tolerance test (OGTT) in normal Sprague Dawley rats, compound 6g reduced blood glucose excursion in a dose-dependent manner.

  2. (E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety as potential immunosuppressive agents: Design, synthesis, molecular docking and biological evaluation.

    Science.gov (United States)

    Lv, Xian-Hai; Li, Qing-Shan; Ren, Zi-Li; Chu, Ming-Jie; Sun, Jian; Zhang, Xin; Xing, Man; Zhu, Hai-Liang; Cao, Hai-Qun

    2016-01-27

    A series of novel (E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety were firstly synthesized and their immunosuppressive activities were evaluated. Among all the compounds, 4n exhibited the most potent inhibitory activity (IC50 = 1.18 μM for lymph node cells and IC50 = 0.28 μM for PI3Kγ), which was comparable to that of positive control. Moreover, selected compounds were tested for their inhibitory activities against IL-6 released in ConA-simulated mouse lymph node cells, 4n exhibited the most potent inhibitory ability. Furthermore, in order to study the preliminary mechanism of the compounds with potent inhibitory activity, the RT-PCR experiment was performed to assay the effect of selected compounds on mRNA expression of IL-6. Among them, compound 4n strongly inhibited the expression of IL-6 mRNA.

  3. Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives

    Science.gov (United States)

    Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

    2016-01-01

    Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-(N,N-dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a–b) as well as chalcone derivatives (3a–c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans. PMID:27877017

  4. Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives

    Directory of Open Access Journals (Sweden)

    Shakhatreh MA

    2016-11-01

    Full Text Available Muhamad Ali K Shakhatreh,1 Mousa L Al-Smadi,2 Omar F Khabour,1,3 Fatima A Shuaibu,1 Emad I Hussein,4 Karem H Alzoubi51Department of Medical Laboratory Sciences, 2Department of Applied Chemical Sciences, Jordan University of Science and Technology, Irbid, Jordan; 3Faculty of Applied Medical Sciences, Taibah University, Madina, Saudi Arabia; 4Department of Biological Sciences, Yarmouk University, 5Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan Abstract: Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-(N,N-dimethylaminobenzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a–b as well as chalcone derivatives (3a–c showed no activity against all the tested strains except for ketone (2c, which showed moderate activity against

  5. Azido-iodo-N-benzyl derivatives of threo-methylphenidate (Ritalin, Concerta): Rational design, synthesis, pharmacological evaluation, and dopamine transporter photoaffinity labeling.

    Science.gov (United States)

    Lapinsky, David J; Velagaleti, Ranganadh; Yarravarapu, Nageswari; Liu, Yi; Huang, Yurong; Surratt, Christopher K; Lever, John R; Foster, James D; Acharya, Rejwi; Vaughan, Roxanne A; Deutsch, Howard M

    2011-01-01

    In contrast to tropane-based compounds such as benztropine and cocaine, non-tropane-based photoaffinity ligands for the dopamine transporter (DAT) are relatively unexplored. Towards addressing this knowledge gap, ligands were synthesized in which the piperidine nitrogen of 3- and 4-iodomethylphenidate was substituted with a benzyl group bearing a photoreactive azide. Analog (±)-3a demonstrated modest DAT affinity and a radioiodinated version was shown to bind covalently to rat striatal DAT and hDAT expressed in cultured cells. Co-incubation of (±)-3a with nonradioactive d-(+)-methylphenidate or (-)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane (β-CFT, WIN-35,428, a cocaine analog) blocked DAT labeling. Compound (±)-3a represents the first successful example of a DAT photoaffinity ligand based on the methylphenidate scaffold. Such ligands are expected to assist in mapping non-tropane ligand-binding pockets within plasma membrane monoamine transporters.

  6. Synthesis and evaluation of the cytotoxic activity of novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives in myeloid and lymphoid leukemia cell lines.

    Science.gov (United States)

    Desplat, Vanessa; Vincenzi, Marian; Lucas, Romain; Moreau, Stéphane; Savrimoutou, Solène; Pinaud, Noël; Lesbordes, Jordi; Peyrilles, Elodie; Marchivie, Mathieu; Routier, Sylvain; Sonnet, Pascal; Rossi, Filomena; Ronga, Luisa; Guillon, Jean

    2016-05-01

    Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resistant cases. Among heterocyclic compounds that attracted a lot of attention because of its wide spread biological activities, the pyrrolo[1,2-a]quinoxaline heterocyclic framework has been identified as interesting scaffolds for antiproliferative activity against various human cancer cell lines. In the present study, novel ethyl 4-[4-(4-substitutedpiperidin-1-yl)]benzyl-phenylpyrrolo[1,2-a]quinoxaline-carboxylate derivatives 1a-l have been designed and synthesized. Their cytotoxicities were evaluated against five different leukemia cell lines, including Jurkat and U266 (lymphoid cell lines), and K562, U937, HL60 (myeloid cell lines), as well as normal human peripheral blood mononuclear cells (PBMNCs). Then, apoptosis study was performed with the more interesting compounds. The new pyrrolo[1,2-a]quinoxaline series showed promising cytotoxic potential against all leukemia cell lines tested, and some compounds showed better results than the reference compound A6730. Some compounds, such as 1a, 1e, 1g and 1h are promising because of their high activity against leukemia and their low activity against normal hematopoietic cells. Structure-activity relationships of these new synthetic compounds 1a-l are here also discussed.

  7. Multichromic polymers of benzotriazole derivatives: Effect of benzyl substitution

    Energy Technology Data Exchange (ETDEWEB)

    Yigitsoy, Basak [Department of Chemistry, Middle East Technical University, 06531 Ankara (Turkey); Abdul Karim, S.M. [Department of Arts and Sciences, Ahsanullah University of Science and Technology, Dhaka 1208 (Bangladesh); Balan, Abidin; Baran, Derya [Department of Chemistry, Middle East Technical University, 06531 Ankara (Turkey); Toppare, Levent, E-mail: toppare@metu.edu.t [Department of Chemistry, Middle East Technical University, 06531 Ankara (Turkey); Department of Biotechnology, Middle East Technical University, 06531 Ankara (Turkey); Department of Polymer Science and Technology, Middle East Technical University, 06531 Ankara (Turkey)

    2011-02-01

    Two electroactive monomers 1-benzyl-4,7-di(thiophen-2-yl))-2H-benzo[d][1,2,3]triazole (BBTA) and 2-benzyl-4,7-di(thiophen-2-yl))-2H-benzo[d][1,2,3]triazole (BBTS) were synthesized with satisfactory yields. The effect of substitution site on electrochemical and optical properties was investigated with cyclic voltammetry and spectroelectrochemical studies. Results showed that position of pendant group alters the electronic structure of the resulting polymer causing different optical and electrochemical behaviors. Symmetrically positioned benzyl unit on benzotriazole moiety resulted in a neutral state red polymer, PBBTS, having multi-colored property in its different oxidized and reduced states. Its analogue PBBTA exhibited maximum absorption at 390 nm in its neutral state and also revealed multicolored electrochromic property upon stepwise oxidation. Very different optical band gap values were calculated: 1.55 eV and 2.25 eV for PBBTS and PBBTA, respectively.

  8. Synthesis and biological activity of some new 1-benzyl and 1-benzoyl-3-heterocyclic indole derivatives.

    Science.gov (United States)

    El-Sawy, Eslam Reda; Bassyouni, Fatma A; Abu-Bakr, Sherifa H; Rady, Hanaa M; Abdlla, Mohamed M

    2010-03-01

    Starting from 1-benzyl- (2a) and 1-benzoyl-3-bromoacetyl indoles (2b) new heterocyclic, 2-thioxoimidazolidine (4a, b), imidazolidine-2,4-dione (5a, b), pyrano(2,3-d)imida-zole (8a, b and 9a, b), 2-substituted quinoxaline (11a, b-17a, b) and triazolo(4,3-a)quinoxaline derivatives (18a, b and 19a, b) were synthesized and evaluated for their antimicrobial and anticancer activities. Antimicrobial activity screening performed with concentrations of 0.88, 0.44 and 0.22 microg mm(-2) showed that 3-(1-substituted indol-3-yl)quinoxalin-2(1H)ones (11a, b) and 2-(4-methyl piperazin-1-yl)-3-(1-substituted indol-3-yl) quinoxalines (15a, b) were the most active of all the tested compounds towards P. aeruginosa, B. cereus and S. aureus compared to the reference drugs cefotaxime and piperacillin, while 2-chloro-3-(1-substituted indol-3-yl)quinoxalines (12a, b) were the most active against C. albicans compared to the reference drug nystatin. On the other hand, 2-chloro-3-(1-benzyl indol-3-yl) quinoxaline 12a display potent efficacy against ovarian cancer xenografts in nude mice with tumor growth suppression of 100.0 +/- 0.3 %.

  9. Structure-activity relationship of dopaminergic halogenated 1-benzyl-tetrahydroisoquinoline derivatives.

    Science.gov (United States)

    El Aouad, Noureddine; Berenguer, Inmaculada; Romero, Vanessa; Marín, Paloma; Serrano, Angel; Andujar, Sebastián; Suvire, Fernando; Bermejo, Almudena; Ivorra, M Dolores; Enriz, Ricardo D; Cabedo, Nuria; Cortes, Diego

    2009-11-01

    Two series of halogenated 1-benzyl-7-chloro-6-hydroxy-tetrahydroisoquinolines were prepared to explore the influence of each series on the affinity for dopamine receptors. All the compounds displayed a high affinity for D(1)-like and/or D(2)-like dopamine receptors in striatal membranes, although they were unable to inhibit [(3)H]-dopamine uptake in striatal synaptosomes. The halogen placed on the benzylic ring in 1-benzyl-THIQs, compounds of the series 1, 2'-bromobenzyl derivatives with K(i) values into the nanomolar range, and the series 2, 2',4'-dichlorobenzyl-THIQ homologues, proves to be an important factor to modulate affinity at dopamine receptor.

  10. Benzyl Derivatives with in Vitro Binding Affinity for Human Opioid Receptors and Cannabinoid Receptors from the Fungus Eurotium repens

    Science.gov (United States)

    Bioassay-guided fractionation of the fungus Eurotium repens resulted in the isolation of two benzyl derivatives, repenol A (1) and repenol B (2). Seven known secondary metabolites were also isolated including five benzaldehyde compounds, flavoglaucin (3), tetrahydroauroglaucin (4), dihydroauroglauci...

  11. 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

  12. Synthesis and anticholinergic activity of 4-hydroxycoumarin derivatives containing substituted benzyl-1,2,3-triazole moiety.

    Science.gov (United States)

    Bagheri, Sahar Mohammad; Khoobi, Mehdi; Nadri, Hamid; Moradi, Alireza; Emami, Saeed; Jalili-Baleh, Leili; Jafarpour, Farnaz; Homayouni Moghadam, Farshad; Foroumadi, Alireza; Shafiee, Abbas

    2015-11-01

    A series of 4-hydroxycoumarin-derived compounds 8a-p containing N-benzyl-1,2,3-triazole motif were designed as AChE inhibitors. The title compounds were obtained conveniently using multicomponent click reaction. The in vitro anticholinesterase evaluation of synthesized compounds against AChE and BuChE showed that some of them are potent and selective inhibitors of AChE. Among them, 2-chlorobenzyl derivative 8k showed the most potent activity against AChE (IC50  = 0.18 μm). Its activity was also superior to that of standard drug tacrine. The kinetic study and molecular docking simulation of the most potent compound 8k were also described.

  13. Pseudo-Four Component Synthesis of Mono- and Di-Benzylated-1,2,3-Triazoles Derived from Aniline

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    Daniel Mendoza-Espinosa

    2013-12-01

    Full Text Available The pseudo-four component click synthesis of dibenzylated 1,2,3-triazoles derived from aniline is reported. The cycloaddition of sodium azide to N-(prop-2-ynyl-benzenamine (I in the presence of equimolar amounts of p-substituted benzyl derivatives, yields a mixture of mono- and dibenzylated 1,2,3-triazoles. When two equivalents of the benzyl derivative are added to the multicomponent reaction, the selective preparation of the dibenzylated compounds is achieved. The reactivity of the aniline N-H bond in monobenzylated 1,2,3-triazoles was tested by treatment with one equivalent of a p-substituted benzyl chloride at 40 °C, rendering the dibenzylated derivatives quantitatively.

  14. 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.

  15. Synthesis and antirhinovirus activity of new 3-benzyl chromene and chroman derivatives.

    Science.gov (United States)

    Conti, Cinzia; Desideri, Nicoletta

    2009-05-15

    A series of 3-benzyl chromenes and chromans were synthesized and tested in vitro against human rhinovirus (HRV) 1B and 14, two representative serotypes for rhinovirus group B and A, respectively. All the new compounds, with the exception of 3-benzyl-2H-chromene (3a), showed a potent activity against HRV serotype 1B within micro or submicromolar range (IC(50)s from 0.11 to 6.62 microM). The low cytotoxicity of all the derivatives resulted in compounds with high therapeutic index (TI). On the contrary, HRV 14 infection was only weakly inhibited by the majority of these compounds. The 3-benzylidenechromans 2b and 2c showed the highest anti-HRV 1B activity (IC(50) 0.12 and 0.11 microM, respectively) coupled with remarkable TI (625.00 and 340.91, respectively). Mechanism of action studies on (Z)-3-(4-chlorobenzylidene)chroman (2b) suggest that the new compounds behave as capsid binders and interfere with very early stages of HRV 1B replication, similarly to related flavanoids.

  16. Visible light mediated efficient oxidative benzylic sp(3) C-H to ketone derivatives obtained under mild conditions using O2.

    Science.gov (United States)

    Yi, Hong; Bian, Changliang; Hu, Xia; Niu, Linbin; Lei, Aiwen

    2015-09-25

    A photooxygenation of benzylic sp(3) C-H reaction has been demonstrated using O2 mediated by visible light. This protocol provides a simple and mild route to obtain ketones from benzylic sp(3) C-H bonds. Various benzylic sp(3) C-H bonds can be transformed into the desired ketone derivatives in moderate to good yields. The (18)O2 labelling experiments demonstrated that the oxygen introduced into ketone originated from dioxygen. A plausible mechanism has been proposed accordingly.

  17. Synthesis, antioxidant, enzyme inhibition and DNA binding studies of novel N-benzylated derivatives of sulfonamide

    Science.gov (United States)

    Abbas, Aadil; Murtaza, Shahzad; Tahir, Muhammad Nawaz; Shamim, Saima; Sirajuddin, Muhammad; Rana, Usman Ali; Naseem, Khadija; Rafique, Hummera

    2016-08-01

    A series of novel N-benzylated derivatives of sulfonamide were synthesized and characterized by FT-IR, NMR and XRD analysis. The synthesized compounds were assayed for their biological potential. The biological studies involved antioxidant, enzyme inhibition, and DNA interaction studies. Antioxidant potential was investigated by Ferric Reducing Antioxidant Power assay (FRAP) and DPPH free radical scavenging method, the capacity of synthesized compounds to inhibit the enzyme's activity was assayed by using the well-known Elman method whereas DNA interaction studies were carried out with the help UV-Vis absorption titration method. Moreover, a direct correlation between enzyme inhibition activity and concentration of the compounds was observed both in experimental and molecular docking studies. DNA interaction studies of the synthesized compounds showed weak interaction.

  18. Synthesis and antimicrobial activities of 1-(3-benzyl-4-oxo-3H-quinazolin-2-yl-4-(substitutedthiosemicarbazide derivatives

    Directory of Open Access Journals (Sweden)

    Alagarsamy Veerachamy

    2015-01-01

    Full Text Available A series of 1-(3-benzyl-4-oxo-3H-quinazolin-2-yl-4-(substituted thiosemicarbazides (AS1-AS10 were obtained by the reaction of 2-hydrazino- 3-benzyl quinazolin-4(3H-one (6 with different dithiocarbamic acid methyl ester derivatives. The key intermediate 3-benzyl-2-thioxo-2,3-dihydro-1Hquinazolin-4-one (4 was obtained by reacting benzyl amine (1 with carbon disulphide and sodium hydroxide in dimethyl sulphoxide to give sodium dithiocarbamate, which was methylated with dimethyl sulfate to yield the dithiocarbamic acid methyl ester (2 and condensed with methyl anthranilate (3 in ethanol yielded the desired compound (4 via the thiourea intermediate. The SH group of compound (4 was methylated for the favorable nucleophilic displacement reaction with hydrazine hydrate, which afford 2-hydrazino-3- benzyl-3H-quinazolin-4-one (6. The IR, 1H, and 13C NMR spectrum of these compounds showed the presence of peaks due to thiosemicarbazides, carbonyl (C=O, NH and aryl groups. The quinazolin-4-one moiety molecular ion peaks (m/z 144 were observed all the mass spectrum of compounds (AS1-AS10. Elemental (C, H, N analysis satisfactorily confirmed purity of the synthesized compounds and elemental composition. All synthesized compounds were also screened for their antimicrobial activity against selective gram positive and gram negative by agar dilution method. In the present study compounds AS8 and AS9 were emerged as the most active compounds of the series.

  19. Biocatalytic resolution of benzyl glycidyl ether and its derivates by Talaromyces flavus: effect of phenyl ring substituents on enantioselectivity.

    Science.gov (United States)

    Wei, Chun; Chen, Yunyun; Shen, Honglei; Wang, Shan; Chen, Lin; Zhu, Qing

    2012-08-01

    Talaromyces flavus containing a constitutive epoxide hydrolase (EH) resolved racemic benzyl glycidyl ether and nine derivatives into their (R)-enantiomers. After optimization of the fermentation conditions, the specific EH activity and biomass concentration were improved from 13.5 U/g DCW and 14.8 g DCW/l to 26.2 U/g DCW and 31.3 g DCW/l, respectively, with final values for e.e. ( s ) of 96 % and E of 13 with (R)-benzyl glycidyl ether. Substituents on the phenyl ring, however, gave low enantioselectivities.

  20. Synthesis of some novel fluoro isoxazolidine and isoxazoline derivatives using -benzyl fluoro nitrone via cycloaddition reaction in ionic liquid

    Indian Academy of Sciences (India)

    Bhaskar Chakraborty; Govinda Prasad Luitel

    2013-09-01

    1-Butyl-3-methylimidazolium-based ionic liquids are found to accelerate significantly the intermolecular 1,3-dipolar cycloaddition of -benzyl-fluoro nitrone derived in situ from 2,6-difluoro benzaldehyde and -benzylhydroxylamine, with activated alkenes and electron deficient alkynes to afford enhanced rates and improved yields of novel isoxazolidines and isoxazolines.

  1. Isomerism in benzyl-DOTA derived bifunctional chelators: implications for molecular imaging.

    Science.gov (United States)

    Payne, Katherine M; Woods, Mark

    2015-02-18

    The bifunctional chelator IB-DOTA has found use in a range of biomedical applications given its ability to chelate many metal ions, but in particular the lanthanide(III) ions. Gd(3+) in particular is of interest in the development of new molecular imaging agents for MRI and is highly suitable for chelation by IB-DOTA. Given the long-term instability of the aryl isothiocyanate functional group we have used the more stable nitro derivative (NB-DOTA) to conduct a follow-up study of some of our previous work on the coordination chemistry of chelates of these BFCs. Using a combination of NMR and HPLC to study the Eu(3+) and Yb(3+) chelates of NB-DOTA, we have demonstrated that this ligand will produce two discrete regioisomeric chelates at the point at which the metal ion is introduced into the BFC. These regioisomers are defined by the position of the benzylic substituent on the macrocyclic ring: adopting an equatorial position either at the corner or the side of the [3333] ring conformation. These regioisomers are incapable of interconversion and are distinct, separate structures with different SAP/TSAP ratios. The side isomer exhibits an increased population of the TSAP isomer, pointing to more rapid water exchange kinetics in this regioisomer. This has potential ramifications for the use of these two regioisomers of Gd(3+)-BFC chelates in MRI applications. We have also found that, remarkably, there is little or no freedom of rotation about the first single bond extending from the macrocyclic ring to the benzylic substituent. Since this is the linkage through which the chelate is conjugated to the remainder of the molecular imaging probe, this result implies that there may be reduced local rotation of the Gd(3+) chelate within a molecular imaging probe. This implies that this type of BFC could exhibit higher relaxivities than other types of BFC.

  2. Trapping of carbolithiation-derived tertiary benzylic α-lithio piperidines with carbon electrophiles: Controlling the formation of α-amino quaternary and vicinal stereocenters.

    Science.gov (United States)

    Beng, Timothy K; Fox, Nathan; Bassler, Daniel P; Alwali, Amir; Sincavage, Kayla; Silaire, Ann Wens V

    2015-08-28

    The interception of carbolithiation-derived tertiary benzylic α-lithio piperidines with carbon electrophiles, under HMPA-mediated conditions, has led to the diastereoselective synthesis of vicinally functionalized piperidines bearing α-amino quaternary stereocenters.

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

    Science.gov (United States)

    Matin, Mohammed Mahbubul; Nath, Amit R; Saad, Omar; Bhuiyan, Mohammad M H; Kadir, Farkaad A; Abd Hamid, Sharifah Bee; Alhadi, Abeer A; Ali, Md Eaqub; Yehye, Wageeh A

    2016-08-27

    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.

  4. A Case of Abnormal Bishler-Napieralski Cyclization Reaction, Leading to Form Benzyl Oxazole Derivatives

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A benzyl oxazole compound 3 was obtained with an excellent yield of 90% when N-acetyl-(2?methoxy-4?5?methylenedioxy)-phenylalanine methyl ester 1 was refluxed in POCl3 /benzene. However, the anticipated product 3,4-dihydroisoquinoline-3-carboxylic acid methyl ester 2 could not be found. The mechanism was discussed in this article.

  5. PPA-SiO2 Catalyzed Multi-component Synthesis of N-[α-(β-Hydroxy-α-naphthyl)(benzyl)]O-Alkyl Carbamate Derivatives

    Institute of Scientific and Technical Information of China (English)

    SHATERIAN,Hamid Reza; HOSSEINIAN,Asghar; GHASHANG,Majid

    2009-01-01

    Silica-supported polyphosphoric acid (PPA-SiO2) was found to be an efficient catalyst for the multi-component condensation reaction of benzaldehydes,2-naphthol,and methyl/benzyl carbamate to afford the corresponding N-[α-(β-hydroxy-α-naphthyl)(benzyl)]O-alkyl carbamate derivatives in good to excellent yields.This new approach consistently has the advantage of short reaction time,high conversions,clean reaction profiles,and simple experimental and work-up procedures.

  6. Influence of Fluorination on the Conformational Properties and Hydrogen-Bond Acidity of Benzyl Alcohol Derivatives

    Science.gov (United States)

    Bogdan, Elena; Compain, Guillaume; Mtashobya, Lewis; Le Questel, Jean-Yves; Besseau, François; Galland, Nicolas; Linclau, Bruno; Graton, Jérôme

    2015-01-01

    The effect of fluorination on the conformational and hydrogen-bond (HB)-donating properties of a series of benzyl alcohols has been investigated experimentally by IR spectroscopy and theoretically with quantum chemical methods (ab initio (MP2) and DFT (MPWB1K)). It was found that o-fluorination generally resulted in an increase in the HB acidity of the hydroxyl group, whereas a decrease was observed upon o,o′-difluorination. Computational analysis showed that the conformational landscapes of the title compounds are strongly influenced by the presence of o-fluorine atoms. Intramolecular interaction descriptors based on AIM, NCI and NBO analyses reveal that, in addition to an intramolecular OH⋅⋅⋅F interaction, secondary CH⋅⋅⋅F and/or CH⋅⋅⋅O interactions also occur, contributing to the stabilisation of the various conformations, and influencing the overall HB properties of the alcohol group. The benzyl alcohol HB-donating capacity trends are properly described by an electrostatic potential based descriptor calculated at the MPWB1K/6-31+G(d,p) level of theory, provided solvation effects are taken into account for these flexible HB donors. PMID:26130594

  7. 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.

  8. Benzylation of Aromatic Compounds with Benzyl Chloride Catalyzed by Nafion/SiO2 Nanocomposite Catalyst

    Institute of Scientific and Technical Information of China (English)

    Kun Guo YANG; Rui Mao HUA; Hai WANG; Bo Qing XU1

    2005-01-01

    In the presence of Nafion/SiO2 nanocomposite catalyst, the benzylation of aromatic compounds with benzyl chloride proceeded to afford diphenylmethane derivatives in high yields.The catalyst showed high catalytic activity not only for electron-rich aromatic compounds, but also for electron-poor aromatic compounds. Under identical conditions, the self-benzylation of benzyl chloride, and dibenzylation and/or multi-benzylation of aromatic compounds were negligible.

  9. 5,6-Dimethoxybenzofuran-3-one Derivatives: a Novel Series of Dual Acetylcholinesterase/Butyrylcholinesterase Inhibitors Bearing Benzyl Pyridinium Moiety

    Directory of Open Access Journals (Sweden)

    Mohammad Abdollahi

    2013-02-01

    Full Text Available Several studies have been focused on design and synthesis of multi-target anti Alzheimer compounds. Utilizing of the dual Acetylcholinesterase/Butyrylcholinesterase inhibitors has gained more interest to treat the Alzheimer’s disease. As a part of a research program to find a novel drug for treating Alzheimer disease, we have previously reported 6-alkoxybenzofuranone derivatives as potent acetylcholinesterase inhibitors. In continuation of our work, we would like to report the synthesis of 5,6-dimethoxy benzofuranone derivatives bearing a benzyl pyridinium moiety as dual Acetylcholinesterase/Butyrylcholinesterase inhibitors.MethodsThe synthesis of target compounds was carried out using a conventional method. Bayer-Villiger oxidation of 3,4-dimethoxybenzaldehyde furnished 3,4-dimethoxyphenol. The reaction of 3,4-dimethoxyphenol with chloroacetonitrile followed by treatment with HCl solution and then ring closure yielded the 5,6-dimethoxy benzofuranone. Condensation of the later compound with pyridine-4-carboxaldehyde and subsequent reaction with different benzyl halides afforded target compounds. The biological activity was measured using standard Ellman’s method. Docking studies were performed to get better insight into interaction of compounds with receptor.ResultsThe in vitro anti acetylcholinesterase/butyrylcholinesterase activity of compounds revealed that, all of the target compounds have good inhibitory activity against both Acetylcholinesterase/Butyrylcholinesterase enzymes in which compound 5b (IC50 = 52 ± 6.38nM was the most active compound against acetylcholinesterase. The same binding mode and interactions were observed for the reference drug donepezil and compound 5b in docking study.ConclusionsIn this study, we presented a new series of benzofuranone-based derivatives having pyridinium moiety as potent dual acting Acetylcholinesterase/Butyrylcholinesterase inhibitors.

  10. Predicting antiprotozoal activity of benzyl phenyl ether diamine derivatives through QSAR multi-target and molecular topology.

    Science.gov (United States)

    Garcia-Domenech, Ramon; Zanni, Riccardo; Galvez-Llompart, Maria; Galvez, Jorge

    2015-05-01

    Multi-target QSAR is a novel approach that can predict simultaneously the activity of a given chemical compound on different pharmacological targets. In this work, we have used molecular topology and statistical tools such as multilinear regression analysis and artificial neural networks, to achieve a multi-target QSAR model capable to predict the antiprotozoal activity of a group of benzyl phenyl ether diamine derivatives. The activity was related to three parasites with a high prevalence rate in humans: Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani. The multi-target model showed a high regression coefficient (R(2) = 0.9644 and R(2) = 0.9235 for training and test sets, respectively) and a low standard error of estimate (SEE = 0.279). Model validation was performed with an external test (R(2) = 0.9001) and a randomization analysis. Finally, the model was applied to the search of potential new active compounds.

  11. Structure of HIV-1 nonnucleoside reverse transcriptase inhibitors derivatives of N-benzyl-benzimidazole with different substituents in position 4

    Science.gov (United States)

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

    2010-01-01

    The constant development of new drugs against HIV-1 is necessary due to global expansion of AIDS and HIV-1 drug resistance. Nonnucleoside reverse transcriptase inhibitors of HIV-1 (NNRTIs) are potentially effective and nontoxic drugs in AIDS therapy. The crystal structures of six nonnucleoside inhibitors of HIV-1 reverse transcriptase (RT) derivatives of N-benzyl-benzimidazole are reported here. The investigated compounds belong to the group of so called "butterfly like" inhibitors with characteristic two π-electron moieties with an angled orientation. The structural data show the influence of the substituents of the benzimidazole ring on the geometry of the molecule and correlation between the structure of the inhibitor and its biological activity.

  12. 1-Benzyl-2-Phenylbenzimidazole (BPB, a Benzimidazole Derivative, Induces Cell Apoptosis in Human Chondrosarcoma through Intrinsic and Extrinsic Pathways

    Directory of Open Access Journals (Sweden)

    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.

  13. SOME BENZYL CARBOXYLATO DERIVATIVES AND ADDUCTS: SYNTHESIS, INFRARED AND NMR STUDIES

    Directory of Open Access Journals (Sweden)

    Daouda Ndoye

    2014-05-01

    Full Text Available Cy2NH2BzCO2•SnPh3Cl, Bz2NH2BzCO2•SnPh3Cl, BzCO2SnPh3•SnPh3Cl•1/4Bz2NH2Cl, Bz2NH2BzCO2•SnPhCl(OH2, Bz2NH2BzCO2•SnBu2Cl2, [BzCO2SnPh3][SnPhCl3•EtOH•H2O] adducts and complexes have been obtained on allowing Cy2NH2BzCO2 or Bz2NH2BzCO2•4H2O to react respectively with SnPh3Cl, SnPh2Cl2 or SnBu2Cl2 in specific ratios. The molecular structures of these compounds have been determined on the basis of infrared and NMR data. The suggested structures are discrete, dimers and tetramer, the tin atom being tetra-, penta- and hexacoordinated; the benzyl carboxylate anions are monodentate, bidentate and chelating and the cations involved in hydrogen bonds.

  14. 1, 3-Dipolar cycloaddition reactions: Synthesis of 5-benzyl-1-(2',4'-dibromophenyl)-3-(4"-substituted phenyl)-3a,4,6,6a-tetrahydro-1, 5-pyrrolo[3,4-]pyrazole-4,6-dione derivatives

    Indian Academy of Sciences (India)

    Manpreet Kaur; Baldev Singh; Baljit Singh

    2013-11-01

    1,3-Dipolar cycloaddition of nitrilimines 3 with -benzyl maleimide 4 has provided 5-benzyl-1-(2',4'-dibromophenyl)-3-(4"-substituted phenyl)-3a,4,6,6a-tetrahydro-1,5-pyrrolo[3,4-]pyrazole-4,6-dione derivatives 5 in excellent yield as the only isomer through a concerted pathway.

  15. 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.)

  16. Application of Magnetic Dicationic Ionic Liquid Phase Transfer Catalyst in Nuclophilic Substitution Reactions of Benzyl Halids in Water

    OpenAIRE

    Manouchehr Aghajeri; Ali Reza Kiasat; Bijan Mombeni Goodajdar

    2016-01-01

    magnetic dicationic ionic liquid (MDIL) was successfully prepared and evaluated as phase-transfer catalyst for nucleophilic substitution reactions. The reactions was occurred in water and furnished the corresponding benzyl derivatives in high yields. No evidence for the formation of by-product for example benzyl alcohol of the reaction was observed and the products were obtained in pure form without further purification.

  17. The FEMA GRAS assessment of hydroxy- and alkoxy-substituted benzyl derivatives used as flavor ingredients

    NARCIS (Netherlands)

    Adams, T.B.; Cohen, S.M.; Doull, J.; Feron, V.J.; Goodman, J.I.; Marnett, L.J.; Munro, I.C.; Portoghese, P.S.; Smith, R.L.; Waddell, W.J.; Wagner, B.M.

    2005-01-01

    This publication is the ninth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of int

  18. The FEMA GRAS assessment of hydroxy- and alkoxy-substituted benzyl derivatives used as flavor ingredients

    NARCIS (Netherlands)

    Adams, T.B.; Cohen, S.M.; Doull, J.; Feron, V.J.; Goodman, J.I.; Marnett, L.J.; Munro, I.C.; Portoghese, P.S.; Smith, R.L.; Waddell, W.J.; Wagner, B.M.

    2005-01-01

    This publication is the ninth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of

  19. The FEMA GRAS assessment of benzyl derivatives used as flavor ingredients

    NARCIS (Netherlands)

    Adams, T.B.; Cohen, S.M.; Doull, J.; Feron, V.J.; Goodman, J.I.; Marnett, L.J.; Munro, I.C.; Portoghese, P.S.; Smith, R.L.; Waddell, W.J.; Wagner, B.M.

    2005-01-01

    This publication is the eighth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of in

  20. N-substituted benzyl matrinic acid derivatives inhibit hepatitis C virus (HCV replication through down-regulating host heat-stress cognate 70 (Hsc70 expression.

    Directory of Open Access Journals (Sweden)

    Na-Na Du

    Full Text Available Heat-stress cognate 70 (Hsc70 is a host factor that helps hepatitis C virus (HCV to complete its life cycle in infected hepatocytes. Using Hsc70 as a target for HCV inhibition, a series of novel N-substituted benzyl matrinic/sophoridinic acid derivatives was synthesized and evaluated for their anti-HCV activity in vitro. Among these analogues, compound 7c possessing N-p-methylbenzyl afforded an appealing ability to inhibit HCV replication with SI value over 53. Furthermore, it showed a good oral pharmacokinetic profile with area-under-curve (AUC of 13.4 µM·h, and a considerably good safety in oral administration in mice (LD50>1000 mg/kg. As 7c suppresses HCV replication via an action mode distinctly different from that of the marketed anti-HCV drugs, it has been selected as a new mechanism anti-HCV candidate for further investigation, with an advantage of no or decreased chance to induce drug-resistant mutations.

  1. Benzyl-1,2,4-triazoles as CB1 Cannabinoid Receptor Ligands: Preparation and In Vitro Pharmacological Evaluation

    Science.gov (United States)

    Hernandez-Folgado, Laura; Decara, Juan; Rodríguez de Fonseca, Fernando; Goya, Pilar; Jagerovic, Nadine

    2016-01-01

    In a previous study, we have identified 3-alkyl-1,5-diaryl-1H-1,2,4-triazoles to be a novel class of cannabinoid type 1 receptor (CB1R) antagonists. In order to expand the number of cannabinoid ligands with a central 1,2,4-triazole scaffold, we have synthesized a novel series of 1-benzyl-1H-1,2,4-triazoles, and some of them were evaluated by CB1R radioligand binding assays. Compound 12a showed the most interesting pharmacological properties, possessing a CB1R affinity in the nanomolar range. PMID:27127651

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

    Science.gov (United States)

    Xu, Kehan; Huang, Lei; Xu, Zheng; Wang, Yanwei; Bai, Guojing; Wu, Qiuye; Wang, Xiaoyan; Yu, Shichong; Jiang, Yuanying

    2015-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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. ...

  5. Application of Magnetic Dicationic Ionic Liquid Phase Transfer Catalyst in Nuclophilic Substitution Reactions of Benzyl Halids in Water

    Directory of Open Access Journals (Sweden)

    Manouchehr Aghajeri

    2016-06-01

    Full Text Available magnetic dicationic ionic liquid (MDIL was successfully prepared and evaluated as phase-transfer catalyst for nucleophilic substitution reactions. The reactions was occurred in water and furnished the corresponding benzyl derivatives in high yields. No evidence for the formation of by-product for example benzyl alcohol of the reaction was observed and the products were obtained in pure form without further purification.

  6. Ecotoxicological evaluation of the biocidal agents sodium o-phenylphenol, sodium o-benzyl-p-chlorophenol, and sodium p-tertiary amylphenol.

    Science.gov (United States)

    Davoren, M; Fogarty, A M

    2005-02-01

    The ecotoxicological effects of three biocidal agents frequently employed as active ingredients in phenolic-based disinfectants were evaluated using a test battery comprising of organisms representing three aquatic trophic levels. Phenolic-based disinfectants are commonly used by mushroom growers to disinfect spent mushroom compost. In general, the most sensitive assay used in this study was the Microtox test. In the case of the fish lethality assay, sodium o-benzyl-p-chlorophenol was found to be slightly more sensitive than the bacterial test system. The freshwater alga and invertebrate tests were also among the most sensitive test species employed. The active ingredient, sodium o-benzyl-p-chlorophenol (with the exception of the Microtox assay), was the most toxic chemical tested on each species. The majority of ecotoxicity data obtained in this research has not been previously reported and may therefore assist in the management and planning decisions regarding the application of pesticides and utilisation of SMC.

  7. 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...

  8. Subcutaneous Construction of Engineered Adipose Tissue with Fat Lobule-Like Structure Using Injectable Poly-Benzyl-L-Glutamate Microspheres Loaded with Adipose-Derived Stem Cells.

    Directory of Open Access Journals (Sweden)

    Wentao Sun

    Full Text Available Porous microcarriers were fabricated from synthesized poly(γ-benzyl-L-glutamate (PBLG polymer to engineer adipose tissue with lobule-like structure via the injectable approach. The adipogenic differentiation of human adipose-derived stem cells (hASCs seeded on porous PBLG microcarriers was determined by adipogenic gene expression and glycerol-3-phosphate dehydrogenase enzyme activity. In vitro adipogenic cultivation was performed for 7 days, and induced hASC/PBLG complex (Adi-ASC/PBLG group was subcutaneously injected into nude mice. Injections of PBLG microcarriers alone (PBLG group and non-induced hASC/PBLG complex (ASC/PBLG group served as controls. Newly formed tissues were harvested after 4 and 8 weeks. Generation of subcutaneous adipose tissue with typical lobule-like structure separated by fibrous septa was observed upon injection of adipogenic-induced hASC/microsphere complex. Adipogenesis significantly increased in the Adi-ASC/PBLG group compared with the control groups. The angiogenesis in the engineered adipose tissue was comparable to that in normal tissue as determined by capillary density and luminal diameter. Cell tracking assay demonstrated that labeled hASCs remained detectable in the neo-generated tissues 8 weeks post-injection using green fluorescence protein-labeled hASCs. These results indicate that adipose tissue with typical lobule-like structure could be engineered using injectable porous PBLG microspheres loaded with adipogenic-induced hASCs.

  9. Subcutaneous Construction of Engineered Adipose Tissue with Fat Lobule-Like Structure Using Injectable Poly-Benzyl-L-Glutamate Microspheres Loaded with Adipose-Derived Stem Cells.

    Science.gov (United States)

    Sun, Wentao; Fang, Jianjun; Yong, Qi; Li, Sufang; Xie, Qingping; Yin, Jingbo; Cui, Lei

    2015-01-01

    Porous microcarriers were fabricated from synthesized poly(γ-benzyl-L-glutamate) (PBLG) polymer to engineer adipose tissue with lobule-like structure via the injectable approach. The adipogenic differentiation of human adipose-derived stem cells (hASCs) seeded on porous PBLG microcarriers was determined by adipogenic gene expression and glycerol-3-phosphate dehydrogenase enzyme activity. In vitro adipogenic cultivation was performed for 7 days, and induced hASC/PBLG complex (Adi-ASC/PBLG group) was subcutaneously injected into nude mice. Injections of PBLG microcarriers alone (PBLG group) and non-induced hASC/PBLG complex (ASC/PBLG group) served as controls. Newly formed tissues were harvested after 4 and 8 weeks. Generation of subcutaneous adipose tissue with typical lobule-like structure separated by fibrous septa was observed upon injection of adipogenic-induced hASC/microsphere complex. Adipogenesis significantly increased in the Adi-ASC/PBLG group compared with the control groups. The angiogenesis in the engineered adipose tissue was comparable to that in normal tissue as determined by capillary density and luminal diameter. Cell tracking assay demonstrated that labeled hASCs remained detectable in the neo-generated tissues 8 weeks post-injection using green fluorescence protein-labeled hASCs. These results indicate that adipose tissue with typical lobule-like structure could be engineered using injectable porous PBLG microspheres loaded with adipogenic-induced hASCs.

  10. Síntese e caracterização de complexos de platina(IV com derivados N-benzilados da 1,3-propanodiamina Synthesis and characterization of platinum(IV complexes derived from N-benzyl-propanediamine

    Directory of Open Access Journals (Sweden)

    Ana Paula Soares Fontes

    2010-01-01

    Full Text Available The present work describes the synthesis of a series of platinum(IV complexes with N-benzyl 1,3-propanediamine derivatives. Since substitution of the axial ligands in the platinum(IV complexes may alter their pharmacological properties, we have prepared complexes with different groups, such as hydroxide, chloride and acetate using a sequence of substitution reactions. The resulting complexes were fully characterized by IR, ¹H, 13C and 195Pt NMR spectroscopies, and elemental analysis.

  11. Design, synthesis, and structure-affinity relationships of regioisomeric N-benzyl alkyl ether piperazine derivatives as sigma-1 receptor ligands.

    Science.gov (United States)

    Moussa, Iman A; Banister, Samuel D; Beinat, Corinne; Giboureau, Nicolas; Reynolds, Aaron J; Kassiou, Michael

    2010-08-26

    A series of N-(benzofuran-2-ylmethyl)-N'-benzylpiperazines bearing alkyl or fluoroalkyl aryl ethers were synthesized and evaluated at various central nervous system receptors. Examination of in vitro sigma1 {[3H]+-pentazocine} and sigma2 ([3H]DTG) receptor binding profiles of piperazines 11-13 and 25-36 revealed several highly potent and sigma1 selective ligands, notably, N-(benzofuran-2-ylmethyl)-N'-(4'-methoxybenzyl)piperazine (13, Ki=2.7 nM, sigma2/sigma1=38) and N-(benzofuran-2-ylmethyl)-N'-(4'-(2''-fluoroethoxy)benzyl)piperazine (30, Ki=2.6 nM, sigma2/sigma1=187). Structural features for optimal sigma1 receptor affinity and selectivity over the sigma2 receptor were identified. On the basis of its favorable log D value, 13 was selected as a candidate for the development of a sigma1 receptor positron emission tomography radiotracer. [11C]13 showed high uptake in the brain and other sigma receptor-rich organs of a Papio hamadryas baboon. The in vivo evaluation of [11C]13 indicates that this radiotracer is a suitable candidate for imaging the sigma1 receptor in neurodegenerative processes.

  12. Crystal structures of the even and odd bolaform amino acid derivatives (11-N-[benzyloxycarbonyl-L-alanyl]aminoundecanoyl)-L-alanyl benzyl ester and (12-N-[benzyloxycarbonyl-L-alanyl]aminododecanoyl)-L-alanyl benzyl ester.

    Science.gov (United States)

    Schade, B; Hubert, V; André, C; Luger, P; Fuhrhop, J H

    1997-04-01

    Reaction of two alpha, omega-aminocarboxylic acids with N- and C-protected alanine leads to bolaform compounds with two secondary amide groups on one end and one such group at the other end. Unsymmetric sheet-like structures are formed in the crystals. (11-N-[Benzyloxycarbonyl-L-alanyl] aminoundecanoyl)-L-alanyl benzyl ester (1) and (12-N-[benzyloxycarbonyl-L-alanyl] aminododecanoyl)-L-alanyl benzyl ester (2) form triclinic crystals (spacegroup P1, No.1) with a = 4.917, b = 5.614, c = 29.02 A. alpha = 88.40, beta = 93.50, gamma = 100.21 degrees, Z = 1 (1) and a = 4.954, b = 5.613, c = 30.23 A, alpha = 93.44, beta = 90.07, gamma = 104.15 degrees, Z = 1 (2). The crystal structures were solved via direct methods and refined to R = 0.040 (1) and 0.078 (2) from 2441 and 2725 reflections.

  13. Single Pot Benzylation of O-Xylene with Benzyl Chloride and Benzyl Alcohol Over Pillared Montmorillonites

    Directory of Open Access Journals (Sweden)

    Kurian Manju

    2014-09-01

    Full Text Available Improvement of product selectivity is a major concern of the day. Presence of a coreactant can alter the rate as well as product selectivity of many key reactions like Friedel-Crafts benzylation. Single pot benzylation of o-xylene with benzyl chloride and benzyl alcohol was studied over transition metal exchanged pillared clay catalysts. Complete conversion of benzyl alcohol occured within one hour with 100% monoalkylated product selectivity. The reaction of o-xylene with benzyl alcohol was found to proceed fast in presence of benzyl chloride in single pot, than when present alone as the benzylating species. This enhancement occurs at the expense of no reaction of benzyl chloride, which when present alone reacts faster than benzyl alcohol. Existence of a second transition metal exchanged between the pillars increased the rate of the reaction. A detailed investigation of the reaction variables suggested preferential adsorption of benzyl alcohol to catalyst active sites as the reason.

  14. Access to the substituted benzyl-1,2,3-triazolyl hesperetin derivatives expressing antioxidant and anticancer effects

    Directory of Open Access Journals (Sweden)

    Bhupendra Mistry

    2017-02-01

    Full Text Available Azide–alkyne cycloaddition was attempted to generate a flavanone hesperetin based phenyl substituted 1,2,3-triazolyls as semi-synthetic natural product derivatives utilizing copper-catalyzed click chemistry. All final compounds were analyzed for their in vitro antioxidant abilities using DPPH and ABTS bioassay. Moreover, cancerous cell inhibitory prospect of titled compounds was screened against cervical cancer cell lines, HeLa and CaSki and an ovarian cancer cell line SK-OV-3 implementing SRB assay. Bearable toxicity of 6a-s was examined employing Madin–Darby canine kidney (MDCK non-cancer cell line. Overall, 6a-s indicated remarkable antioxidant power in scavenging DPPH·− and ABTS·−+; particularly, an analog 6o with meta-methoxy substituent showed most potent radical scavenging activity, whereas scaffolds 6d with para-fluoro, 6k with ortho-methyl, and 6o with meta-methoxy performed excellently in inhibiting both the cervical cancer cell lines and analog 6q with meta-trifluoromethyl substituent expressed excellent sensitivity toward ovarian cancer cell line. From the structure–activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the phenyl ring attached to the triazole core may contribute to the anticipated antioxidant and anticancer action. Structure of final compounds was adequately confirmed exploring different spectroscopic techniques and elemental analysis in addition to the measurements of some physical properties.

  15. Synthesis and Evaluation of Optical 2-Benzyl-5-bromo-4- oxopentanoic Acids as Transition-state Analog Inhibitors against Carboxypeptidase A

    Institute of Scientific and Technical Information of China (English)

    JIN,Jing-Yi; WANG,Shou-Feng; XUAN,Wei; SHENG,Ji-Wen; WANG,Si-Hong; TIAN,Guan-Rong

    2008-01-01

    Both enantiomers of 2-benzyl-5-bromo-4-oxopentanoic acid were prepared utilizing the diazo ketones as the key intermediates. The compounds were assayed for inhibitory activity against carboxypeptidase A (CPA, EC 3.4.17.1). The (R)-form is 260-fold more potent than the corresponding (S)-form. The finding that (R)-form, which belongs to the L-series, is mostly responsible for the inhibitory activity accords with the substrate specificity of CPA.For comparison, both the optical forms of 2-benzyl-4-oxopentanoic acid were also synthesized and evaluated as the inhibitors against CPA. These results reveal that the introduction of a bromo group at the α-position of ketones can significantly enhance the electrophilicity of the carbonyl group. Further molecular docking study suggested that the gem-diol form of the α-bromo ketone, which mimics the transition state in the CPA catalytic process, could chelate the zinc ion in the active site of CPA and thus result in the strong inhibition.

  16. Novel Nonsymmetrically p-Benzyl-Substituted (Benzimidazole N-Heterocyclic Carbene-Silver(I Acetate Complexes: Synthesis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Frauke Hackenberg

    2012-01-01

    Full Text Available Nonsymmetrically substituted N-heterocyclic carbene (NHC precursors 1a–d and 3a–d were synthesised by first reacting 1H-(benzimidazole with p-cyanobenzyl bromide to give 4-(1H-imidazole-1-ylmethylbenzonitrile (1 and 4-(1H-benzimidazole-1-ylmethylbenzonitrile (3 and afterwards introducing benzyl bromide, 1-(bromomethyl-4-methylbenzene, 1-(bromomethyl-4-methoxybenzene, and methyl 4-(bromomethylbenzoate. The NHC-silver(I acetate complexes (1-benzyl-3-(4-cyanobenzyl-2,3-dihydro-1H-imidazole-2-ylidene silver(I acetate (2a, (1-(4-cyanobenzyl-3-(4-methylbenzyl-2,3-dihydro-1H-imidazole-2-ylidene silver(I acetate (2b, (1-(4-cyanobenzyl-3-[4-(methoxycarbonylbenzyl]-2,3-dihydro-1H-imidazole-2-ylidene silver(I acetate (2c, (1-benzyl-3-(4-cyanobenzyl-2,3-dihydro-1H-benzimidazole-2-ylidene silver(I acetate (4a, (1-(4-cyanobenzyl-3-(4-methylbenzyl-2,3-dihydro-1H-benzimidazole-2-ylidene silver(I acetate (4b, (1-(4-cyanobenzyl-3-(4-methoxybenzyl-2,3-dihydro-1H-benzimidazole-2-ylidene silver(I acetate (4c, and (1-(4-cyanobenzyl-3-[4-(methoxycarbonylbenzyl]-2,3-dihydro-1H-benzimidazole-2-ylidene silver(I acetate (4d were yielded by reacting these NHC precursors with silver(I acetate. The silver(I acetate complex 4b was characterised by single crystal X-ray diffraction. Preliminary in vitro antibacterial studies against the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli, using the Kirby-Bauer disc diffusion method, were carried out on the seven NHC-silver(I acetate complexes 2a–c and 4a–d. Also the IC50 values of these seven complexes were determined by an MTT-based assay against the human renal cancer cell line Caki-1. The complexes 2a–c and 4a–c revealed the following IC50 values, respectively, 25 (±1, 15 (±2, 5.4 (±0.8, 16 (±2, 7.1 (±1, 20 (±4, and 14 (±1 μM.

  17. Synthesis and Bioactivity of Some New 2-(Alkoxy carbonyl alkyl)-6-bromo-3,4-dihydro-3-(α-methyl benzyl)-2-oxobenzo[e][2H-1,3,2-oxazaphosphinine]Derivatives

    Institute of Scientific and Technical Information of China (English)

    SRINIVASULU,K; SURESH KUMAR,K; HARI BABU,B; STEPHEN BABU,M.F; NAGA RAJU,C; SURESH REDDY,C

    2009-01-01

    Synthesis of some new 2-(alkoxy carbonyl alkyl)-6-bromo-3,4-dihydro-3-(α-methyl benzyl)-2-oxo-3-benzo[e][2H-1,3,2-oxazaphosphinine]derivatives was accomplished through a two step process,which involves the condensation of 2-[(α-methylbenzyl amino)methyl]-4-bromophenol (1) with phosphorus oxychloride in equimolar quantities in the presence of triethylamine in dry toluene in 50-55 ℃ producing the corresponding intermediate (2),and subsequent reaction with the amino acid alkyl ester in dry tetrahydrofuran in the presence of triethylamine at different temperatures.They exhibited significant antibacterial and fungal activity.

  18. Novel N-(3-carboxyl-9-benzyl-beta-carboline-1-yl)ethylamino acids: synthesis, anti-tumor evaluation, intercalating determination, 3D QSAR analysis and docking investigation.

    Science.gov (United States)

    Wu, Jianhui; Zhao, Ming; Qian, Keduo; Lee, Kuo-Hsiung; Morris-Natschke, Susan; Peng, Shiqi

    2009-10-01

    Sixteen novel N-(3-carboxyl-9-benzyl-beta-carboline-1-yl)ethylamino acids (6a-p) were synthesized as intercalating lead compounds. In the in vitro cytotoxic assay their IC(50) values against five human carcinoma cell lines ranged from 10.95 microM to about 400 microM. On S180 mouse model eight of them exhibited anti-tumor action, four of them showed the same anti-tumor potency as that of cytarabine. The preliminary toxicity evaluation revealed that the LD(50) values of 6a-p should be more than 500 mg/kg. With CT DNA as model system an intercalating mechanism was explored. Using 3D QSAR analysis the relationship of the in vivo anti-tumor activity and the structure was quantitatively described. By docking 6a-p onto d(CGATCG)(2) oligonucleotides the intercalation was demonstrated.

  19. Synthesis and in vivo evaluation of 11-substituted estradiol derivatives as anti-implantation agents.

    Science.gov (United States)

    Dwivedy, Indra; Gupta, Atul; Grover, Arvinder; Srivastava, Vandana; Singh, Man Mohan; Ray, Suprabhat

    2008-07-15

    Synthesis of 11-substituted estradiol derivatives (12-17) has been carried out by the Grignard reaction with alkyl, allyl, and benzyl halides on 17beta-hydroxy-3-methoxy-11-oxo-estra-1,3,5(10),8(9)-tetraene (10). The novel compounds (10 and 12-17) were evaluated for their preliminary post-coital contraceptive (anti-implantation) activity in Sprague-Dawley rats. The tested compounds were administered orally and showed significant anti-implantation activity. Compound 13 is the most potent compound in the series which showed 100% contraceptive efficacy at 1.25 mg kg(-1).

  20. Levels of prostaglandins and arachidonic acid in UV-B irradiated human skin before and after topical application of benzyl-2,5-diacetoxybenzoate, a salicylic acid derivative

    Energy Technology Data Exchange (ETDEWEB)

    Barr, R.M.; Black, A.K.; Mallet, A.I.; Greaves, M.W.

    1982-07-01

    Benzyl-2,5-diacetoxybenzoate (BDAB) was tested for anti-inflammatory activity on experimentally inflamed skin. Human abdominal skin was irradiated with three minimal erythema doses of UV-B (290-320nm) radiation to give a maximum erythema at 24 hours with an associated rise in PGE2 and PGF2 alpha levels measured by gas chromatography-mass spectrometry. Topical application of a 1% w/w preparation of BDAB neither decreased the evoked erythema nor diminished the rise in PGE2 and PGF2 alpha concentrations. BDAB, applied topically, was judged to be ineffectual as an anti-inflammatory agent in UV-B erythema.

  1. Palladium-catalyzed α-arylation of benzylic phosphine oxides.

    Science.gov (United States)

    Montel, Sonia; Jia, Tiezheng; Walsh, Patrick J

    2014-01-03

    A novel approach to prepare diarylmethyl phosphine oxides from benzyl phosphine oxides via deprotonative cross-coupling processes (DCCP) is reported. The optimization of the reaction was guided by High-Throughput Experimentation (HTE) techniques. The Pd(OAc)2/Xantphos-based catalyst enabled the reaction between benzyl diphenyl or dicyclohexyl phosphine oxide derivatives and aryl bromides in good to excellent yields (51-91%).

  2. Origin of the SN2 benzylic effect.

    Science.gov (United States)

    Galabov, Boris; Nikolova, Valia; Wilke, Jeremiah J; Schaefer, Henry F; Allen, Wesley D

    2008-07-30

    The S N2 identity exchange reactions of the fluoride ion with benzyl fluoride and 10 para-substituted derivatives (RC6H 4CH 2F, R = CH3, OH, OCH 3, NH2, F, Cl, CCH, CN, COF, and NO2) have been investigated by both rigorous ab initio methods and carefully calibrated density functional theory. Groundbreaking focal-point computations were executed for the C6H5CH 2F + F (-) and C 6H 5CH2Cl + Cl (-) SN2 reactions at the highest possible levels of electronic structure theory, employing complete basis set (CBS) extrapolations of aug-cc-pV XZ (X = 2-5) Hartree-Fock and MP2 energies, and including higher-order electron correlation via CCSD/aug-cc-pVQZ and CCSD(T)/aug-cc-pVTZ coupled cluster wave functions. Strong linear dependences are found between the computed electrostatic potential at the reaction-center carbon atom and the effective SN2 activation energies within the series of para-substituted benzyl fluorides. An activation strain energy decomposition indicates that the SN2 reactivity of these benzylic compounds is governed by the intrinsic electrostatic interaction between the reacting fragments. The delocalization of nucleophilic charge into the aromatic ring in the SN2 transition states is quite limited and should not be considered the origin of benzylic acceleration of SN2 reactions. Our rigorous focal-point computations validate the benzylic effect by establishing SN2 barriers for (F (-), Cl (-)) identity exchange in (C6H5CH2F, C6H 5CH2Cl) that are lower than those of (CH3F, CH3Cl) by (3.8, 1.6) kcal mol (-1), in order.

  3. 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.

  4. Financial Derivatives (Based on Two Supports Evaluation

    Directory of Open Access Journals (Sweden)

    Tiberiu Socaciu

    2011-10-01

    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 am
    option based on gold, when national currency has a great float.
    Keywords: Financial derivatives, derivatives evaluation, derivatives based on two supports, extended Itō like lemma.

  5. Oxidation of Fluoroalkanesulfonyl fluoride/hydrogen peroxide/base/acetone System with Benzyl Alcohol Derivatives%氟烷磺酰氟/双氧水/碱/丙酮体系与苄醇衍生物的氧化反应

    Institute of Scientific and Technical Information of China (English)

    严兆华; 胡伟; 田伟生; 许云

    2013-01-01

    Oxidation of fluoroalkanesulfonyl fluoride/hydrogen peroxide/base/acetone system with six benzyl alcohol derivative substrates was reported. Fluoroalkanesulfonyl fluorides(RfSO2F) include 5-H-3-oxa-l ,1,2, 2,4,4,5, 5-octafluoropentanesulfonyl fluoride ( HCF2CF2OCF2CF2SO2F ) , perfluorobutanesulfonyl fluoride (n-C4F9SO2F) and perfluorooctanesulfonyl fluoride( n-C8F17SO2F). The optimized reaction condition was n ( Substrate) : n ( Rf SO2 F):n(H2O2):?( NaOH) = 1 : 4 : 8 : 8, solvent was acetone, reaction temperature was 20 °C and reaction time was 24 h. Yield of product ketones was 23%—92%. A plausible mechanism was proposed. Experimental results showed that in-situ generated fluorinatedalkano persulfonic acid intermediate could efficiently oxidize acetone and resulted dimethyl dioxirane could oxidize benzyl alcohol derivatives yielding corresponding ketones. The oxidizing ability of fluoroalkanesulfonyl fluoride/hydrogen peroxide/base/acetone system for the oxidation of benzyl alcohol derivatives is similar to that of the traditional Oxone/CH3COCH3 system. A novel method for the in-situ generation of dimethyl dioxirane was developed.%研究了氟烷磺酰氟/双氧水/氢氧化钠/丙酮体系与6个苄醇衍生物的氧化反应,其中氟烷磺酰氟包括HCF2CF2OCF2 CF2SO2F,n-C4F9 SO2F和n-C8F17SO2F.最优反应条件为n(苄醇衍生物)∶n(氟烷磺酰氟)∶n(双氧水)∶n(氢氧化钠)=1∶4∶8∶8,溶剂为丙酮,反应温度为20℃,反应时间为24 h.产物酮的收率为23% ~92%.探讨了该氧化反应的机理,原位生成的氟烷基过氧磺酸中间体可将丙酮氧化为二甲基二氧杂环丙烷,进而将反应体系中共存的苄醇衍生物氧化成相应的产物酮.氟烷磺酰氟/双氧水/氢氧化钠/丙酮体系原位生成的二甲基二氧杂环丙烷氧化苄位羟基的能力和传统的Oxone/CH3COCH3体系相当.本研究提供了一种新颖的原位制备二甲基二氧杂环丙烷的方法.

  6. Lewis Acid Catalyzed Benzylic Bromination

    OpenAIRE

    Shibatomi, Kazutaka; Zhang, Yanhua; Yamamoto, Hisashi

    2008-01-01

    Lewis acid catalyzed bromination on aromatic side chain was achieved efficiently by using 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as a bromination reagent under mild conditions. Zirconium(IV) chloride showed the highest catalytic activity for the benzylic bromination. It was revealed that the present Lewis acid catalysis proceeds via the radical generation pathway. In contrast to Lewis acid catalysis, Brønsted acid promoted aromatic ring bromination without any benzylic bromination. Monobro...

  7. Synthesis & Bio-Evaluation of 4-Amino-5-Benzyl-2, 4-Dihydro- 3H-1, 2, 4-Triazole-3-Thione Capped Silver Nano Particles

    Directory of Open Access Journals (Sweden)

    M. Padma

    2015-02-01

    Full Text Available Synthesis of 4-amino-5-benzyl-2,4-dihydro-3H-1,2,4-triazole-3-thione Capped Silver NanoParticles by a simple procedure. Spherical shaped Capped Ag-NPs with average size of 14.65 nm are obtained by the treatment of aqueous silver ions with hot ethanolic solution of 4-amino-5-benzyl-2,4-dihydro-3H-1,2,4-triazole-3-thione as Stabilizing/Reducing agent. The Nanoparticles are characterized using TEM, XRD and FTIR studies. The synthesized Nanoparticles were tested for in vitro antimicrobial activity at concentrations of 50, 100, 200 μg /ml. The Nanoparticles showed good activity, nearly equal to the inhibition zone value of ciprofloxacin, against the E.coli bacteria. For the antifungal activity, the compound showed equipotent activity against A.niger.

  8. Fragrance material review on benzyl butyrate.

    Science.gov (United States)

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of benzyl butyrate when used as a fragrance ingredient is presented. Benzyl butyrate is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for benzyl butyrate were evaluated, then summarized, and includes: physical properties, acute toxicity, skin irritation, skin sensitization, toxicokinetics, and repeated dose data. A safety assessment of the entire AAASAE 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 AAASAE in fragrances. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Fragrance material review on benzyl isobutyrate.

    Science.gov (United States)

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of benzyl isobutyrate when used as a fragrance ingredient is presented. Benzyl isobutyrate is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for benzyl isobutyrate were evaluated, then summarized, and includes: physical properties, acute toxicity, skin irritation, or skin sensitization data. A safety assessment of the entire AAASAE 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 AAASAE in fragrances. Copyright © 2012 Elsevier Ltd. 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. Primary anti-proliferative activity evaluation of 1-(quinolizidin-1'-yl)methyl- and 1-([Formula: see text]-tert-amino)alkyl-substituted 2-phenyl-, 2-benzyl- and 2-[(benzotriazol-1/2-yl)methyl]benzimidazoles on human cancer cell lines.

    Science.gov (United States)

    Tonelli, Michele; Tasso, Bruno; Mina, Lorenzo; Paglietti, Giuseppe; Boido, Vito; Sparatore, Fabio

    2013-08-01

    Twenty benzimidazole derivatives bearing in position 1 a ([Formula: see text]-tert-amino)alkyl chain (mainly quinolizidin-1-ylmethyl) and in position 2 an aromatic moiety (phenyl, benzyl or benzotriazol-1/2-ylmethyl) were evaluated at the National Cancer Institute (NCI) for anti-proliferative activity against a panel of 60 human cancer cell lines. Four compounds (6, 7, 9 and 10) displayed a large spectrum of activity with [Formula: see text] 10 [Formula: see text] on 24-57 cell lines, while thirteen compounds exhibited sub-micromolar or even nanomolar activity against single cell lines, such as leukemia CCRF-CEM, HL-60 and MOLT-4, CNS cancer SF-268 and, particularly, renal cancer UO-31, sometimes with outstanding selectivity (compounds 5-7, 11, 13 and 18).

  12. 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.

  13. Synthesis and pharmacological evaluation of 1-alkyl-N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]piperidine-4-carboxamide derivatives as novel antihypertensive agents.

    Science.gov (United States)

    Watanuki, Susumu; Matsuura, Keisuke; Tomura, Yuichi; Okada, Minoru; Okazaki, Toshio; Ohta, Mitsuaki; Tsukamoto, Shin-ichi

    2011-01-01

    We synthesized and evaluated inhibitory activity against T-type Ca(2+) channels for a series of 1-alkyl-N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]piperidine-4-carboxamide derivatives. Structure-activity relationship studies have revealed that the isopropyl substituent at the benzylic position plays an important role in exerting potent inhibitory activity, and the absolute configuration of the benzylic position was found to be opposite that of mibefradil, which was first launched as a new class of T-type Ca(2+) channel blocker. Oral administration of N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]-1-[2-(3-methoxyphenyl)ethyl]piperidine-4-carboxamide (17f) lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, an adverse effect often caused by traditional L-type Ca(2+) channel blockers.

  14. Synthesis and antibacterial evaluation of novel 8-fluoro Norfloxacin derivatives as potential probes for methicillin and vancomycin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Sunduru, Naresh; Gupta, Leena; Chauhan, Kuldeep; Mishra, Nripendra N; Shukla, Praveen K; Chauhan, Prem M S

    2011-04-01

    A series of novel 8-fluoro Norfloxacin derivatives and the hybrids of its piperazinyl derivatives incorporated with 1,3,5-triazine and pyrimidine were synthesized. All the above compounds were evaluated for their antibacterial activity against Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus and methicillin & vancomycin-resistant S. aureus. Among all, compounds having Morpholine, N-methyl/phenyl/benzyl/pyrimidinyl piperazines and n-butylamine substitution at C-7 position, have shown increased potency in comparison to norfloxacin and ciprofloxacin. Copyright © 2011. Published by Elsevier Masson SAS.

  15. 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.

  16. Synthesis and biological evaluation of indazole derivatives.

    Science.gov (United States)

    Claramunt, Rosa M; López, Concepción; López, Ana; Pérez-Medina, Carlos; Pérez-Torralba, Marta; Alkorta, Ibon; Elguero, José; Escames, Germaine; Acuña-Castroviejo, Darío

    2011-04-01

    The inhibition of neuronal and inducible nitric oxide synthases (nNOS and iNOS) by a series of 36 indazoles has been evaluated, showing that most of the assayed derivatives are better iNOS than nNOS inhibitors. A parabolic model relating the iNOS inhibition percentage with the difference, E(rel), between stacking and apical interaction energies of indazoles with the active site of the NOS enzyme has been established.

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

    Science.gov (United States)

    Saxena, Sandeep K.; Viswanadham, Nagabhatla

    2017-01-01

    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 N2 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.

  18. Synthesis and biological evaluation of novel imidazolidine derivatives as candidates to schistosomicidal agents

    Science.gov (United States)

    Matos-Rocha, Thiago José; de Lima, Maria do Carmo Alves; da Silva, Anekécia Lauro; de Oliveira, Jamerson Ferreira; Gouveia, Allana Lemos Andrade; da Silva, Vinícius Barros Ribeiro; de Almeida, Antônio Sérgio Alves; Brayner, Fábio André; Cardoso, Pablo Ramon Gualberto; Pitta-Galdino, Marina da Rocha; Pitta, Ivan da Rocha; Rêgo, Moacyr Jesus Barreto de Melo; Alves, Luiz Carlos; Pitta, Maira Galdino da Rocha

    2017-01-01

    ABSTRACT Introduction: Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives. Material and methods: We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed. Results: LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms. Conclusion: The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity. PMID:28380119

  19. Convenient One-Pot Synthesis of 2,4,5-Triaryl-1H-imidazoles from Arylaldehydes, Benzyl Alcohols, or Benzyl Halides with HMDS in the Presence of Molecular Iodine

    Energy Technology Data Exchange (ETDEWEB)

    Veisi, Hojat; Heshmati, Leila [Payame Noor University, Tehran (Iran, Islamic Republic of); Khazaei, Ardashir [Bu-Ali Sina University, Hamedan (Iran, Islamic Republic of); Hemmati, Saba [Islamic Azad University, Kermanshah (Iran, Islamic Republic of)

    2012-04-15

    A one-pot efficient procedure for the synthesis of 2,4,5-triaryl-1H-imidazole derivatives in good to excellent yields by reaction between hexamethyldisilazane and arylaldehydes, benzyl alcohols, benzyl halides in the presence of molecular iodine has been developed. The remarkable advantages of this method are the simple workup procedure, high yields of products, and the availability of reagents

  20. Solvent-free alkylation of dimethyl malonate using benzyl alcohols catalyzed by FeCl3/SiO2

    Institute of Scientific and Technical Information of China (English)

    Mohammad Reza Shushizadeh; Masumeh Kiany

    2009-01-01

    Activated methylene compound such as dimethyl malonate reacted readily with benzylic alcohols in the presence of ferric chloride/silica gel mixture(FeCl3/SiO2)under microwave irradiation to produce benzylic derivative of dimethyl malonate in high yields in solvent-free condition.

  1. Synthesis and pharmacological evaluation of 1-alkyl-N-[2-ethyl-2-(4-fluorophenyl)butyl]piperidine-4-carboxamide derivatives as novel antihypertensive agents.

    Science.gov (United States)

    Watanuki, Susumu; Matsuura, Keisuke; Tomura, Yuichi; Okada, Minoru; Okazaki, Toshio; Ohta, Mitsuaki; Tsukamoto, Shin-Ichi

    2011-09-15

    We synthesized and evaluated inhibitory activity against T-type Ca(2+) channels for a series of 1-alkyl-N-[2-ethyl-2-(4-fluorophenyl)butyl]piperidine-4-carboxamide derivatives. Structure-activity relationship studies have revealed that dialkyl substituents at the benzylic position play an important role in increasing inhibitory activity. Oral administration of N-[2-ethyl-2-(4-fluorophenyl)butyl]-1-(2-phenylethyl)piperidine-4-carboxamide (20d) lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, which is often caused by traditional L-type Ca(2+) channel blockers.

  2. Antimicrobial, antioxidant, cytotoxic and molecular docking properties of N-benzyl-2,2,2-trifluoroacetamide

    Science.gov (United States)

    Balachandran, C.; Kumar, P. Saravana; Arun, Y.; Duraipandiyan, V.; Sundaram, R. Lakshmi; Vijayakumar, A.; Balakrishna, K.; Ignacimuthu, S.; Al-Dhabi, N. A.; Perumal, P. T.

    2015-02-01

    N-Benzyl-2,2,2-trifluoroacetamide was obtained by acylation of benzylamine with trifluoroacetic anhydride using Friedel-Crafts acylation method. The synthesised compound was confirmed by spectroscopic and crystallographic techniques. N-Benzyl-2,2,2 -trifluoroacetamide was assessed for its antimicrobial, antioxidant, cytotoxic and molecular docking properties. It showed good antifungal activity against tested fungi and moderate antibacterial activity. The minimum inhibitory concentration values of N-benzyl-2,2,2 -trifluoroacetamide against fungi were 15.62 μg/mL against A. flavus, 31.25 μg/mL against B. Cinerea and 62.5 μg/mL against T. mentagrophytes, Scopulariopsis sp., C. albicans and M. pachydermatis. N-Benzyl-2,2,2-trifluoroacetamide showed 78.97 ± 2.24 of antioxidant activity at 1,000 μg/mL. Cupric ion reducing antioxidant capacity of N-benzyl-2,2,2-trifluoroacetamide was dependent on the concentration. Ferric reducing antioxidant power assay of N-benzyl-2,2,2-trifluoroacetamide showed (1.352 ± 0.04 mM Fe(II)/g) twofold higher value compared to the standard. N-Benzyl-2,2,2-trifluoroacetamide showed 75.3 % cytotoxic activity at the dose of 200 μg/mL with IC50 (54.7 %) value of 100 μg/mL. N-Benzyl-2,2,2-trifluoroacetamide was subjected to molecular docking studies for the inhibition AmpC beta-lactamase, Glucosamine-6-Phosphate Synthase and lanosterol 14 alpha-demethylase (CYP51) enzymes which are targets for antibacterial and antifungal drugs. Docking studies of N-benzyl-2,2,2-trifluoroacetamide showed low docking energy. N-Benzyl-2,2,2-trifluoroacetamide can be evaluated further for drug development.

  3. Hyaluronan Benzyl Ester as a Scaffold for Tissue Engineering

    OpenAIRE

    2009-01-01

    Tissue engineering is a multidisciplinary field focused on in vitro reconstruction of mammalian tissues. In order to allow a similar three-dimensional organization of in vitro cultured cells, biocompatible scaffolds are needed. This need has provided immense momentum for research on “smart scaffolds” for use in cell culture. One of the most promising materials for tissue engineering and regenerative medicine is a hyaluronan derivative: a benzyl ester of hyaluronan (HYAFF®). HYAFF® can be proc...

  4. Synthesis and Antimicrobial Evaluation of Some Novel Trisubstituted s-Triazine Derivatives Based on Isatinimino, Sulphonamido, and Azacarbazole

    Directory of Open Access Journals (Sweden)

    Sonika Jain

    2013-01-01

    Full Text Available A study directed towards exploring the temperature-dependent reactivity of the chlorine atoms of 2,4,6-trichloro-s-triazine (TCT in the nucleophilic displacement reaction, allowed a facile replacement of its chlorine atoms in succession with (i N-amino methyl substituted isatin-3-hydrazones, (ii N1-substituted-4-amino benzene sulphonamides, and (iii 8-amino-4-oxo-N-benzyl-azacarbazole to produce the corresponding 2,4,6-trisubstituted-s-triazine, namely; 2-(N-amino methyl substituted isatin-3-hydrazinyl-4-(N1-substituted-4′-amino benzenesulfonamidyl-6-(8′-amino-4′-oxo-N-benzylazacarbazolyl-1,3,5-triazine derivatives in acceptable yields. The compounds prepared were further evaluated for their antibacterial activity against E. coli and B. subtilis and antifungal activities against A. niger and A. flavus, and some of them showed promising activity profile.

  5. BENZYLATION AND CHARACTERIZATION OF COLD NAOH/UREA PRE-SWELLED BAMBOO

    Directory of Open Access Journals (Sweden)

    Ming-Fei Li,

    2012-02-01

    Full Text Available Ball-milled bamboo was pre-swelled with a cold aqueous solution of NaOH and urea, and then reacted directly with benzyl chloride to synthesize benzylated bamboo. The effects of the molar ratio of benzyl chloride to OH groups in the bamboo (1 to 4, the reaction temperature (70 to 110 °C, and the reaction time (2 to 8 h on both the product yield and the degree of substitution (DS were evaluated. Yields between 67.6 and 94.0% and DS between 0.31 and 0.74 of the benzylated bamboo were obtained under such conditions. The incorporation of benzyl groups was evidenced by FT-IR and CP/MAS 13C-NMR spectroscopy. It was found that the crystalline structure of the native ball-milled bamboo was markedly damaged after modification. In addition, the benzylated bamboo was subjected to thermal degradation at a high temperature with an increase in substitution. It was suggested that the benzylated bamboo with a low crystallinity as well as large non-polar groups is promising as a filler for use in the composite material industry.

  6. Wheat bran valorisation: Towards photocatalytic nanomaterials for benzyl alcohol photo-oxidation.

    Science.gov (United States)

    Ouyang, Weiyi; Reina, Jose M; Kuna, Ewelina; Yepez, Alfonso; Balu, Alina M; Romero, Antonio A; Colmenares, Juan Carlos; Luque, Rafael

    2016-07-13

    In this work, we have successfully synthesized a set of titania photocatalytic nanocomposites by the incorporation of different TiO2 content on wheat bran residues. The obtained catalysts were characterized by different techniques including UV-Vis spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Transmission Electron Microscopy (TEM) while their photocatalytic activity was investigated in the oxidation of benzyl alcohol under UV light irradiation. Benzaldehyde yields were ca. 20%, with conversion in the systems of ca. 33% of benzyl alcohol by using 10%Ti-Bran catalyst, as compared to 33% yield to the target product (quantitative conversion of benzyl alcohol) using commercial pure TiO2 (P-25). The photocatalytic activity results indicate that designed waste-derived nanomaterials with low TiO2 content can efficiently photocatalyze the conversion of benzyl alcohol with relative high selectivity towards benzaldehyde.

  7. The Influence of the 1-(3-Trifluoromethyl-Benzyl)-1H-Pyrazole-4-yl Moiety on the Adenosine Receptors Affinity Profile of Pyrazolo[4,3-e][1,2,4]Triazolo[1,5-c]Pyrimidine Derivatives.

    Science.gov (United States)

    Federico, Stephanie; Redenti, Sara; Sturlese, Mattia; Ciancetta, Antonella; Kachler, Sonja; Klotz, Karl-Norbert; Cacciari, Barbara; Moro, Stefano; Spalluto, Giampiero

    2015-01-01

    A new series of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine (PTP) derivatives has been developed in order to explore their affinity and selectivity profile at the four adenosine receptor subtypes. In particular, the PTP scaffold was conjugated at the C2 position with the 1-(3-trifluoromethyl-benzyl)-1H-pyrazole, a group believed to confer potency and selectivity toward the human (h) A2B adenosine receptor (AR) to the xanthine ligand 8-(1-(3-(trifluoromethyl)benzyl)-1H-pyrazol-4-yl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (CVT 6975). Interestingly, the synthesized compounds turned out to be inactive at the hA2B AR but they displayed affinity at the hA3 AR in the nanomolar range. The best compound of the series (6) shows both high affinity (hA3 AR Ki = 11 nM) and selectivity (A1/A3 and A2A/A3 > 9090; A2B/A3 > 909) at the hA3 AR. To better rationalize these results, a molecular docking study on the four AR subtypes was performed for all the synthesized compounds. In addition, CTV 6975 and two close analogues have been subjected to the same molecular docking protocol to investigate the role of the 1-(3-trifluoromethyl-benzyl)-1H-pyrazole on the binding at the four ARs.

  8. 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.

  9. 6-Methylpurine derived sugar modified nucleosides: Synthesis and evaluation of their substrate activity with purine nucleoside phosphorylases.

    Science.gov (United States)

    Hassan, Abdalla E A; Abou-Elkhair, Reham A I; Parker, William B; Allan, Paula W; Secrist, John A

    2016-04-01

    6-Methylpurine (MeP) is cytotoxic adenine analog that does not exhibit selectivity when administered systemically, and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli PNP. The prototype MeP releasing prodrug, 9-(β-d-ribofuranosyl)-6-methylpurine, MeP-dR has demonstrated good activity against tumors expressing E. coli PNP, but its antitumor activity is limited due to toxicity resulting from the generation of MeP from gut bacteria. Therefore, we have embarked on a medicinal chemistry program to identify non-toxic MeP prodrugs that could be used in conjunction with E. coli PNP. In this work, we report on the synthesis of 9-(6-deoxy-β-d-allofuranosyl)-6-methylpurine (3) and 9-(6-deoxy-5-C-methyl-β-d-ribo-hexofuranosyl)-6-methylpurine (4), and the evaluation of their substrate activity with several phosphorylases. The glycosyl donors; 1,2-di-O-acetyl-3,5-di-O-benzyl-α-d-allofuranose (10) and 1-O-acetyl-3-O-benzyl-2,5-di-O-benzoyl-6-deoxy-5-C-methyl-β-d-ribohexofuran-ose (15) were prepared from 1,2:5,6-di-O-isopropylidine-α-d-glucofuranose in 9 and 11 steps, respectively. Coupling of 10 and 15 with silylated 6-methylpurine under Vorbrüggen glycosylation conditions followed conventional deprotection of the hydroxyl groups furnished 5'-C-methylated-6-methylpurine nucleosides 3 and 4, respectively. Unlike 9-(6-deoxy-α-l-talo-furanosyl)-6-methylpurine, which showed good substrate activity with E. coli PNP mutant (M64V), the β-d-allo-furanosyl derivative 3 and the 5'-di-C-methyl derivative 4 were poor substrates for all tested glycosidic bond cleavage enzymes.

  10. Study of selected benzyl azides by UV photoelectron spectroscopy and mass spectrometry

    Science.gov (United States)

    Pinto, R. M.; Olariu, R. I.; Lameiras, J.; Martins, F. T.; Dias, A. A.; Langley, G. J.; Rodrigues, P.; Maycock, C. D.; Santos, J. P.; Duarte, M. F.; Fernandez, M. T.; Costa, M. L.

    2010-09-01

    Benzyl azide and the three methylbenzyl azides were synthesized and characterized by mass spectrometry (MS) and ultraviolet photoelectron spectroscopy (UVPES). The electron ionization fragmentation mechanisms for benzyl azide and their methyl derivatives were studied by accurate mass measurements and linked scans at constant B/ E. For benzyl azide, in order to clarify the fragmentation mechanism, labelling experiments were performed. From the mass analysis of methylbenzyl azides isomers it was possible to differentiate the isomers ortho, meta and para. The abundance and nature of the ions resulting from the molecular ion fragmentation, for the three distinct isomers of substituted benzyl azides, were rationalized in terms of the electronic properties of the substituent. Concerning the para-isomer, IRC calculations were performed at UHF/6-31G(d) level. The photoionization study of benzyl azide, with He(I) radiation, revealed five bands in the 8-21 eV ionization energies region. From every photoelectron spectrum of methylbenzyl azides isomers it has been identified seven bands, on the same range as the benzyl azide. Interpretation of the photoelectron spectra was accomplished applying Koopmans' theorem to the SCF orbital energies obtained at HF/6-311++G(d, p) level.

  11. 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...

  12. Synthesis, Anticancer and Antibacterial Activity of Salinomycin N-Benzyl Amides

    Directory of Open Access Journals (Sweden)

    Michał Antoszczak

    2014-11-01

    Full Text Available 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.

  13. 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.

  14. Evaluation of (Z)-2-((1-benzyl-1H-indol-3-yl)methylene)-quinuclidin-3-one analogues as novel, high affinity ligands for CB1 and CB2 cannabinoid receptors.

    Science.gov (United States)

    Madadi, Nikhil Reddy; Penthala, Narsimha Reddy; Brents, Lisa K; Ford, Benjamin M; Prather, Paul L; Crooks, Peter A

    2013-04-01

    A small library of N-benzyl indolequinuclidinone (IQD) analogs has been identified as a novel class of cannabinoid ligands. The affinity and selectivity of these IQDs for the two established cannabinoid receptor subtypes, CB1 and CB2, was evaluated. Compounds 8 (R=R(2)=H, R(1)=F) and 13 (R=COOCH3, R(1)=R(2)=H) exhibited high affinity for CB2 receptors with Ki values of 1.33 and 2.50 nM, respectively, and had lower affinities for the CB1 receptor (Ki values of 9.23 and 85.7 nM, respectively). Compound 13 had the highest selectivity of all the compounds examined, and represents a potent cannabinoid ligand with 34-times greater selectivity for CB2R over CB1R. These findings are significant for future drug development, given recent reports demonstrating beneficial use of cannabinoid ligands in a wide variety of human disease states including drug abuse, depression, schizophrenia, inflammation, chronic pain, obesity, osteoporosis and cancer.

  15. 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.

  16. Synthesis and Antidiabetic Evaluation of Benzothiazole Derivatives

    Energy Technology Data Exchange (ETDEWEB)

    G, Mariappan; P, Prabhat; L, Sutharson; J, Banerjee; U, Patangia; S, Nath [Himalayan Pharmacy Institute, Majhitar (India)

    2012-04-15

    A novel series of benzothiazole derivatives were synthesized and assayed in vivo to investigate their hypogly-cemic activity by streptozotocin-induced diebetic model in rat. These derivatives showed considerable biological efficacy when compared to glibenclamide, a potent and well known antidiabetic agent as a reference drug. All the compounds were effective, amongst them 3d showed more prominent activity at 100 mg/kg p.o. The experimental results are statistically significant at p<0.01 and p<0.05 level.

  17. Synthesis and evaluation of anti-tubercular activity of new dithiocarbamate sugar derivatives.

    Science.gov (United States)

    Horita, Yasuhiro; Takii, Takemasa; Kuroishi, Ryuji; Chiba, Taku; Ogawa, Kenji; Kremer, Laurent; Sato, Yasuo; Lee, YooSa; Hasegawa, Tomohiro; Onozaki, Kikuo

    2011-02-01

    The present study was undertaken to optimize the anti-tubercular activity of 2-acetamido-2-deoxy-β-D-glucopyranosyl N,N-dimethyldithiocarbamate (OCT313, Glc-NAc-DMDC), a lead compound previously reported by us. Structural modifications of OCT313 included the replacements of the DMDC group at C-1 by pyrrolidine dithiocarbamate (PDTC) and the acetyl group at C-2 by either propyl, butyl, benzyl or oleic acid groups. The antimycobacterial activities of these derivatives were evaluated against Mycobacterium tuberculosis (MTB). Glc-NAc-pyrrolidine dithiocarbamate (OCT313HK, Glc-NAc-PDTC) exhibited the most potent anti-tubercular activity with the minimal inhibitory concentration (MIC) of 6.25-12.5 μg/ml. The antibacterial activity of OCT313HK was highly specific to MTB and Mycobacterium bovis BCG, but not against Mycobacterium avium, Mycobacterium smegmatis, Staphylococcus aureus or Escherichia coli. Importantly, OCT313HK was also effective against MTB clinical isolates, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Interestingly, OCT313HK was exerted the primary bactericidal activity, and it was also exhibited the bacteriolytic activity at high concentrations. We next investigated whether the mycobacterial monooxygenase EthA, a common activator of thiocarbamide-containing anti-tubercular drugs, also activated OCT313HK. Contrary to our expectations, the anti-tubercular activity of dithiocarbamate sugar derivatives and dithiocarbamates were not dependent on ethA expression, in contrast to thiocarbamide-containing drugs. Overall, this study presents OCT313HK as a novel and potent compound against MTB, particularly promising to overcome drug resistance.

  18. Synthesis and Antidiabetic Evaluation of Benzenesulfonamide Derivatives

    Science.gov (United States)

    Hosseinzadeh, Nouraddin; Seraj, Soodeh; Bakhshi-Dezffoli, Mohamad Ebrahim; Hasani, Mohammad; Khoshneviszadeh, Mehdi; Fallah-Bonekohal, Saeed; Abdollahi, Mohammad; Foroumadi, Alireza; Shafiee, Abbas

    2013-01-01

    The complex metabolic syndrome, diabetes mellitus, is a major human health concern in the world and is estimated to affect 300 million people by the year 2025. Several drugs such as sulfonylureas and biguanides are presently available to reduce hyperglycemia in diabetes mellitus. These drugs have side effects and thus searching for a new class of compounds is essential to overcome this problems. A series of seven novel N-(4-phenylthiazol-2-yl)benzenesulfonamides derivatives were synthesized and assayed in-vivo to investigate their antidiabetic activities by streptozotocin-induced model in rat. These derivatives showed considerable biological efficacy when compared to glibenclamide, a potent and well-known antidiabetic agent, as a reference drug. Four of the compounds were effective, amongst which 13 show more prominent activity at 100 mg/Kg p.o. The experimental results are statistically significant at p < 0.05 level. PMID:24250607

  19. Synthesis and biological evaluation of formazan derivatives.

    Science.gov (United States)

    Mariappan, Gurusamy; Korim, Rejaul; Joshi, Nand Madhwa; Alam, Faruk; Hazarika, Rajib; Kumar, Deepak; Uriah, Tiewlasubon

    2010-10-01

    The formazan derivatives (FM1-FM5) were synthesized by the reaction of benzaldehyde phenylhydrazone with substituted aromatic and hetero aromatic amines. The structures of the synthesized compounds were then elucidated using UV, IR, (1)H NMR and mass spectral data. The synthesized derivatives were screened for anticonvulsant, antibacterial and antiviral activities. All the compounds showed remarkable antibacterial activity at 250 μg/ml, but FM4 and FM3 did not show any inhibition on Staphylococcus aureus and Vibriocholera, respectively. All the compounds showed significant anticonvulsant effect at 100 mg/kg p.o. and the experimental data were statistically significant at P<0.001 level. But none of the compounds was effective against Japanese encephalitis virus.

  20. Synthesis and biological evaluation of formazan derivatives

    Directory of Open Access Journals (Sweden)

    Gurusamy Mariappan

    2010-01-01

    Full Text Available The formazan derivatives (FM1-FM5 were synthesized by the reaction of benzaldehyde phenylhydrazone with substituted aromatic and hetero aromatic amines. The structures of the synthesized compounds were then elucidated using UV, IR, 1 H NMR and mass spectral data. The synthesized derivatives were screened for anticonvulsant, antibacterial and antiviral activities. All the compounds showed remarkable antibacterial activity at 250 μg/ml, but FM4 and FM3 did not show any inhibition on Staphylococcus aureus and Vibriocholera, respectively. All the compounds showed significant anticonvulsant effect at 100 mg/kg p.o. and the experimental data were statistically significant at P<0.001 level. But none of the compounds was effective against Japanese encephalitis virus.

  1. Synthesis and Antidiabetic Evaluation of Benzenesulfonamide Derivatives

    OpenAIRE

    Hosseinzadeh, Nouraddin; Seraj, Soodeh; Bakhshi-Dezffoli, Mohamad Ebrahim; Hasani, Mohammad; Khoshneviszadeh, Mehdi; Fallah-Bonekohal, Saeed; ABDOLLAHI, Mohammad; FOROUMADI, Alireza; SHAFIEE, ABBAS

    2013-01-01

    The complex metabolic syndrome, diabetes mellitus, is a major human health concern in the world and is estimated to affect 300 million people by the year 2025. Several drugs such as sulfonylureas and biguanides are presently available to reduce hyperglycemia in diabetes mellitus. These drugs have side effects and thus searching for a new class of compounds is essential to overcome this problems. A series of seven novel N-(4-phenylthiazol-2-yl)benzenesulfonamides derivatives were synthesized a...

  2. EVALUATION OF ANTIOXIDANT POTENTIAL OF PYRAZOLONE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    G. Mariappan

    2010-06-01

    Full Text Available In this article the antioxidant property of pyrazolones derivatives (PYZ1 to PYZ10 are reported. It was assessed by estimation of Malonaldehyde (MDA and 4-Hydroxyl-2-noneal (4-HNE as lipid peroxidation markers in myocardial ischemic reperfusion injury. The inhibition of lipid peroxidation was compared with the standard ascorbic acid. Among synthesized derivatives PYZ2, PYZ3, PYZ7, PYZ8, PYZ9, and PYZ10 were found to have potent antioxidant effect against MDA marker. In case of 4-HNE, PYZ4, PYZ5, PYZ6, PYZ7, PYZ8, PYZ9 and PYZ10 were found to have effective antioxidant activity and the rest of the compounds are moderately active. Comparatively PYZ7, PYZ8, PYZ9 and PYZ10 are having effective role to control both MDA and 4-HNE generation. All the experimental data were statistically significant at p<0.05 level. Interestingly, beyond its NSAID property, this study explores the protective role of pyrazolone derivatives in ischemic heart injury.

  3. Evaluation of N-benzyl-N-[11C]methyl-2- (7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC) as a novel translocator protein (18 kDa) radioligand in kainic acid-lesioned rat.

    Science.gov (United States)

    Yanamoto, Kazuhiko; Yamasaki, Tomoteru; Kumata, Katsushi; Yui, Joji; Odawara, Chika; Kawamura, Kazunori; Hatori, Akiko; Inoue, Osamu; Yamaguchi, Masatoshi; Suzuki, Kazutoshi; Zhang, Ming-Rong

    2009-11-01

    The aim of this study was to evaluate N-benzyl-N-[11C]methyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([11C]DAC) as a new translocator protein (18 kDa) [TSPO, formerly known as the peripheral-type benzodiazepine receptor (PBR)] positron emission tomography (PET) ligand in normal mice and unilateral kainic acid (KA)-lesioned rats. DAC is a derivative of AC-5216, which is a potent and selective PET ligand for the clinical investigation of TSPO. The binding affinity and selectivity of DAC for TSPO were similar to those of AC-5216, and DAC was less lipophilic than AC-5216. The distribution pattern of [11C]DAC was in agreement with TSPO distribution in rodents. No radioactive metabolite of [11C]DAC was found in the mouse brain, although it was metabolized rapidly in mouse plasma. Using small-animal PET, we examined the in vivo binding of [11C]DAC for TSPO in KA-lesioned rats. [11C]DAC and [11C]AC-5216 exhibited similar brain uptake in the lesioned and nonlesioned striatum, respectively. The binding of [11C]DAC to TSPO was increased significantly in the lesioned striatum, and [(11)C]DAC showed good contrast between the lesioned and nonlesioned striatum (the maximum ratio was about threefold). In displacement experiments, the uptake of [11C]DAC in the lesioned striatum was eventually blocked using an excess of either unlabeled DAC or PK11195 injected. [11C]DAC had high in vivo specific binding to TSPO in the injured rat brain. Therefore, [11C]DAC is a useful PET ligand for TSPO imaging, and its specific binding to TSPO is suitable as a new biomarker for brain injury.

  4. Extraction of toluene, o-xylene from heptane and benzyl alcohol from toluene with aqueous cyclodextrins

    NARCIS (Netherlands)

    Meindersma, G.W.; Schoonhoven, van T.; Kuzmanovic, B.; Haan, de A.B.

    2006-01-01

    The separation of aromatic compounds (toluene and o-xylene) from heptane and of benzyl alcohol from toluene with aqueous solutions of cyclodextrins has been experimentally investigated, because cyclodextrins and its derivatives can selectively incorporate several organic compounds, whereas the separ

  5. Synthesis and anticonvulsant activity of 1-substituted benzyl-N-substituted-1, 2, 3-triazole-4-for-mamides

    Institute of Scientific and Technical Information of China (English)

    WANG Junmin; JUN Changsoo; CHAI Kyuyun; KWAK Kyungchell; QUAN Zheshan

    2006-01-01

    Substituted benzyl azids were synthesized through the reaction of substituted benzyl chloride and sodium azid, which subsequently underwent cyclization with ethyl propiolate and amidation to give thirteen 1-substituted benzyl-N-substituted-1, 2, 3-triazole-4-formamide derivatives (3a-3m). The structure of the synthesized compounds was confirmed by IR, 1H-NMR, MS and elemental analysis. Their anticonvulsant activity against maximal electrolshock (MES) induced seizure was tested and the result showed that all these compounds possess anticonvulsant activity in different degrees. Among those, the compounds containing chloro atoms on the phenyl ring were less potent in anticonvulsant activity, while introducing one or two fluorin atoms on benzyl system increased its activity. Furthermore, their activity decreased when there was substituent on the nitrogen atom of carboxamide, and the larger the substituent, the lower the activity.

  6. A General, Simple Catalyst for Enantiospecific Cross Couplings of Benzylic Ammonium Triflates and Boronic Acids: No Phosphine Ligand Required

    Science.gov (United States)

    Basch, Corey H.; Song, Ye-Geun; Watson, Mary P.

    2014-01-01

    Highly improved conditions for the enantiospecific cross coupling of benzylic ammonium triflates with boronic acids are reported. This method relies on the use of Ni(cod)2 without ancillary phosphine or N-heterocyclic carbene ligands as catalyst. These conditions enable the coupling of new classes of boronic acids and benzylic ammonium triflates. In particular, both heteroaromatic and vinyl boronic acids are well tolerated as coupling partners. In addition, these conditions enable the use of ammonium triflates with a variety of substituents at the benzylic stereocenter. Further, naphthyl-substitution is not required on the benzylic ammonium triflate; ammonium triflates with simple aromatic substituents also undergo this coupling. Good to high yields and levels of stereochemical fidelity are observed. This new catalyst system greatly expands the utility of enantiospecific cross couplings of these amine-derived substrates for the preparation of highly enantioenriched products. PMID:25364060

  7. Highly active and reusable catalyst from Fe-Mg-hydrotalcite anionic clay for Friedel-Crafts type benzylation reactions

    Indian Academy of Sciences (India)

    Vasant R Choudhary; Rani Jha; Pankaj A Choudhari

    2005-11-01

    Fe-Mg-hydrotalcite (Mg/Fe = 3) anionic clay with or without calcination (at 200-800°C) has been used for the benzylation of toluene and other aromatic compounds by benzyl chloride. Hydrotalcite before and after its calcination was characterized for surface area, crystalline phases and basicity. Both the hydrotalcite, particularly after its use in the benzylation reaction, and the catalyst derived from it by its calcination at 200-800°C show high catalytic activity for the benzylation of toluene and other aromatic compounds. The catalytically active species present in the catalyst in its most active form are the chlorides and oxides of iron on the catalyst surface.

  8. 40 CFR 721.329 - Halogenated benzyl ester acrylate (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Halogenated benzyl ester acrylate... Specific Chemical Substances § 721.329 Halogenated benzyl ester acrylate (generic). (a) Chemical substance... halogenated benzyl ester acrylate (PMN P-90-1527) is subject to reporting under this section for...

  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. Synthesis and Insulin—sensitizing Activity of a Series of 2—Benzyl—1,3—dicarbonyl Derivatives

    Institute of Scientific and Technical Information of China (English)

    汤磊; 冯颖; 王火权; 冯颖; 杨玉社; 嵇汝运

    2003-01-01

    A series of 2-benzyl-1,3-dicabonyl derivatives was synthesized.Their insulin-sensitizing activity was evaluated in 3T3-L1 preadipocyte cells.Compounds3,26 and 27 were found to possess strong insulin-sensitizing activity in vitro and were selected for further hypoglycemic evaluation in vivo.

  11. 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.

  12. Synthesis, biological evaluation and chemometric analysis of indazole derivatives. 1,2-Disubstituted 5-nitroindazolinones, new prototypes of antichagasic drug.

    Science.gov (United States)

    Vega, María Celeste; Rolón, Miriam; Montero-Torres, Alina; Fonseca-Berzal, Cristina; Escario, José Antonio; Gómez-Barrio, Alicia; Gálvez, Jorge; Marrero-Ponce, Yovani; Arán, Vicente J

    2012-12-01

    Chagas disease chemotherapy, currently based on only two drugs, nifurtimox and benznidazole, is far from satisfactory and therefore the development of new antichagasic compounds remains an important goal. On the basis of antichagasic properties previously described for some 1,2-disubstituted 5-nitroindazolin-3-ones (21, 33) and in order to initiate the optimization of activity of this kind of compounds, we have prepared a series of related analogs (22-32, 34-38, 58 and 59) and tested in vitro these products against epimastigote forms of Trypanosoma cruzi. 2-Benzyl-1-propyl (22), 2-benzyl-1-isopropyl (23) and 2-benzyl-1-butyl (24) derivatives have shown high trypanocidal activity and low unspecific toxicity. Other indazole derivatives with different substitution patterns (1-substituted 3-alkoxy-1H-indazoles and 2-substituted 3-alkoxy-2H-indazoles), arising from the synthetic procedures used to prepare the mentioned indazolinones, have moderate to low effectiveness. The exploration of SAR information using the concept of an activity landscape has been carried out with SARANEA software. We have also searched for structural similarities between 225 known antiprotozoan drugs and compound 22. The results confirm that compounds 22-24 constitute promising leads and that 5-nitroindazolin-3-one system is a novel anti-T. cruzi scaffold which may represent an important therapeutic alternative for the treatment of Chagas disease.

  13. Enantiomeric resolution of p-toluenesulfonate of valine benzyl ester by preferential crystallizaion.

    Science.gov (United States)

    Munegumi, Toratane; Wakatsuki, Aiko; Takahashi, Yutaro

    2012-02-01

    Preferential crystallization of amino acid derivatives by seeding a pure enantiomer into racemic amino acid solutions has been studied for many years. However, few examples of valine derivatives have been reported so far. Although there have been some reports using valine hydrogen chloride with preferential crystallization, it is difficult to obtain optical isomers for valine derivatives using preferential crystallization. In this study, repeated preferential crystallization of p-toluenesulfonate valine benzyl ester with a 20% e.e. in 2-propanol gave a 94% e.e. on sonication. Sonication accelerated crystallization rate, but there was not a big difference in e.e. between with and without sonication. However, this research demonstrates the first preferential crystallization of p-toluenesulfonate of valine benzyl esters with an acceleration of crystallization using sonication.

  14. The Benzyl Moiety in a Quinoxaline-Based Scaffold Acts as a DNA Intercalation Switch.

    Science.gov (United States)

    Mahata, Tridib; Kanungo, Ajay; Ganguly, Sudakshina; Modugula, Eswar Kalyan; Choudhury, Susobhan; Pal, Samir Kumar; Basu, Gautam; Dutta, Sanjay

    2016-06-27

    Quinoxaline antibiotics intercalate dsDNA and exhibit antitumor properties. However, they are difficult to synthesize and their structural complexity impedes a clear mechanistic understanding of DNA binding. Therefore design and synthesis of minimal-intercalators, using only part of the antibiotic scaffold so as to retain the key DNA-binding property, is extremely important. Reported is a unique example of a monomeric quinoxaline derivative of a 6-nitroquinoxaline-2,3-diamine scaffold which binds dsDNA by two different modes. While benzyl derivatives bound DNA in a sequential fashion, with intercalation as the second event, nonbenzyl derivatives showed only the first binding event. The benzyl intercalation switch provides important insights about molecular architecture which control specific DNA binding modes and would be useful in designing functionally important monomeric quinoxaline DNA binders and benchmarking molecular simulations.

  15. Synthesis and antitubercular evaluation of 7-chloro-4-alkoxyquinoline derivatives

    Directory of Open Access Journals (Sweden)

    Marcelle de Lima Ferreira Bispo

    2015-02-01

    Full Text Available A series of eight 7-chloro-4-alkoxyquinoline derivatives (2a-h have been synthesized and their in vitro (antimycobacterial activity against Mycobacterium tuberculosis was evaluated.  Furthermore, all the active compounds were selected for evaluation of their cytotoxicities against the human hepatoma (HepG2 and the relative selectivity (selective index of these compounds against M. tuberculosis compared to HepG2 was calculated based on MLD50/MIC ratios.  These biological results have been compared to a series of 7-chloro-4-aminoquinoline derivatives 1a-i, previously identified by our research group with the aim to provide important information about the structure-activity relationship of quinoline derivatives.

  16. Synthesis and Cytotoxicity Evaluation of Naphthalimide Derived N-Mustards

    Directory of Open Access Journals (Sweden)

    Qinghua Lou

    2014-06-01

    Full Text Available A series of N-mustards, which was conjugated to mono- or bis-naphthalimides with a flexible amine link, were synthesized and evaluated for cytotoxicity against five cancer cell lines (HCT-116, PC-3, U87 MG, Hep G2 and SK-OV-3. Several compounds displayed better activities than the control compound amonafide. Further evaluations by fluorescence spectroscopy studies and DNA-interstrand cross-linking assays revealed that the derivatives showed both alkylating and intercalating properties. Among the derivatives, the bis-naphthalimide N-mustard derivative 11b was found to exhibit the highest cytotoxic activity and DNA cross-linking ability. Both 11b and 7b induce HCT-116 cell apoptosis by S phase arrest.

  17. Radiohalogenated thienylethylamine derivatives for evaluating local cerebral blood flow

    Science.gov (United States)

    Goodman, Mark M.; Knapp, Jr., Furn F.

    1990-01-01

    Radiopharmaceuticals useful in brain imaging comprising radiohalogenated thienylethylamine derivatives. The compounds are 5-halo-thiophene-2-isopropyl amines able to cross the blood-brain barrier and be retained for a sufficient length of time to allow the evaluation or regional blood flow by radioimaging of the brain.

  18. Bioassays for evaluation of medical products derived from bacterial toxins.

    Science.gov (United States)

    Sesardic, Thea

    2012-06-01

    Bioassays play central role in evaluation of biological products and those derived from bacterial toxins often rely exclusively on in vivo models for assurance of safety and potency. This chapter reviews existing regulatory approved methods designed to provide information on potency and safety of complex biological medicines with an insight into strategies considered for alternative procedures.

  19. Evaluation of Consumer Satisfaction with Information Derived from Neuropsychological Assessment.

    Science.gov (United States)

    Benedict, Ralph H. B.; Horton, Arthur MacNeill, Jr.

    1991-01-01

    The utility of information derived from a consumer satisfaction questionnaire was demonstrated via an analysis of feedback from 22 referring health professionals (21 physicians and 1 clinical psychologist) who replied to questions about their satisfaction with neuropsychological evaluation reports. The questionnaire used was the Neuropsychology…

  20. Synthesis, QSAR and anticandidal evaluation of 1,2,3-triazoles derived from naturally bioactive scaffolds.

    Science.gov (United States)

    Irfan, Mohammad; Aneja, Babita; Yadava, Umesh; Khan, Shabana I; Manzoor, Nikhat; Daniliuc, Constantin G; Abid, Mohammad

    2015-03-26

    In the present study, we used eight natural precursors (1a-h) with most of them having promising antimicrobial activities and synthesised their novel 1,2,3-triazole derivatives (3a-h). In the reaction sequences, the precursor compounds (1a-h) were converted to their respective alkyne (2a-h) followed by addition of benzyl azide freshly prepared by the reaction of benzyl bromide with sodium azide using [3 + 2] azide-alkyne cycloaddition strategy. Structural elucidation of all the triazole derivatives was done using FT-IR, (1)H, (13)C NMR, mass and elemental analysis techniques. The single crystal X-ray diffraction for 3d was also recorded. The result of in vitro anticandidal activity performed against three different strains of Candida showed that compound 3e was found superior/comparable to fluconazole (FLC) with IC50 values of 0.044 μg/mL against Candida albicans (ATCC 90028), 12.022 μg/mL against Candida glabrata (ATCC 90030), and 3.60 μg/mL against Candida tropicalis (ATCC 750). Moreover, at their IC50 values, compounds 3e and 3h showed <5% hemolysis which indicates the non-toxic behaviour of these inhibitors. Cytotoxicity assay was also performed on VERO cell line and all the derivatives were found non-toxic up to the concentration of 10.0 μg/mL. The in silico technique of 3D-QSAR was applied to establish structure activity relationship of the synthesized compounds. The results reveal the molecular fragments that play an essential role in improving the anticandidal activity.

  1. Oxidation of N-benzyl groups

    Institute of Scientific and Technical Information of China (English)

    QIU, Wen-Ge; CHEN, Shu-Sen; YU, Yong-Zhong

    2000-01-01

    The oxidative reactivity of 2,6,8, 12-tetraacetyl-4, 10- dibenzyl-2,4,6,8,10,12-hexaazatetracyclo[5.5.0.05,9. 03,11] dodecane (3) in several conditions was studied. It was found that the N-benzyl groups in compound 3 could be oxidized to benzoyl groups byCr(Ⅳ) reagents, and could be removed by cerium ammonium nitrate (CAN), meanwhile nttroamine prooducts were given.

  2. Automatic derivation and evaluation of vibrational coupled cluster theory equations

    Science.gov (United States)

    Seidler, Peter; Christiansen, Ove

    2009-12-01

    A scheme for automatic derivation and evaluation of the expressions occurring in vibrational coupled cluster theory is introduced. The method is based on a Baker-Campbell-Hausdorff expansion of the similarity transformed Hamiltonian and is general both with respect to the excitation level in the parameter space and the mode coupling level in the Hamiltonian. In addition to deriving general expressions, intermediates that lower the computational scaling are automatically detected. The final equations are then evaluated. Due to the commutator based nature of the algorithm, it is also applicable to the evaluation of quantities needed for response theory. Different aspects of the theory and implementation are illustrated by calculations on model systems. Furthermore, all fundamental excitation energies of ethylene oxide are calculated.

  3. Solvent effects in the reaction between piperazine and benzyl bromide

    Indian Academy of Sciences (India)

    S Ranga Reddy; P Manikyamba

    2007-11-01

    The reaction between piperazine and benzyl bromide was studied conductometrically and the second order rate constants were computed. These rate constants determined in 12 different protic and aprotic solvents indicate that the rate of the reaction is influenced by electrophilicity (), hydrogen bond donor ability () and dipolarity/polarizability (*) of the solvent. The LSER derived from the statistical analysis indicates that the transition state is more solvated than the reactants due to hydrogen bond donation and polarizability of the solvent while the reactant is more solvated than the transition state due to electrophilicity of the solvent. Study of the reaction in methanol, dimethyl formamide mixtures suggests that the rate is maximum when dipolar interactions between the two solvents are maximum.

  4. Synthesis of benzyl cinnamate by enzymatic esterification of cinnamic acid.

    Science.gov (United States)

    Wang, Yun; Zhang, Dong-Hao; Chen, Na; Zhi, Gao-Ying

    2015-12-01

    In this study, lipase catalysis was successfully applied in synthesis of benzyl cinnamate through esterification of cinnamic acid with benzyl alcohol. Lipozyme TLIM was found to be more efficient for catalyzing this reaction than Novozym 435. In order to increase the yield of benzyl cinnamate, several media, including acetone, trichloromethane, methylbenzene, and isooctane, were used in this reaction. The reaction showed a high yield using isooctane as medium. Furthermore, the effects of several parameters such as water activity, reaction temperature, etc, on this reaction were analyzed. It was pointed out that too much benzyl alcohol would inhibit lipase activity. Under the optimum conditions, lipase-catalyzed synthesis of benzyl cinnamate gave a maximum yield of 97.3%. Besides, reusable experiment of enzyme demonstrated that Lipozyme TLIM retained 63% of its initial activity after three cycles. These results were of general interest for developing industrial processes for the preparation of benzyl cinnamate.

  5. Synthesis, antimicrobial evaluation and QSAR studies of gallic acid derivatives

    Directory of Open Access Journals (Sweden)

    Anurag Khatkar

    2017-05-01

    Full Text Available A series of gallic acid derivatives (1–33 was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were evaluated in vitro for their antimicrobial activity against different Gram positive and Gram negative bacterial and fungal strains by the tube dilution method. Results of antimicrobial screening indicated that compound 6 was the most active antimicrobial agent (pMICam = 1.92 μM/mL. The results of QSAR studies demonstrated that antibacterial, antifungal and overall antimicrobial activities of synthesized gallic acid derivatives were governed by the electronic parameters, cosmic total energy (Cos E. and nuclear energy (Nu. E..

  6. Evaluation of new rosin derivatives for pharmaceutical coating.

    Science.gov (United States)

    Satturwar, P M; Fulzele, S V; Panyam, J; Mandaogade, P M; Mundhada, D R; Gogte, B B; Labhasetwar, V; Dorle, A K

    2004-02-11

    Rosin and Rosin-based polymers have diversified drug delivery applications achieving sustained/controlled release profiles. In this manuscript, two new Rosin derivatives were synthesized and evaluated for physicochemical properties, molecular weight, polydispersity and glass transition temperature. Plasticizer-free films prepared by solvent evaporation were tested for surface morphology, water vapour transmission and mechanical properties (tensile strength, percent elongation and modulus of elasticity). The films showed low tensile strength and high percent elongation values achieving smooth and uniform surface. The derivatives were further characterized for film coating by evaluating the release of a model drug (diclofenac sodium) from pellets coated with the rosin derivatives as retarding membrane. Drug release was sustained up to 10 h due to 10% (w/w) coat built up with the new rosin derivatives. Increase in coat-built-up further facilitated sustained release from coated forms. Film coating could be achieved without agglomeration of the pellets within a reasonable operating time. The present study proposes novel film forming materials with potential use in sustained drug delivery.

  7. Synthesis and anticancer evaluation of alpha-lipoic acid derivatives.

    Science.gov (United States)

    Zhang, Shi-Jie; Ge, Qiu-Fu; Guo, Dian-Wu; Hu, Wei-Xiao; Liu, Hua-Zhang

    2010-05-15

    alpha-Lipoic acid derivatives were synthesized and evaluated for their in vitro anticancer activities against NCI-460, HO-8910, KB, BEL-7402, and PC-3 cell lines. The results, for most compounds exhibited dose-dependent inhibitory property and several compounds had good inhibitions at the dose of 100 microg/mL. Compound 17 m was further selected for in vivo evaluation against S180 xenograft in ICR mice, which had 24.7% tumor-weight inhibition through intragastric administration of 200mg/kg of body weight. Moreover, the LD(50) in mice for 17 m through ig exceeded 1000 mg/kg of body weight.

  8. Polycyclic aromatic hydrocarbon (PAH) formation from benzyl radicals: a reaction kinetics study.

    Science.gov (United States)

    Sinha, Sourab; Raj, Abhijeet

    2016-03-21

    The role of resonantly stabilized radicals such as propargyl, cyclopentadienyl and benzyl in the formation of aromatic hydrocarbons such as benzene and naphthalene in the high temperature environments has been long known. In this work, the possibility of benzyl recombination to form three-ring aromatics, phenanthrene and anthracene, is explored. A reaction mechanism for it is developed, where reaction energetics are calculated using density functional theory (B3LYP functional with 6-311++G(d,p) basis set) and CBS-QB3, while temperature-dependent reaction kinetics are evaluated using transition state theory. The mechanism begins with barrierless formation of bibenzyl from two benzyl radicals with the release of 283.2 kJ mol(-1) of reaction energy. The further reactions involve H-abstraction by a H atom, H-desorption, H-migration, and ring closure to gain aromaticity. Through mechanism and rate of production analyses, the important reactions leading to phenanthrene and anthracene formation are determined. Phenanthrene is found to be the major product at high temperatures. Premixed laminar flame simulations are carried out by including the proposed reactions for phenanthrene formation from benzyl radicals and compared to experimentally observed species profiles to understand their effects on species concentrations.

  9. Evolution of plant defense mechanisms. Relationships of phenylcoumaran benzylic ether reductases to pinoresinol-lariciresinol and isoflavone reductases.

    Science.gov (United States)

    Gang, D R; Kasahara, H; Xia, Z Q; Vander Mijnsbrugge, K; Bauw, G; Boerjan, W; Van Montagu, M; Davin, L B; Lewis, N G

    1999-03-12

    Pinoresinol-lariciresinol and isoflavone reductase classes are phylogenetically related, as is a third, the so-called "isoflavone reductase homologs." This study establishes the first known catalytic function for the latter, as being able to engender the NADPH-dependent reduction of phenylcoumaran benzylic ethers. Accordingly, all three reductase classes are involved in the biosynthesis of important and related phenylpropanoid-derived plant defense compounds. In this investigation, the phenylcoumaran benzylic ether reductase from the gymnosperm, Pinus taeda, was cloned, with the recombinant protein heterologously expressed in Escherichia coli. The purified enzyme reduces the benzylic ether functionalities of both dehydrodiconiferyl alcohol and dihydrodehydrodiconiferyl alcohol, with a higher affinity for the former, as measured by apparent Km and Vmax values and observed kinetic 3H-isotope effects. It abstracts the 4R-hydride of the required NADPH cofactor in a manner analogous to that of the pinoresinol-lariciresinol reductases and isoflavone reductases. A similar catalytic function was observed for the corresponding recombinant reductase whose gene was cloned from the angiosperm, Populus trichocarpa. Interestingly, both pinoresinol-lariciresinol reductases and isoflavone reductases catalyze enantiospecific conversions, whereas the phenylcoumaran benzylic ether reductase only shows regiospecific discrimination. A possible evolutionary relationship among the three reductase classes is proposed, based on the supposition that phenylcoumaran benzylic ether reductases represent the progenitors of pinoresinol-lariciresinol and isoflavone reductases.

  10. Efficient desymmetrization of 4,6-di-O-benzyl-myo-inositol by Lipozyme TL-IM.

    Science.gov (United States)

    Vasconcelos, Marcela G; Briggs, Raissa H C; Aguiar, Lucia C S; Freire, Denise M G; Simas, Alessandro B C

    2014-03-11

    The enantioselective enzymatic desymmetrization of 4,6-di-O-benzyl-myo-inositol, a myo-inositol derivative, was effectively catalyzed by Thermomyces lanuginosus lipase (TL-IM). The product 1D-1-O-acetyl-4,6-di-O-benzyl-myo-inositol, a useful precursor to inositol phosphates, was obtained in excellent yield and enantiomeric excess. Through the investigation of the effects of solvent, biocatalyst load, and temperature, a more economical procedure resulted. The feasibility of biocatalyst reuse was also shown.

  11. Ir/Sn dual-reagent catalysis towards highly selective alkylation of arenes and heteroarenes with benzyl alcohols

    Indian Academy of Sciences (India)

    Sujit Roy; Susmita Podder; Joyanta Choudhury

    2008-09-01

    A catalytic combination of [Ir(COD)Cl]2-SnCl4 efficiently promotes the reactions of arenes and heteroarenes with 1°/2°/3° benzyl alcohols as the alkylating agents to afford the corresponding diarylmethane and triarylmethane derivatives in high yields. The scope and limitation of the reaction with respect to catalyst and substrates variation has been studied in detail.

  12. The Synthesis and Evaluation of Arctigenin Amino Acid Ester Derivatives.

    Science.gov (United States)

    Cai, En-Bo; Yang, Li-Min; Jia, Cai-Xia; Zhang, Wei-Yuan; Zhao, Yan; Li, Wei; Song, Xing-Zhuo; Zheng, Man-Ling

    2016-10-01

    The use of arctigenin (ARG), a traditional medicine with many pharmacological activities, has been restricted due to its poor solubility in water. Five amino acid derivatives of ARG have been synthesized using glycine, o-alanine, valine, leucine, and isoleucine, which have t-butyloxy carbonyl (BOC) as a protective group. In this study, we examined the effects of removing these protective groups. The results showed that the amino acid derivatives have better solubility and nitrite-clearing ability than ARG. Among the compounds tested, the amino acid derivatives without protective group were the best. Based on these results, ARG and its two amino acid derivatives without protective group (ARG8, ARG10) were selected to evaluate their anti-tumor activity in vivo at a dosage of 40 mg/kg. The results indicated that ARG8 and ARG10 both exhibit more anti-tumor activity than ARG in H22 tumor-bearing mice. The tumor inhibition rates of ARG8 and ARG10 were 69.27 and 43.58%, which was much higher than ARG. Furthermore, the mice treated with these compounds exhibited less damage to the liver, kidney and immune organs compared with the positive group. Furthermore, ARG8 and ARG10 improved the serum cytokine levels significantly compared to ARG. In brief, this study provides a method to improve the water solubility of drugs, and we also provide a reference basis for new drug development.

  13. The arylpiperazine derivatives N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide and N-benzyl-4-(2-diphenyl)-1-piperazinehexanamide exert a long-lasting inhibition of human serotonin 5-HT7 receptor binding and cAMP signaling.

    Science.gov (United States)

    Atanes, Patricio; Lacivita, Enza; Rodríguez, Javier; Brea, José; Burgueño, Javier; Vela, José Miguel; Cadavid, María Isabel; Loza, María Isabel; Leopoldo, Marcello; Castro, Marián

    2013-12-01

    We performed a detailed in vitro pharmacological characterization of two arylpiperazine derivatives, compound N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211) previously identified as a high-affinity brain penetrant ligand for 5-hydroxytryptamine (serotonin) type 7 (5-HT7) receptors, and its analog N-benzyl-4-(2-diphenyl)-1-piperazinehexanamide (MEL-9). Both ligands exhibited competitive displacement of [(3)H]-(2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine ([(3)H]-SB-269970) radioligand binding and insurmountable antagonism of 5-carboxamidotryptamine (5-CT)-stimulated cyclic adenosine monophosphate (cAMP) signaling in human embryonic kidney (HEK293) cells stably expressing human 5-HT7 receptors. They also inhibited forskolin-stimulated adenylate cyclase activity in 5-HT7-expressing HEK293 cells but not in the parental cell line. The compounds elicited long-lasting (at least 24 h) concentration-dependent inhibition of radioligand binding at 5-HT7-binding sites in whole-cell radioligand binding assays, after pretreatment of the cells with the compounds and subsequent compound removal. In cAMP assays, pretreatment of cells with the compounds rendered 5-HT7 receptors unresponsive to 5-CT and also rendered 5-HT7-expressing HEK293 cells unresponsive to forskolin. Compound 1-(2-biphenyl)piperazine (RA-7), a known active metabolite of LP-211 present in vivo, was able to partially inhibit 5-HT7 radioligand binding in a long-lasting irreversible manner. Hence, LP-211 and MEL-9 were identified as high-affinity long-acting inhibitors of human 5-HT7 receptor binding and function in cell lines. The detailed in vitro characterization of these two pharmacological tools targeting 5-HT7 receptors may benefit the study of 5-HT7 receptor function and it may lead to the development of novel selective pharmacological tools with defined functional properties at 5-HT7 receptors.

  14. Evaluation of hail suppression programme effectiveness using radar derived parameters

    Science.gov (United States)

    Tani, Satyanarayana; Paulitsch, Helmut; Teschl, Reinhard; Süsser-Rechberger, Barbara

    2016-04-01

    The objective of this study is evaluating "the operational hail suppression programme" in the province of Styria, Austria "for the year 2015". For the evaluation purpose the HAILSYS software tool was developed by integrating single polarization C-band weather radar data, aircraft trajectory, radiosonde freezing level data, hail events and crop damages information from the ground. The hail related radar derived parameters are: hail mass aloft, hail mass flux, probability of hail, vertical integrated hail mass, hail kinetic energy flux, and storm severity index. The spatial maps of hail kinetic energy and hail mass were developed to evaluate the seeding effect. The time history plots of vertical integrated hail mass, hail mass aloft and the probability of hail are drawn over an entire cell lifetime. The sensitivity and variation of radar hail parameters over time and associated changes due to cloud seeding will be presented.

  15. 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.

  16. Benzylic oxidation catalyzed by dirhodium(II,III) caprolactamate.

    Science.gov (United States)

    Catino, Arthur J; Nichols, Jason M; Choi, Hojae; Gottipamula, Sidhartha; Doyle, Michael P

    2005-11-10

    [reaction: see text] Dirhodium caprolactamate [Rh2(cap)4] is an effective catalyst for benzylic oxidation with tert-butyl hydroperoxide (TBHP) under mild conditions. Sodium bicarbonate is the optimal base additive for substrate conversion. Benzylic carbonyl compounds are readily obtained, and a formal synthesis of palmarumycin CP2 using this methodology is described.

  17. Whole cells in enantioselective reduction of benzyl acetoacetate

    Directory of Open Access Journals (Sweden)

    Joyce Benzaquem Ribeiro

    2014-09-01

    Full Text Available The β-ketoester benzyl acetoacetate was enantioselectively reduced to benzyl (S-3-hydroxybutanoate by seven microorganism species. The best result using free cells was obtained with the yeast Hansenula sp., which furnished 97% ee and 85% of conversion within 24 h. After immobilization in calcium alginate spheres, K.marxianus showed to be more stable after 2 cycles of reaction.

  18. Synthesis, characterization and biological evaluation of thiazolopyrimidine derivatives

    Indian Academy of Sciences (India)

    H Nagarajaiah; I M Khazi; Noor Shahina Begum

    2012-07-01

    Different substituted diesters of thiazolopyrimidine were prepared by the treatment of 3,4 dihydropyrimidine2-thione with -haloesters using ethanol under reflux condition affording 71-85% yield. IR, 1HNMR, 13CNMR and elemental analyses were used for the characterization of these compounds. The crystal and molecular structure of one of the product, 5-phenyl-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidine-2,6-dicarboxylic acid diethyl ester (3e) was verified by single crystal X-ray diffraction method. The antimicrobial activity was evaluated against four bacterial strains and one fungal species. Few of the derivatives exhibited antibacterial and antifungal activities.

  19. Evaluation of ascorbic acid in protecting labile folic acid derivatives.

    OpenAIRE

    1983-01-01

    The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu ga...

  20. Accurate derivative evaluation for any Grad–Shafranov solver

    Energy Technology Data Exchange (ETDEWEB)

    Ricketson, L.F. [Courant Institute of Mathematical Sciences, New York University, New York, NY 10012 (United States); Cerfon, A.J., E-mail: cerfon@cims.nyu.edu [Courant Institute of Mathematical Sciences, New York University, New York, NY 10012 (United States); Rachh, M. [Courant Institute of Mathematical Sciences, New York University, New York, NY 10012 (United States); Freidberg, J.P. [Plasma Science and Fusion Center, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2016-01-15

    We present a numerical scheme that can be combined with any fixed boundary finite element based Poisson or Grad–Shafranov solver to compute the first and second partial derivatives of the solution to these equations with the same order of convergence as the solution itself. At the heart of our scheme is an efficient and accurate computation of the Dirichlet to Neumann map through the evaluation of a singular volume integral and the solution to a Fredholm integral equation of the second kind. Our numerical method is particularly useful for magnetic confinement fusion simulations, since it allows the evaluation of quantities such as the magnetic field, the parallel current density and the magnetic curvature with much higher accuracy than has been previously feasible on the affordable coarse grids that are usually implemented.

  1. Evaluation of flavonols and derivatives as human cathepsin B inhibitor.

    Science.gov (United States)

    Ramalho, Suelem D; de Sousa, Lorena R F; Burger, Marcela C M; Lima, Maria Inês S; da Silva, M Fátima das G F; Fernandes, João B; Vieira, Paulo C

    2015-01-01

    Cathepsin B (catB) is a cysteine protease involved in tumour progression and represents a potential therapeutic target in cancer. Among the 15 evaluated extracts from cerrado biome, Myrcia lingua Berg. (Myrtaceae) extract demonstrated to be a source of compounds with potential to inhibit catB. Using bioactivity-guided fractionation, we have found flavonols as inhibitors and also some other derivatives were obtained. From the evaluated compounds, myricetin (5) and quercetin (6) showed the most promising results with IC50 of 4.9 and 8.2 μM, respectively, and mode of inhibition as uncompetitive on catB. The results demonstrated polyhydroxylated flavonols as promising inhibitors of catB.

  2. Synthesis and Insecticidal Activity of Spinosyns with C9-O-Benzyl Bioisosteres in Place of the 2',3',4'-Tri-O-methyl Rhamnose.

    Science.gov (United States)

    Oliver, M Paige; Crouse, Gary D; Demeter, David A; Sparks, Thomas C

    2015-06-17

    The spinosyns are fermentation-derived natural products active against a wide range of insect pests. They are structurally complex, consisting of two sugars (forosamine and rhamnose) coupled to a macrocyclic tetracycle. Removal of the rhamnose sugar results in a >100-fold reduction in insecticidal activity. C9-O-benzyl analogues of spinosyn D were synthesized to determine if the 2',3',4'-tri-O-methyl rhamnose moiety could be replaced with a simpler, synthetic bioisostere. Insecticidal activity was evaluated against larvae of Spodoptera exigua (beet armyworm) and Helicoverpa zea (corn earworm). Whereas most analogues were far less active than spinosyn D, a few of the C9-O-benzyl analogues, such as 4-CN, 4-Cl, 2-isopropyl, and 3,5-diOMe, were within 3-15 times the activity of spinosyn D for larvae of S. exigua and H. zea. Thus, although not yet quite as effective, synthetic bioisosteres can substitute for the naturally occurring 2',3',4'-tri-O-methyl rhamnose moiety.

  3. Benzyl (E-3-(2-methylbenzylidenedithiocarbazate

    Directory of Open Access Journals (Sweden)

    Shang Shan

    2011-09-01

    Full Text Available The title compound, C16H16N2S2, was obtained from the condensation reaction of benzyl dithiocarbazate and 2-methylbenzaldehyde. The asymmetric unit contains two independent molecules. In both molecules, the methylphenyl ring and the dithiocarbazate fragment are located on opposite sides of the C=N bond, showing an E conformation. In each molecule, the dithiocarbazate fragment is approximately planar, the r.m.s deviations being 0.018 and 0.025 Å. The mean plane of dithiocarbazate group is oriented at dihedral angles of 7.9 (3 and 68.24 (12°, respectively, to the methylphenyl and phenyl rings in one molecule, while the corresponding angles in the other molecule are 10.9 (3 and 69.76 (16°. Intermolecular N—H...S hydrogen bonding occurs in the crystal structure to generate inversion dimers for both molecules.

  4. Evaluation of antimycobacterial activity of a sulphonamide derivative.

    Science.gov (United States)

    Agertt, Vanessa Albertina; Marques, Lenice Lorenço; Bonez, Pauline Cordenonsi; Dalmolin, Tanise Vendruscolo; Manzoni de Oliveira, Gelson Noe; de Campos, Marli Matiko Anraku

    2013-05-01

    Mycobacterial infections including Mycobacterium tuberculosis have been increasing globally. The additional prevalence of multidrug-resistant (MDR-TB) strains and extensively drug-resistant tuberculosis (XDR-TB) stimulate an urgent need for the development of new drugs for the treatment of mycobacterial infections. It is very important to test the antimicrobial activity of novel compounds because they can be used in new with antimycobacterial drug formulation. Studies have shown that Mycobacterium smegmatis can be used in Minimum Inhibitory Concentration (MIC) assays with the advantage of rapidly and safely screen anti-tubercular compounds. This paper presents an evaluation of potential mycobacteriological compounds derived from inorganic synthesis and their microbiological performance along and in conjunction with Trimethoprim. Antimicrobial activity experiments were carried out by using the microdilution technique in broth to evaluate the sensibility against M. smegmatis. MIC values were between 0.153 and 4.88 μg/ml for the compounds tested. Tests of interaction between drugs were made by the method of Fractional Inhibitory Concentration Index (FICI). The compound [Au (sulfatiazolato)(PPh3)] showed synergism FICI = 0.037 and was evaluated by isobols.

  5. Evaluation of ascorbic acid in protecting labile folic acid derivatives.

    Science.gov (United States)

    Wilson, S D; Horne, D W

    1983-11-01

    The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu gave rise to 5-formyl-H4PteGlu and 10-formyl-PteGlu. 5-Formyl-H4-PteGlu gave rise to a small amount of 10-formyl-PteGlu. 5-Methyl-H4PteGlu and PteGlu appeared stable to these conditions. These interconversions were not seen when solutions of these folate derivatives were kept at 0 degrees C in 1% ascorbate. These observations indicate that elevated temperatures are necessary for the interconversions of folates in ascorbate solutions. Assays of ascorbic acid solutions indicated the presence of formaldehyde (approximately equal to 6 mM). This was confirmed by the identification of 3,5-diacetyl-1,4-dihydrolutidine by UV, visible, and fluorescence spectroscopy and by thin-layer chromatography of chloroform extracts of the reaction mixture of ascorbic acid solutions, acetylacetone, and ammonium acetate. These results indicate that solutions of sodium ascorbate used at elevated temperatures are not suitable for extracting tissue for the subsequent assay of the individual folic acid derivatives.

  6. 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.

  7. Evaluation of labdane derivatives as potential anti-inflammatory agents.

    Science.gov (United States)

    Girón, Natalia; Pérez-Sacau, Elisa; López-Fontal, Raquel; Amaro-Luis, Juan M; Hortelano, Sonsoles; Estevez-Braun, Ana; de Las Heras, Beatriz

    2010-07-01

    In the present study, a series of labdane derivatives (2-9) were prepared from labdanediol (1) and their potential as anti-inflammatory agents were evaluated on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. All compounds were able to inhibit LPS-induced nitric oxide (NO), although compounds 1, 2, 5, 8 and 9 exhibited the most potent effects with a range of IC(50) values of 5-15 microM. Similarly to the inhibitory effects on NO release, these labdane derivatives also inhibited prostaglandin E(2) (PGE(2)) production. However, analysis of cell viability demonstrated that effects on NO release and (PGE(2)) production of compounds 1, 8 and 9 were due to citotoxicity, whereas compound 2 and 5 did not show any effect in the survival of RAW 264.7 macrophages. In addition to these in vitro data, compound 5 also showed anti-inflammatory activity in vivo, when tested in mice. They prevented the extent of swelling in the TPA-induced ear edema model and inhibited MPO activity, showing similar potency to that of the widely used anti-inflammatory drug indomethacin. These results indicate that compound 2 and in particular compound 5 might be used for the design of new anti-inflammatory agents. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  8. 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.

  9. Evaluation of antioxidant properties of monoaromatic derivatives of pulvinic acids.

    Science.gov (United States)

    Habrant, Damien; Poigny, Stéphane; Ségur-Derai, Muriel; Brunel, Yves; Heurtaux, Benoît; Le Gall, Thierry; Strehle, Axelle; Saladin, Régis; Meunier, Stéphane; Mioskowski, Charles; Wagner, Alain

    2009-04-23

    The natural mushroom pigment Norbadione A and three other pulvinic acids were shown by our group to display very efficient antioxidant properties by comparison with a collection of potent molecules including catechols, flavonoids, stilbenes, or coumarins. Despite numerous publications on robust and straightforward synthetic access to pulvinic acids by us and others, no report has been made to unravel the structure-activity relationships that govern the striking antioxidant activity. Herein is presented the synthesis of 18 diverse pulvinic acid derivatives and the study of their radical scavenging capacities by four different assays. The influence of each of the two phenyl rings, of their substituents and of the lateral chain on the antioxidant properties, was explored to reveal a simplified structure of excellent activity. These results, along with the absence of cytotoxicity, make the synthesized compounds interesting to evaluate for several biological activities and especially for anti-inflammatory effects and skin protection against UV induced oxidative stress.

  10. Synthesis, antimicrobial evaluation and QSAR studies of propionic acid derivatives

    Directory of Open Access Journals (Sweden)

    Sanjiv Kumar

    2017-02-01

    Full Text Available A series of Schiff bases (1–17 and esters (18–24 of propionic acid was synthesized in appreciable yield and characterized by physicochemical as well as spectral means. The synthesized compounds were evaluated in vitro for their antimicrobial activity against Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, Gram negative bacterium Escherichia coli and fungal strains Candida albicans and Aspergillus niger by tube dilution method. Results of antimicrobial screening indicated that besides having good antibacterial activity, the synthesized compounds also displayed appreciable antifungal activity and compound 10 emerged as the most active antifungal agent (pMICca and pMICan = 1.93. The results of QSAR studies demonstrated that antibacterial, antifungal and overall antimicrobial activities of synthesized propionic acid derivatives were governed by the topological parameters, Kier’s alpha first order shape index (κα1 and valence first order molecular connectivity index (1χv.

  11. Evaluation of natural anthracene-derived compounds as antimitotic agents.

    Science.gov (United States)

    Badria, Farid A; Ibrahim, Ahmed S

    2013-04-01

    Plants that contain anthracene-derived compounds such as anthraquinones have been reported to act as anticancer besides their use for millennia to treat constipation, but the mechanism of action is still unfolding. Therefore we pursue this study to explore a new horizon in the anticancer property of these agents with relevance to mitotic arrest. To achieve this goal, the antimitotic activity of a series of naturally occurring anthracene-derived anthraquinones including anthrone, alizarin (1,2-dihydroxyanthraquinone), quinizarin (1,4-dihydroxyanthraquinone), rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), emodin (1,6,8-trihydroxy-3-methylanthraquinone), and aloe emodin (1,8-dihydroxy-3-hydroxymethylanthraquinone) were evaluated using Allium cepa root tips. Initial results revealed that the mitosis was inhibited after 3, 6, and 24 h, respectively, of incubation with 500, 250, and 125 ppm of each compound in a dose-dependent manner. Furthermore, alizarin at 500 ppm was proved to be the most active compound to arrest the mitosis after 24 h followed by emodin, aloe emodin, rhein, and finally quinizarin. Interestingly, this inhibition of mitosis was irreversible in root tips incubated with each compound at concentration of 500 ppm but not with 250 ppm or 125 ppm, where the roots regained their normal mitotic activity after 96 h post-incubation in water. This re-evaluation of an old remedy suggests that several bioactive anthraquinones possess promising anti-mitotic activity that may have the potential to be lead compounds for the development of a new class of multifaceted natural anticancer/antimitotic agents.

  12. 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

  13. Novel routes to either racemic or enantiopure α-amino-(4-hydroxy-pyrrolidin-3-yl)acetic acid derivatives and biological evaluation of a new promising pharmacological scaffold.

    Science.gov (United States)

    Cecioni, Samy; Aouadi, Kaïss; Guiard, Julie; Parrot, Sandrine; Strazielle, Nathalie; Blondel, Sandrine; Ghersi-Egea, Jean-François; Chapelle, Christian; Denoroy, Luc; Praly, Jean-Pierre

    2015-06-15

    Cycloaddition between (+) or (-)-menthone-derived nitrones and N-benzyl-3-pyrroline afforded enantiopure spiro-fused heterocycles. The reaction occurred enantio- and diastereo-selectively on the less hindered side of the nitrone, the 3-pyrroline N-benzyl group being oriented outwards, thus controlling the configurations of three simultaneously created chiral centers. From either (+) or (-)-menthone, both enantiomeric cycloadducts were synthesized in excellent yield. Removing the chiral auxiliary and the N-benzyl group delivered a series of enantiopure 4-hydroxy-3-glycinyl-pyrrolidine derivatives in 3-5 steps and 36 to 81 overall yields. Using two other achiral nitrones, shorter routes to racemic analogues were developed. Two of the synthesized compounds markedly lowered extracellular glutamate level and modestly interacted with cannabinoid type-1 receptors. As these two neuroactive compounds were devoid of in vitro toxicity and did not cross the blood brain interface, they might represent potential pharmacological agents to target peripheral organs.

  14. 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.

  15. s-Block organometallics: analysis of ion-association and noncovalent interactions on structure and function in benzyl-based compounds.

    Science.gov (United States)

    Torvisco, Ana; Ruhlandt-Senge, Karin

    2011-12-19

    The organometallic chemistry of alkali and alkaline-earth metals has been marred by synthetic setbacks because of their high reactivity. Advances in their synthesis and a better understanding of the stabilization effects of ligands and coligands have resulted in the revolution of s-block organometallics. Among those, benzyl-based derivatives have played a key role in developing this chemistry because factors such as the ligand size, charge delocalization, and introduction of electronic parameters along with metal effects can be analyzed. This article will focus on s-block benzylates and di- and triphenylmethanide derivatives with specific emphasis on the factors that stabilize the highly reactive metal species.

  16. First Magnesium-mediated Carbonyl Benzylation in Water

    Institute of Scientific and Technical Information of China (English)

    DENG,Wei(邓维); TAN,Xiang-Hui(谭翔辉); LIU,Lei(刘磊); GUO,Qing-Xiang(郭庆祥)

    2004-01-01

    Catalyzed by AgNO3, Mg was found for the first time to be able to mediate the coupling reaction between aromatic aldehydes and benzyl bromide or chloride in water. The yields were slightly higher than the recent results for Mg-mediated allylation despite the fact that aqueous benzylation is intrinsically much harder than allylation. It was also found that the coupling reaction was chemoselective for aromatic aldehydes over aliphatic aldehydes, and chemoselective for aromatic aldehydes over aromatic ketones.

  17. Evaluating Error of LIDAR Derived dem Interpolation for Vegetation Area

    Science.gov (United States)

    Ismail, Z.; Khanan, M. F. Abdul; Omar, F. Z.; Rahman, M. Z. Abdul; Mohd Salleh, M. R.

    2016-09-01

    Light Detection and Ranging or LiDAR data is a data source for deriving digital terrain model while Digital Elevation Model or DEM is usable within Geographical Information System or GIS. The aim of this study is to evaluate the accuracy of LiDAR derived DEM generated based on different interpolation methods and slope classes. Initially, the study area is divided into three slope classes: (a) slope class one (0° - 5°), (b) slope class two (6° - 10°) and (c) slope class three (11° - 15°). Secondly, each slope class is tested using three distinctive interpolation methods: (a) Kriging, (b) Inverse Distance Weighting (IDW) and (c) Spline. Next, accuracy assessment is done based on field survey tachymetry data. The finding reveals that the overall Root Mean Square Error or RMSE for Kriging provided the lowest value of 0.727 m for both 0.5 m and 1 m spatial resolutions of oil palm area, followed by Spline with values of 0.734 m for 0.5 m spatial resolution and 0.747 m for spatial resolution of 1 m. Concurrently, IDW provided the highest RMSE value of 0.784 m for both spatial resolutions of 0.5 and 1 m. For rubber area, Spline provided the lowest RMSE value of 0.746 m for 0.5 m spatial resolution and 0.760 m for 1 m spatial resolution. The highest value of RMSE for rubber area is IDW with the value of 1.061 m for both spatial resolutions. Finally, Kriging gave the RMSE value of 0.790m for both spatial resolutions.

  18. EVALUATING ERROR OF LIDAR DERIVED DEM INTERPOLATION FOR VEGETATION AREA

    Directory of Open Access Journals (Sweden)

    Z. Ismail

    2016-09-01

    Full Text Available Light Detection and Ranging or LiDAR data is a data source for deriving digital terrain model while Digital Elevation Model or DEM is usable within Geographical Information System or GIS. The aim of this study is to evaluate the accuracy of LiDAR derived DEM generated based on different interpolation methods and slope classes. Initially, the study area is divided into three slope classes: (a slope class one (0° – 5°, (b slope class two (6° – 10° and (c slope class three (11° – 15°. Secondly, each slope class is tested using three distinctive interpolation methods: (a Kriging, (b Inverse Distance Weighting (IDW and (c Spline. Next, accuracy assessment is done based on field survey tachymetry data. The finding reveals that the overall Root Mean Square Error or RMSE for Kriging provided the lowest value of 0.727 m for both 0.5 m and 1 m spatial resolutions of oil palm area, followed by Spline with values of 0.734 m for 0.5 m spatial resolution and 0.747 m for spatial resolution of 1 m. Concurrently, IDW provided the highest RMSE value of 0.784 m for both spatial resolutions of 0.5 and 1 m. For rubber area, Spline provided the lowest RMSE value of 0.746 m for 0.5 m spatial resolution and 0.760 m for 1 m spatial resolution. The highest value of RMSE for rubber area is IDW with the value of 1.061 m for both spatial resolutions. Finally, Kriging gave the RMSE value of 0.790m for both spatial resolutions.

  19. 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 

  20. Synthesis of acyl derivatives of salicin, salirepin, and arbutin.

    Science.gov (United States)

    Stepanova, Elena V; Belyanin, Maxim L; Filimonov, Victor D

    2014-03-31

    The total synthesis of two natural phenolglycosides of the family Salicaceae, namely: populoside and 2-(β-d-glucopyranosyloxy)-5-hydroxy benzyl (3-methoxy-4-hydroxy) cinnamoate and nine not found yet in plants acyl derivatives of phenoglycosides: 2-(β-d-glucopyranosyloxy)-benzylcinnamoate, 2-(β-d-glucopyranosyloxy)-benzyl (4-hydroxy) benzoate, 2-(β-d-glucopyranosyloxy)-benzyl (3-methoxy-4-hydroxy) benzoate, 2-(β-d-glucopyranosyloxy)-5-hydroxy benzyl (3,4-dihydroxy) cinnamoate, 2-(β-d-glucopyranosyloxy)-5-hydroxy benzylcinnamoate, 2-(β-d-glucopyranosyloxy)-5-hydroxy benzyl (4-hydroxy) benzoate, 2-(β-d-glucopyranosyloxy)-5-hydroxy benzyl (3-methoxy-4-hydroxy) benzoate, 2-(β-d-glucopyranosyloxy)-5-benzoyloxy benzylbenzoate and 4-(β-d-glucopyranosyloxy)-phenylbenzoate, starting from readily available phenols and glucose was developed for the first time.

  1. Numerical methods for evaluating the derivatives of eigenvalues and eigenvectors

    Science.gov (United States)

    Rudisill, C. S.; Chu, Y.-Y.

    1975-01-01

    Two numerical methods are presented for computing the derivatives of eigenvalues and eigenvectors which do not require complete solution of the eigenvalue problem if only a few derivatives are sought. The 'iterative' method may be used to find the first derivative of one or all of the eigenvectors together with the second derivative of their eigenvalues in a self-adjoint system. If the left- and right-hand eigenvectors are known, the first derivative of the eigenvector corresponding to the largest eigenvalue and the second derivative of the largest eigenvalue may be obtained for a nonself-adjoint system. The 'algebraic' method may be used to find all orders of the derivatives, provided they exist, without requiring the left-hand eigenvectors.

  2. Quantum chemical studies on molecular structure, spectroscopic (IR, Raman, UV-Vis), NBO and HOMO-LUMO analysis of 1-benzyl-3-(2-furoyl) thiourea.

    Science.gov (United States)

    Gil, Diego M; Defonsi Lestard, M E; Estévez-Hernández, O; Duque, J; Reguera, E

    2015-06-15

    Vibrational and electronic spectra for 1-benzyl-3-(2-furoyl) thiourea were calculated by using density functional method (B3LYP) with different basis sets. The complete assignment of all vibrational modes was performed on basis of the calculated frequencies and comparing with the reported IR and Raman spectra for that thiourea derivative. UV-visible absorption spectra of the compound dissolved in methanol were recorded and analyzed using time dependent density functional theory (TD-DFT). The calculated values for the geometrical parameters of the title compound are consistent with the ones reported from XRD studies. The stability of the molecule, related to hyper-conjugative interactions, and electron delocalization were evaluated using natural bond orbital (NBO) analysis. Intra-molecular interactions were studied by AIM approach. The HOMO and LUMO analysis are used to determine the charge transfer within the molecule. Molecular electrostatic potential map was performed by the DFT method.

  3. Preparation of Novel meta- and para-Substituted N-Benzyl Protected Quinuclidine Esters and Their Resolution with Butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Srđanka Tomić

    2012-01-01

    Full Text Available Since the optically active quinuclidin-3-ol is an important intermediate in the preparation of physiologically or pharmacologically active compounds, a new biocatalytic method for the production of chiral quinuclidin-3-ols was examined. Butyrylcholinesterase (BChE; EC 3.1.1.8 was chosen as a biocatalyst in a preparative kinetic resolution of enantiomers. A series of racemic, (R- and (S-esters of quinuclidin-3-ol and acetic, benzoic, phthalic and isonicotinic acids were synthesized, as well as their racemic quaternary N-benzyl, meta- and para-N-bromo and N-methylbenzyl derivatives. After the resolution, all N-benzyl protected groups were successfully removed by catalytic transfer hydrogenation with ammonium formate (10% Pd-C. Hydrolyses studies with BChE confirmed that (R-enantiomers of the prepared esters are much better substrates for the enzyme than (S-enantiomers. Introduction of bromine atom or methyl group in the meta or para position of the benzyl moiety resulted in a considerable improvement of the stereoselectivity compared to the non-substituted compounds. Optically pure quinuclidin-3-ols were prepared in high yields and enantiopurity by the usage of various N-benzyl protected groups and BChE as a biocatalyst.

  4. Design, synthesis and insecticidal evaluation of aryloxy dihalopropene derivatives.

    Science.gov (United States)

    Yang, Ji-Chun; Li, Miao; Wu, Qiao; Liu, Chang-Ling; Chang, Xiu-Hui

    2016-02-01

    Plutella xylostella (P. xylostella) is a highly migratory, cosmopolitan species and one of the most important pest of cruciferous crops worldwide. Pyridalyl as a novel class of insecticides has good efficacy against P. xylostella. On the basis of the commercial insecticide pyridalyl, a series of new aryloxy dihalopropene derivatives were designed and synthesized by using Intermediate Derivatization Methods. Their chemical structures were confirmed by (1)H NMR, high-resolution mass spectrum (HRMS), and single-crystal X-ray diffraction analysis. The insecticidal activities of the new compounds against P. xylostella were evaluated. The results of bioassays indicated that most of the compounds showed moderate to high activities at the tested concentration, especially compounds 10e and 10g displayed more than 75% insecticidal activity against P. xylostella at 6.25mg/L, while pyridalyl showed 50% insecticidal activity at the same concentration. The field trials result of the insecticidal activities showed that compound 10e as a 10% emulsifiable concentrate (EC) was effective in the control of P. xylostella at 75-150g a.i./ha, and the mortality of P. xylostella for treatment with compound 10e at 75g a.i./ha was equivalent to pyridalyl at 105g a.i./ha.

  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. Embryolethality of butyl benzyl phthalate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Ema, N.; Itami, T.; Kawasaki, H. (National Inst. Hyg. Science, Osaka (Japan))

    1991-03-15

    The developmental toxicity of butyl benzyl phthalate (BBP) was studied in Wistar rats. Pregnant rats were given BBP at a dosage of 0, 0.25, 0.5, 1.0 or 2.0% in the diet from day 0 to day 20 of pregnancy. Morphological examinations of the fetuses revealed no evidence of teratogenesis. In the 2.0% group, all dams exhibited complete resorption of all the implanted embryos, and their food consumption, body weight gain and adjusted weight gain during pregnancy were markedly lowered. To determine whether the embryolethality was the result of reduced food consumption during pregnancy, a pair-feeding study was performed in which the pregnant rats received the same amount of diet consumed by the 2.0% BBP-treated pregnant rats. The pair-fed and 2.0 % BBP-treated pregnant rats showed significant and comparable reductions in the adjusted weight gain. The number of live fetuses was lowered in the pair-fed group. However, the complete resorption of all the implanted embryos was not found in any of the pair-fed pregnant rats. The data suggest that the embryolethality observed in the 2.0 % BBP-treated pregnant rats is attributable to the effects o dietary BBP.

  7. N-Benzyl-2,5-bis(2-thienyl)pyrrole.

    Science.gov (United States)

    Palenzuela Conde, Jesús; Elsegood, Mark R J; Ryder, Karl S

    2004-03-01

    The solid-state structure of the title compound, C19H15NS2, is unusual among substituted thiophene/pyrrole derivatives in that the molecular packing is dominated by pi-pi interactions between the benzyl substituents. This may be due to the large torsion angles observed between adjacent heterocycles. Torsion angles between adjacent rings in polypyrrole and polythiophene conducting polymers are related to conjugation length and the conductivity properties of the polymer materials. The title compound crystallizes in space group P21/c with two molecules in the asymmetric unit, both of which exhibit disorder in one of their thiophene rings.

  8. Antimicrobial Evaluation and Synthesis of Some Phenylpyrazolo benzothiazolo quinoxaline Derivatives

    OpenAIRE

    2009-01-01

    2,3-Diphenyl quinoxaline (SI) was fused with 2-amino benzothiazoles (SII) by a methylene bridge, which was then allowed for acetylation. The acetylated product (SIV) was made to react with different aromatic aldehydes to give chalcones (SV1-SV5). Chalcones refluxed with substituted acid hydrazides to afford different phenyl pyrazolo benzothiazolo quinoxaline derivatives (SVI1-SVI15). The structure of chalcones and phenyl pyrazolo benzothiazolo quinoxaline derivatives were confirmed by M.P, TL...

  9. Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl-d-Secoestrone Alcohols: The First Potent 13α-d-Secoestrone Derivative

    Directory of Open Access Journals (Sweden)

    Johanna Szabó

    2016-05-01

    Full Text Available The syntheses of C-13 epimeric 3-[(1-benzyl-1,2,3-triazol-4-ylmethoxy]-d-secoestrones are reported. Triazoles were prepared from 3-(prop-2-inyloxy-d-secoalcohols and p-substituted benzyl azides via Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC. The antiproliferative activities of the products and their precursors were determined in vitro against a panel of human adherent cervical (HeLa, SiHa and C33A, breast (MCF-7, MDA-MB-231, MDA-MB-361 and T47D and ovarian (A2780 cell lines by means of MTT assays. The orientation of the angular methyl group and the substitution pattern of the benzyl group of the azide greatly influenced the cell growth-inhibitory potential of the compounds. The 13β derivatives generally proved to be more potent than their 13α counterparts. Introduction of a benzyltriazolylmethyl group onto the 3-OH position seemed to be advantageous. One 13α compound containing an unsubstituted benzyltriazolyl function displayed outstanding antiproliferative activities against three cell lines.

  10. A Facile Synthesis of Substituted Benzyl Selenocyanatesâ€

    Directory of Open Access Journals (Sweden)

    Joanne Kivella Tillotson

    2004-07-01

    Full Text Available Benzyl selenocyanates can be made from the corresponding benzylic bromides or chlorides in 30-60 minutes using acetonitrile as a solvent. The products may be obtained pure in satisfactory yields without recourse to chromatography.

  11. 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.

  12. Synthesis and Biological Evaluation of Some New Coumarin Derivatives

    Directory of Open Access Journals (Sweden)

    M. Y. El-Kady

    2003-02-01

    Full Text Available Pyrimidino[5`,4`-6,5]-,pyridino[3`,2`-6,5]- and pyrrolo[3`,2`-5,6]4H-pyrano-[3,2-c][1]benzopyran-6-one derivatives (5-7 and 10 could be obtained via reaction of 2-amino-4-(p-bromophenyl-3-cyano(carboethoxy-4H,5H-pyrano[3,2-c][1]benzopyran-5-ones (3a,b with a variety of reagents. Alkylation of (3b with either 2-furoyl chloride or chloroacetyl chloride gave the 2-N-substituted derivatives (9a,b. Benzofurano[3,2-b]4H-pyran derivative (12 was also prepared. The antimicrobial activity of the prepared compounds was tested.

  13. Synthesis and antiretroviral evaluation of derivatives of zidovudine

    Energy Technology Data Exchange (ETDEWEB)

    Raviolo, Monica A.; Brin, Margarita C. [Universidad Nacional de Cordoba, Cordoba (Argentina). Facultad de Ciencias Quimicas. Dept. de Farmacia; Trinchero-Hernandez, Juan S.; Turk, Gabriela [Universidad de Buenos Aires, Buenos Aires (Argentina). Facultad de Medicina. Centro Nacional de Referencia para el SIDA

    2009-07-01

    A series of zidovudine (AZT, 1) derivatives have been synthesized and their anti-HIV activity and cytotoxicity have been determined. The 5'-OH function of AZT was derivatized using N, N'-carbonyldiimidazole and different amine compounds leading to their 5'-O-carbamates. In addition, two known AZT derivatives 5'-O-tosylate and a tricyclic one (AZT-Cycl) were also obtained by a simpler procedure than those previously reported. Although these AZT derivatives were less toxic than AZT, their reduced cytotoxicity was concomitant with an inability to inhibit HIV-1 replication, except in the case of AZT-Cycl, which showed an IC{sub 50} = 1 {mu}mol L{sup -1} without cytotoxicity with values of CCID{sub 50} ({mu}mol L{sup -1}) > 1000. (author)

  14. Antimicrobial Evaluation and Synthesis of Some Phenylpyrazolo benzothiazolo quinoxaline Derivatives

    Directory of Open Access Journals (Sweden)

    CH. Sridevi

    2009-01-01

    Full Text Available 2,3-Diphenyl quinoxaline (SI was fused with 2-amino benzothiazoles (SII by a methylene bridge, which was then allowed for acetylation. The acetylated product (SIV was made to react with different aromatic aldehydes to give chalcones (SV1-SV5. Chalcones refluxed with substituted acid hydrazides to afford different phenyl pyrazolo benzothiazolo quinoxaline derivatives (SVI1-SVI15. The structure of chalcones and phenyl pyrazolo benzothiazolo quinoxaline derivatives were confirmed by M.P, TLC and spectral data. All the synthesized compounds were screened for their antimicrobial activities.

  15. Design, synthesis and antidiabetic evaluation of oxazolone derivatives

    Indian Academy of Sciences (India)

    G Mariappan; B P Saha; Sriparna Datta; Deepak Kumar; P K Haldar

    2011-05-01

    A series of ten novel (2a-j) 4-arylidine 2-[4-methoxy phenyl] oxazol-5-one derivatives were synthesized and assayed in vivo to investigate their antidiabetic activities by streptozotocin-induced model in rat. These derivatives showed considerable biological efficacy when compared to rosiglitazone, a potent and wellknown antidiabetic agent as a reference drug. All the compounds were effective, amongst them 2d shows more prominent activity at 50 mg/k.g.p.o. The experimental results are statistically significant at P < 0.01 level.

  16. Benzyl-chloridobis(quinolin-8-olato)tin(IV).

    Science.gov (United States)

    Wang, Qibao

    2009-07-11

    In the title compound, [Sn(C(7)H(7))(C(9)H(6)NO)(2)Cl], the Sn(IV) ion is in a distorted octa-hedral coordination environment formed by the O and N atoms of two bis-chelating quinolin-8-olate ligands, a Cl atom and a C atom from a benzyl ligand. The axial sites are occupied by an N atom of a quinolinate ligand and the C atom of the benzyl ligand. The axial Sn-N bond is slightly shorter than the equatorial Sn-N bond.

  17. Benzyl­chloridobis(quinolin-8-olato)tin(IV)

    OpenAIRE

    Wang, Qibao

    2009-01-01

    In the title compound, [Sn(C7H7)(C9H6NO)2Cl], the SnIV ion is in a distorted octa­hedral coordination environment formed by the O and N atoms of two bis-chelating quinolin-8-olate ligands, a Cl atom and a C atom from a benzyl ligand. The axial sites are occupied by an N atom of a quinolinate ligand and the C atom of the benzyl ligand. The axial Sn—N bond is slightly shorter than the equatorial Sn—N bond.

  18. Growth and characterization of organic single crystal benzyl carbamate

    Science.gov (United States)

    Bala Solanki, S. Siva; Perumal, Rajesh Narayana; Suthan, T.; Bhagavannarayana, G.

    2015-10-01

    Benzyl carbamate single crystal is grown by a solution and vertical Bridgman technique for the first time. The cell parameters and morphologies are assessed from single crystal X-ray diffraction analysis. High resolution X-ray diffraction analysis indicates the crystalline perfection of the grown benzyl carbamate crystal. Fourier Transforms Infrared spectroscopy study has been applied to arrive at the different functional groups. Thermo gravimetric analysis and differential scanning calorimetry are used to study its thermal behavior. The microhardness test is carried out and the load dependent hardness is measured.

  19. A convenient procedure for the synthesis of allyl and benzyl ethers from alcohols and phenols

    Indian Academy of Sciences (India)

    H Surya Prakash Rao; S P Senthilkumar

    2001-06-01

    Allyl and benzyl ethers of alcohols can be prepared conveniently and in high yield with allyl and benzyl bromide in the presence of solid potassium hydroxide without use of any solvent. Phenols can be converted to allyl ethers but are inert to benzylation under above conditions.

  20. Approach to a Facile and Selective Benzyl-Protection of Carbohydrates Based on Silyl Migration

    Institute of Scientific and Technical Information of China (English)

    WANG,Wei; LI,Xiao-Liu; ZHANG,Ping-Zhu; CHEN,Hua

    2008-01-01

    A convenient and selective benzyl protection of carbohydrates has been investigated on the basis of the silyl migration under the conventional benzylation conditions, developing a facile and short synthesis of methyl 2,3,6-tri-O-benzyl-a-D-glucopyranoside.

  1. Ultrasonic Investigations of Molecular Interaction in Binary Mixtures of Benzyl Benzoate with Acetonitrile and Benzonitrile

    Directory of Open Access Journals (Sweden)

    N. Jaya Madhuri

    2011-01-01

    Full Text Available Ultrasonic velocity, density and viscosity have been measured in the binary mixtures of benzyl benzoate with acetonitrile, benzonitrile at three temperatures 30, 40 and 50 °C. From the experimental data, thermodynamic parameters like adiabatic compressibility, internal pressure, enthalpy, activation energy etc., were computed and the molecular interactions were predicted based on the variation of excess parameters in the mixture. Also theoretical evaluation of velocities was made employing the standard theories. CFT and NOMOTO were found to have an edge. All the three mixtures have shown out strong intermolecular interactions between the unlike molecules and endothermic type of chemical reaction.

  2. 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.

  3. 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.

  4. Synthesis and biological evaluation of some New pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Firyal Weli Askar

    2017-06-01

    Full Text Available New pyrimidine derivatives comprising azo, schiff's bases, chalcones, and chromene ring moieties were prepared.The newly synthesized compounds have been established on the basis of their m.p., TLC, FT-IR, UV-Vis ,¹H-NMR data and element analysis. These compounds were screened for their antimicrobial and in vitro antioxidant properties. The results of this investigation revealed that these compounds are potent antimicrobial and antioxidant agent.

  5. Synthesis and Biological Evaluation of Thiophene Derivatives as Acetylcholinesterase Inhibitors

    Directory of Open Access Journals (Sweden)

    Mai A. Galal

    2012-06-01

    Full Text Available A series of new thiophene derivatives has been synthesized using the Gewald protocol. The acetylcholinesterase inhibition activity was assayed according to Ellman’s method using donepezil as reference. Some of the compounds were found to be more potent inhibitors than the reference. 2-(2-(4-(4-Methoxyphenylpiperazin-1-ylacetamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (IIId showed 60% inhibition, compared to only 40% inhibition by donepezil.

  6. Pd@Cu(II)-MOF-Catalyzed Aerobic Oxidation of Benzylic Alcohols in Air with High Conversion and Selectivity.

    Science.gov (United States)

    Chen, Gong-Jun; Wang, Jing-Si; Jin, Fa-Zheng; Liu, Ming-Yang; Zhao, Chao-Wei; Li, Yan-An; Dong, Yu-Bin

    2016-03-21

    A new 3D porous Cu(II)-MOF (1) was synthesized based on a ditopic pyridyl substituted diketonate ligand and Cu(OAc)2 in solution, and it features a 3D NbO motif which is determined by the X-ray crystallography. Furthermore, the Pd NPs-loaded hybrid material Pd@Cu(II)-MOF (2) was prepared based on 1 via solution impregnation, and its structure was confirmed by HRTEM, SEM, XRPD, gas adsorption-desorption, and ICP measurement. 2 exhibits excellent catalytic activity (conversion, 93% to >99%) and selectivity (>99% to benzaldehydes) for various benzyl alcohol substrates (benzyl alcohol and its derivatives with electron-withdrawing and electron-donating groups) oxidation reactions in air. In addition, 2 is a typical heterogeneous catalyst, which was confirmed by hot solution leaching experiment, and it can be recycled at least six times without significant loss of its catalytic activity and selectivity.

  7. Evaluation of photosynthetic electrons derivation by exogenous redox mediators.

    Science.gov (United States)

    Longatte, Guillaume; Fu, Han-Yi; Buriez, Olivier; Labbé, Eric; Wollman, Francis-André; Amatore, Christian; Rappaport, Fabrice; Guille-Collignon, Manon; Lemaître, Frédéric

    2015-10-01

    Oxygenic photosynthesis is the complex process that occurs in plants or algae by which the energy from the sun is converted into an electrochemical potential that drives the assimilation of carbon dioxide and the synthesis of carbohydrates. Quinones belong to a family of species commonly found in key processes of the Living, like photosynthesis or respiration, in which they act as electron transporters. This makes this class of molecules a popular candidate for biofuel cell and bioenergy applications insofar as they can be used as cargo to ship electrons to an electrode immersed in the cellular suspension. Nevertheless, such electron carriers are mostly selected empirically. This is why we report on a method involving fluorescence measurements to estimate the ability of seven different quinones to accept photosynthetic electrons downstream of photosystem II, the first protein complex in the light-dependent reactions of oxygenic photosynthesis. To this aim we use a mutant of Chlamydomonas reinhardtii, a unicellular green alga, impaired in electron downstream of photosystem II and assess the ability of quinones to restore electron flow by fluorescence. In this work, we defined and extracted a "derivation parameter" D that indicates the derivation efficiency of the exogenous quinones investigated. D then allows electing 2,6-dichlorobenzoquinone, 2,5-dichlorobenzoquinone and p-phenylbenzoquinone as good candidates. More particularly, our investigations suggested that other key parameters like the partition of quinones between different cellular compartments and their propensity to saturate these various compartments should also be taken into account in the process of selecting exogenous quinones for the purpose of deriving photoelectrons from intact algae. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Iron-catalysed Negishi coupling of benzyl halides and phosphates.

    Science.gov (United States)

    Bedford, Robin B; Huwe, Michael; Wilkinson, Mark C

    2009-02-01

    Iron-based catalysts containing either 1,2-bis(diphenylphosphino)benzene or 1,3-bis(diphenylphosphino)propane give excellent activity and good selectivity in the Negishi coupling of aryl zinc reagents with a range of benzyl halides and phosphates.

  9. Biocatalytic oxidation of benzyl alcohol to benzaldehyde via hydrogen transfer

    NARCIS (Netherlands)

    Orbegozo, Thomas; Lavandera, Iván; Fabian, Walter M.F.; Mautner, Barbara; Vries, Johannes G. de; Kroutil, Wolfgang

    2009-01-01

    Various types of biocatalysts like oxidases, alcohol dehydrogenases, and microbial cells were tested for the oxidation of benzyl alcohol. Oxidases in combination with molecular oxygen led to low conversion. Alcohol dehydrogenases and microbial cells were tested in a hydrogen transfer reaction employ

  10. 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.

  11. Synthesis and biological evaluation of some novel 4H-benzopyran-4-one derivatives as nonsteroidal antiestrogens.

    Science.gov (United States)

    Ismail, K A; Abd El Aziem, T

    2001-03-01

    The preparation and characterization of some novel 2- and 3-substituted-7-methoxy-4H-1-benzopyran-4-one are presented. The synthesized compounds were evaluated for their uterotrophic, antiuterotrophic and antiimplantation activities in mature female albino rats. 3-Benzyl-7-methoxy-4H-1-benzopyran-4-one (14) showed the highest uterotrophic activity (87%) based on dry uterine weight gain. The antifertility activity, as assessed by the post-coital antiimplantation activity test, was of weak potency for most compounds (14-29%). Among the products, the 2-(4'-methoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one (19) exhibited the highest antiestrogenic activity of 65%. It also elicited 31% of the uterotrophic activity of estradiol.

  12. Facile synthesis and stereochemical investigation of Mannich base derivatives: evaluation of antioxidant property and antituberculostic potency.

    Science.gov (United States)

    Parthiban, Paramasivam; Subalakshmi, Viswalingam; Balasubramanian, Krishnamurthy; Islam, Md Nurul; Choi, Jae Sue; Jeong, Yeon Tae

    2011-04-15

    A mini-library of diversely substituted 2,4-diaryl-3-azabicyco[3.3.1]nonan-9-one O-methyloximes and their N-methyl analogs were synthesized by a non-laborious, modified and an optimized Mannich condensation in good yields. Both the ring N-methylation and oxime O-methylation were employed by various methods; of them, the usage of (t)BuOK was found to be the superior in terms of good yield in short time. Stereochemistry of all the synthesized compounds was unambiguously established by their NMR spectral ((1)H, (13)C, (1)H-(1)H COSY, (1)H-(13)C one and multiple bond COSY and NOESY) as well as single-crystal XRD studies. Irrespective of the nature and position of the substituents, all the synthesized oxime ethers of the bicyclic Mannich bases as well as their N-methyl analogs adopted the twin-chair conformation with equatorial orientations of all the substituents. All the synthesized oxime ethers were evaluated for their antioxidant property by DPPH radical scavenging method. According to the structure-activity correlations, compound 4y was found to be a lead molecule with the IC(50) of 0.187 mg/mL. Thus, the present study exploits the scope of finding more active analogs by further optimization with the incorporation of more electron enriched alkoxy/amino and/or phenolic groups on the heterocycle as well as oxime ether pharmacophore. Most of the synthesized molecules were screened for their antituberculostic potency against Mycobacterium tuberculosis H(37)Rv by zone of inhibition method. Of them, 4w/5d and 4x showed very promising inhibition zones of 21 and 23 mm, respectively, which leads to the optimization of 4x by introducing various substituents on the O-benzyl moiety to enhance the antituberculostic potency.

  13. Evaluating large scale orthophotos derived from high resolution satellite imagery

    Science.gov (United States)

    Ioannou, Maria Teresa; Georgopoulos, Andreas

    2013-08-01

    For the purposes of a research project, for the compilation of the archaeological and environmental digital map of the island of Antiparos, the production of updated large scale orthophotos was required. Hence suitable stereoscopic high resolution satellite imagery was acquired. Two Geoeye-1 stereopairs were enough to cover this small island of the Cyclades complex in the central Aegean. For the orientation of the two stereopairs numerous ground control points were determined using GPS observations. Some of them would also serve as check points. The images were processed using commercial stereophotogrammetric software suitable to process satellite stereoscopic imagery. The results of the orientations are evaluated and the digital terrain model was produced using automated and manual procedures. The DTM was checked both internally and externally with comparison to other available DTMs. In this paper the procedures for producing the desired orthophotography are critically presented and the final result is compared and evaluated for its accuracy, completeness and efficiency. The final product is also compared against the orthophotography produced by Ktimatologio S.A. using aerial images in 2007. The orthophotography produced has been evaluated metrically using the available check points, while qualitative evaluation has also been performed. The results are presented and a critical approach for the usability of satellite imagery for the production of large scale orthophotos is attempted.

  14. SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF SOME NOVEL THIAZOLIDINONES DERIVATIVES

    Directory of Open Access Journals (Sweden)

    S. Chandramohan et al.

    2012-05-01

    Full Text Available The main objective of the medicinal chemistry is to synthesize the compounds that show promising activity and therapeutic agents with lower toxicity. Thiazolidinone are very useful compound with well known biological activities. Notable among these are antibacterial, antiviral, analgesic, anti-inflammatory, antitubercular and anticonvulsant. In the current research work, three novel substituted thiazolidin-4-one derivatives were prepared from the corresponding Schiff bases and 2-mercapto acetic acid in benzene using Stark and Dean Apparatus. The identification and characterization of synthesized compounds were carried out by Elemental analysis, FT-IR and NMR data to ascertain that all synthesized compounds were of different chemical nature than the respective parent compound. The synthesized compounds showed good antibacterial activity against Escherichia Coli, Staphylococcus, Pseudomonas aeruginosa and Salmonella typhi.

  15. 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.

  16. Synthesis and preliminary pharmacological evaluation of some cytisine derivatives.

    Science.gov (United States)

    Canu Boido, C; Sparatore, F

    1999-07-30

    Thirty-one N-derivatives of cytisine were prepared in order to modify its pharmacological profile and to obtain compounds of potential therapeutic interest either at a peripheral or central level, particularly as nicotinic ligands with improved ability to cross the blood-brain barrier. Actually, with the introduction of different kinds of substituent on the basic nitrogen of cytisine a variety of activities were observed, both in vivo (analgesic, dopamine antagonism, antihypertensive, inhibition of stress-induced ulcers, antiinflammatory, protection from PAF-induced mortality, hypoglycemic) and in vitro (positive cardio-inotropic, beta-adrenergic antagonism, alpha 1- and alpha 2-antagonism, inhibition of PAF-induced platelet aggregation). Six randomly selected compounds were tested for the ability to recognize a central nicotinic receptor and four of them exhibited Ki values in the range 30-163 nM.

  17. Synthesis, Evaluation and Docking studies of Cholecalciferol Derivative

    Directory of Open Access Journals (Sweden)

    Sultanat

    2014-09-01

    Full Text Available Improved synthesis of 3b-acetoxy-9, 10-seco-19, 8(8-spiro-5(10, 6-cholestadiene has been reported after reacting cholecalciferol acetate with dimethylbutadiene by incorporating BF3·OEt2, SnCl4, ZnBr2, p-TsOH in toluene under Diels-Alder condition to get better yields. Agarose gel electrophoresis showed the potential in vitro DNA damaging nature while as the comet assay depicted the genotoxic nature by mobilizing the tail of the comet in lymphocytes. The molecular docking depicted the intercalation of steroid derivative with minor groove of the DNA molecule and in this configuration the phosphodiester bond of DNA stabilizes the acetoxy group. The bioactivity score and PASS software analysis confirmed the potential physicochemical features of the compound to act as active drug.

  18. 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.

  19. Immunogenicity and functional evaluation of iPSC-derived organs for transplantation.

    Science.gov (United States)

    Wang, Libin; Cao, Jiani; Wang, Yukai; Lan, Tianshu; Liu, Lei; Wang, Weixu; Jin, Ning; Gong, Jiaqi; Zhang, Chao; Teng, Fei; Yan, Guoliang; Li, Chun; Li, Jiali; Wan, Haifeng; Hu, Baoyang; Li, Wei; Zhao, Xiaoyang; Qi, Zhongquan; Zhao, Tongbiao; Zhou, Qi

    2015-01-01

    Whether physiologically induced pluripotent stem cell (iPSC)-derived organs are immunogenic and can be used for transplantation is unclear. Here, we generated iPSC-derived skin, islet, and heart representing three germ layers of the body through 4n complementation and evaluated their immunogenicity and therapeutic efficacy. Upon transplantation into recipient mice, iPSC-derived skin successfully survived and repaired local tissue wounds. In diabetic mouse models, explanted iPSC-derived islets effectively produced insulin and lowered blood glucose to basal levels. iPSC-derived heart grafts maintained normal beating for more than 3 months in syngeneic recipients. Importantly, no obvious immune rejection responses against iPSC-derived organs were detected long after transplantation. Our study not only demonstrates the fundamental immunogenicity and function of iPSC derivatives, but also provides preclinical evidence to support the feasibility of using iPSC-derived skin, islet, and heart for therapeutic use.

  20. Synthesis and Biological Evaluation of Hydrazone Derivatives as Antifungal Agents

    Directory of Open Access Journals (Sweden)

    Bruna B. Casanova

    2015-05-01

    Full Text Available Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a and tert-butyl-(2Z-2-(3,4,5-trihydroxybenzylidinehydrazine carboxylate (7b showed the most promising MIC values in the range of 16–32 μg/mL and 8–16 μg/mL, respectively. The compounds’ action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents.

  1. Synthesis and pharmacological evaluation of new 16-methyl pregnane derivatives.

    Science.gov (United States)

    Ramirez, Elena; Cabeza, Marisa; Heuze, Ivonne; Gutiérrez, Edgar; Bratoeff, Eugene; Membrillo, Marisol; Lira, Alfonso

    2002-01-01

    The pharmacological activity of several new pregnane derivatives 15-19 were determined on gonadectomized male hamster flank organs, seminal vesicles and in vitro conversion of testosterone (T) to dihydrotestosterone (DHT) as 5alpha-reductase inhibitors. Steroids 15-19 decreased the diameter of the pigmented spot in the flank organs as compared to the T treated animals; in this model, steroids 16 and 19 showed a higher activity than the commercially available finasteride 3. Injection of T increased the weight of the seminal vesicles. Compounds 15-19 when injected together with T decreased the weight of the seminal vesicles thus showing an antiandrogenic effect. The trienone 19 exhibited a considerably higher activity than finasteride. Steroids 15-19 inhibited the in vitro metabolism of [3H]T to [3H]DHT in seminal vesicles homogenates of gonadectomized male hamsters. Compounds 18 and 19 showed a much higher antiandrogenic effect than finasteride. This enhancement of the biological activity could probably be attributed to the coplanarity of the steroidal skeleton as previously observed by our group. The high antiandrogenic activity of the epoxy compound 16 is probably the result of the ring opening of the oxiran ring with the nucleophilic part of the enzyme 5alpha-reductase thus leading to a stable adduct with concomitant deactivation of this enzyme.

  2. Synthesis and Biological Evaluation of Aminonaphthols Incorporated Indole Derivatives

    Directory of Open Access Journals (Sweden)

    Saundane Anand Raghunath

    2014-01-01

    Full Text Available An efficient one pot condensation of naphthols (1, 2,5-disubstituted indole-3-carboxaldehydes (2, and secondary amines (3 has been achieved using dichloromethane as a solvent, stirring at room temperature. Some of the new [(disubstituted amino(5-substituted 2-phenyl-1H-indol-3-ylmethyl]naphthalene-ols (4 derivatives were prepared in good yields. The significant features of this method are simple work-up procedure, inexpensive nontoxic solvent, shorter reaction times, and excellent product yields. The structures of newly synthesized compounds (4a–r are confirmed by their elemental analysis, FTIR, 1H and 13C NMR, and mass spectral data. These compounds were screened for their in vitro antioxidant, antimicrobial, antitubercular, and anticancer activities. Among the synthesized compounds (4a–r, the compound 4e exhibited highest activity for radical scavenging and ferric ions reducing antioxidant power activities; compounds 4b, 4h, and 4k showed good metal chelating activity. Compounds 4n and 4q showed excellent antimicrobial activities with MIC value 08 µg/mL against tested strains. Compounds 4h, 4k, 4n, and 4q exhibited promising antitubercular activity with MIC value 12.5 µg/mL. Compounds 4k and 4q exhibited 100% cell lysis at concentration 10 µg/mL against MDA-MB-231 (human adenocarcinoma mammary gland cell lines.

  3. Synthesis and biological evaluation of chalcone derivatives (mini review).

    Science.gov (United States)

    Bukhari, Syed Nasir Abbas; Jasamai, Malina; Jantan, Ibrahim

    2012-11-01

    Chalcones are the principal precursors for the biosynthesis of flavonoids and isoflavonoids. A three carbon α, β-unsaturated carbonyl system constitutes chalcones. Chalcones are the condensation products of aromatic aldehyde with acetophenones in attendance of catalyst. They go through an assortment of chemical reactions and are found advantageous in synthesis of pyrazoline, isoxazole and a variety of heterocyclic compounds. In synthesizing a range of therapeutic compounds, chalcones impart key role. They have showed worth mentioning therapeutic efficacy for the treatment of various diseases. Chalcone based derivatives have gained heed since they own simple structures, and diverse pharmacological actions. A lot of methods and schemes have been reported for the synthesis of these compounds. Amongst all, Aldol condensation and Claisen-Schmidt condensation still grasp high up position. Other distinguished techniques include Suzuki reaction, Witting reaction, Friedel-Crafts acylation with cinnamoyl chloride, Photo-Fries rearrangement of phenyl cinnamates etc. These inventive techniques utilize various catalysts and reagents including SOCl(2) natural phosphate, lithium nitrate, amino grafted zeolites, zinc oxide, water, Na(2)CO(3), PEG400, silicasulfuric acid, ZrCl(4) and ionic liquid etc. The development of better techniques for the synthesis of α, β- unsaturated carbonyl compounds is still in high demand. In brief, we have explained the methods and catalysts used in the synthesis of chalcones along with their biological activities in a review form to provide information for the development of new-fangled processes targeting better yield, less reaction time and least side effects with utmost pharmacological properties.

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

    Science.gov (United States)

    Zou, Shiying; He, Xiaoyun; 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.

  5. 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.

  6. Design synthesis and biological evaluation of 3-substituted triazole derivatives

    Institute of Scientific and Technical Information of China (English)

    Bao Gang Wang; Shi Chong Yu; Xiao Yun Chai; Yong Zheng Yan; Hong Gang Hu; Qiu Ye Wu

    2011-01-01

    Based on the active site of lanosterol 14α-demethylase of azole antifungal agents, sixteen l-(lH-l,2,4-triazole-l-yl)- 2-(2,4-difluorophenyl)-3-(N-n-butyl-N-l-substitutedbenzyl-4-methylene-lH-l,2,3-triazole)-2-propanols have been designed, synthesized and evaluated as antifungal agents. Results of preliminary antifungal tests against eight human pathogenic fungi in vitro showed that some of the compounds exhibited excellent activities with broad spectrum.

  7. Fe3+-Exchanged Titanate Nanotubes: A New Kind of Highly Active Heterogeneous Catalyst for Friedel-Crafts Type Benzylation

    Directory of Open Access Journals (Sweden)

    Yunchen Du

    2015-01-01

    Full Text Available Heterogeneous catalysis for Friedel-Crafts type benzylation has received much attention in recent years due to its characteristic of environmental benefits. In this paper, titanate nanotubes (TNTs were employed as heterogeneous catalyst support, and a new kind of Fe3+-exchanged titanate nanotubes (Fe-TNTs catalyst with highly dispersed ferric sites was constructed by an ion exchange technique. The obtained catalyst was systematically characterized by XRD, TEM, N2 adsorption, XPS, and UV-vis spectra. As expected, Fe-TNTs showed excellent catalytic activities in the benzylation of benzene and benzene derivatives. The recycling tests for Fe-TNTs were also carried out, where the reason for the gradually decreased activity was carefully investigated. Superior to some reported catalysts, the catalytic ability of used Fe-TNTs could be easily recovered by ion exchange again, indicating that Fe-TNTs herein were a highly active and durable heterogeneous catalyst for Friedel-Crafts type benzylation. These results might be helpful for the design and preparation of novel heterogeneous catalysts by combining the structural advantages of titanate nanotubes and active metal ions.

  8. Synthesis and antioxidant evaluation of some new pyrazolopyridine derivatives.

    Science.gov (United States)

    Gouda, Moustafa A

    2012-02-01

    4,6-Dimethyl-1H-pyrazolo[3,4-b]pyridine-3-amine (1) was used as a key intermediate for the synthesis of imidazolopyrazole derivatives 7-11 upon interaction with 3-(2-bromoacetyl)-2H-chromen-2-one (2), 2-(benzothiazol-2-yl)-4-chloro-3-oxobutanenitrile (3), 2,3-dibromonaphthalene-1,4-dione (4), naphtha[2,3-b]oxirene-2,7-dione (5), 2,5-dichloro-3,6-dihydroxyhexa-2,5-diene-1,4-dione (6), respectively. Acetylation of 11 afforded the bis-acetyl 12. Also, the imidazolopyrimidine 15 was prepared via treatment of 1 with sodium 3,4-dioxo-3,4-dihydronaphthalene-1-sulfonate (13) in DMF followed by cyclization of the bis-pyrazolopyrimidine 14 with glacial acetic acid. On the other hand, compound 1 was reacted with (E)-1-(4-methoxyphenyl)-5-(piperidin-1-yl)pent-1-en-3-one hydrochloride (16), 2-hydroxy-3-((piperidin-1-yl)-methyl)-naphthalene-1,4-dione (17), 2-styryl-2H-indene-1,3-dione (18), enaminone 22, chloroquinoline-3-carbaldehyde 27a, chloroquinoline-(6-methyl)-3-carbaldehyde 27b and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (28) to afford pyrazolo[3,4-a]pyrimidines 19-21, 23, 29a, 29b and 30, respectively. Also, the pyrazolopyrimidinone 33 was obtained via treatment of 1 with 1-cyanoacetyl-3,5-dimethylpyrazole (31) followed by cyclization of the formed intermediate 32 with glacial acetic acid. Finally, treatment of 1 with o-terephthalaldehyde in glacial acetic acid afforded diazepine 34. The newly synthesized compounds were screened for their antioxidant properties in which some of them exhibited promising activities. Compounds 1, 14, 15, 23, 26, 29a, 30 and 32 have the ability to protect DNA from the damage induced by bleomycin.

  9. Synthesis and antimicrobial activities of hexahydroimidazo[1,5-a]pyridinium bromides with varying benzyl substituents.

    Science.gov (United States)

    Türkmen, Hayati; Ceyhan, Nur; Ulkü Karabay Yavaşoğlu, N; Ozdemir, Güven; Cetinkaya, Bekir

    2011-07-01

    Variously substituted benzyl bromides were employed to quaternize hexahydrobenzylimidazo[1,5-a]pyridine (A) and the resulting bromides (1-11) were evaluated for their in vitro antimicrobial activity against 10 pathogenic microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Micrococcus luteus, Proteus vulgaris, Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia, Candida albicans and Candida krusei. Antimicrobial activities were surprisingly high (MIC: 0.78-400 μg/mL) and the sensitivity of the salts tested has been found to depend strongly both on the benzyl substituents and the microorganisms used. However, the correlation observed between antimicrobial activity and calculated partition coefficient (ClogP) was poor. Acute toxicity assessment of these salts showed LD(50) of 757-2000 mg/kg, after oral administration in mice in 24h. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  10. Deriving equity from expectations: A cross-cultural evaluation.

    Science.gov (United States)

    Melamed, David

    2012-01-01

    This paper develops and evaluates a new model for predicting just rewards. The model produces point predictions for individual just rewards based on status characteristics and the expected value of a valued good. The equity model borrows from Berger and colleagues' (1998) reward expectations theory the ability to define different reward expectations. Drawing from Melamed and Walker's (2010) recent generalization of the mathematics of reward expectations theory, I illustrate how the model generates a continuous distribution of just rewards. The general model is applied to data from thirteen countries using the International Social Justice Project. The results illustrate the predictive power of the model using data from over 10,000 respondents. Implications and future directions are discussed.

  11. 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.

  12. Synthesis and Antimicrobial Evaluation of Some Pyrazole Derivatives

    Directory of Open Access Journals (Sweden)

    Nagwa Mohamed Mahrous Hamada

    2012-04-01

    Full Text Available Reaction of a series of (E-3-phenyl-4-(p-substituted phenyl-3-buten-2-ones with p-sulfamylphenyl hydrazine in glacial acetic acid gave the corresponding hydrazones, subsequent treatment of which with 30% HCl afforded pyrazole-1-sulphonamides. On the other hand, refluxing of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide in ethanol containing a few drops of acetic acid gave pyrazoline-1-thiocarboxamides and isonicotinoyl pyrazolines, respectively. The structures of the synthesized compounds were determined on the basis of their elemental analyses and spectroscopic data. The antimicrobial activity of the newly isolated heterocyclic compounds was evaluated against Gram-positive, Gram-negative bacteria and fungi. Most of the compounds showed a moderate degree of potent antimicrobial activity.

  13. Synthesis and Biological Evaluation of Andrographolide C-Glycoside Derivatives as a-Glycosidase Inhibitors

    Institute of Scientific and Technical Information of China (English)

    严琳; 徐海伟; 刘丰五; 赵瑾; 刘宏民

    2012-01-01

    A series of new andrographolide C-glycoside derivatives were synthesized by a facile route. The new com- pounds showed higher potency than the parent andrographolide evaluated as a-glycosidase inhibitors in the pre- liminary study.

  14. Determination of NO chemical affinities of benzyl nitrite in acetonitrile

    Institute of Scientific and Technical Information of China (English)

    Xin LI; Xiaoqing ZHU; Jinpei CHENG

    2008-01-01

    There is an increasing interest in the study of NO chemical affinities of organic nitrites, for the bio-logical and physiological effects of organic nitrites seem to be due to their ability to release NO. In this paper, NO chemical affinities of ten substituted benzyl nitrites were determined by titration calorimetry combined with a ther-modynamic cycle in acetonitrile solution. The results show that ΔHhet(O-NO)s of benzyl nitrites are substan-tially larger than the corresponding ΔHhomo(O-NO)s, suggesting that these O-nitroso compounds much more easily release NO radicals by the O-NO bond homolytic cleavage. It is believed that the structural and energetic information disclosed in this work should be useful in understanding chemical and biological functions of organic nitrites.

  15. 3-Benzyl-5-methyl-1,2-benzoxazole 2-oxide

    Directory of Open Access Journals (Sweden)

    G. Anuradha

    2012-10-01

    Full Text Available In the title compound, C15H13NO2, the isoxazole unit and the attached benzene ring are almost coplanar, making a dihedral angle of 1.42 (8°. The benzyl ring is inclined to the isoxazole ring by 74.19 (8° and is in a +sc conformation with respect to the benzisoxazole unit. In the crystal, C—H...O hydrogen bonds link the molecules, forming zigzag chains propagating along the b axis. There are also π–π interactions present involving the isoxazole and benzyl rings [centroid–centroid distance = 3.5209 (10 Å], and C—H...π interactions involving the benzene ring of the benzoisoxazole unit and the methylene bridging group.

  16. Fast Numerical Evaluation of Time-Derivative Nonadiabatic Couplings for Mixed Quantum-Classical Methods.

    Science.gov (United States)

    Ryabinkin, Ilya G; Nagesh, Jayashree; Izmaylov, Artur F

    2015-11-05

    We have developed a numerical differentiation scheme that eliminates evaluation of overlap determinants in calculating the time-derivative nonadiabatic couplings (TDNACs). Evaluation of these determinants was the bottleneck in previous implementations of mixed quantum-classical methods using numerical differentiation of electronic wave functions in the Slater determinant representation. The central idea of our approach is, first, to reduce the analytic time derivatives of Slater determinants to time derivatives of molecular orbitals and then to apply a finite-difference formula. Benchmark calculations prove the efficiency of the proposed scheme showing impressive several-order-of-magnitude speedups of the TDNAC calculation step for midsize molecules.

  17. Synthesis and Biological Evaluation of Metronidazole Derivatives as Anti-Giardia Agents

    Directory of Open Access Journals (Sweden)

    Bahador Shahriari

    2015-06-01

    Full Text Available Nitroimidazole derivatives such as Metronidazole (MTZ have been used as anti- protozoa and anti-anaerobic bacteria. In this study several derivatives of MTZ were synthesized and evaluated against Giardia lamblia cyst. MTZ were reacted with several alkyl halide to obtain o-alkyl MTZ derivatives, then products were purified and their chemical structures were confirmed by spectral analysis (1HNMR and Mass. In order to assess biological evaluation, all compounds were investigated against 25 Giardia samples isolated from Giardia-infected patients. Results showed that compound 2 had the most activity on cyst of Giardia in comparison with MTZ.

  18. Synthesis and Properties of Polyurethane Resins from Liquefied Benzylated Wood

    Institute of Scientific and Technical Information of China (English)

    Yu Ping WEI; Fa CHENG; Hou Ping LI; Jiu Gao YU

    2005-01-01

    In this paper, polyurethane resins were synthesized from liquefied benzylated wood and TDI (toluene diisocyanate)-TMP (trihydromethylene propane) prepolymer. And the relation between microphase structure and properties of PU samples were also studied. The results indicated that coatings obtained had good mechanical and thermal properties. The amount of the curing agent has great effect on the degree of phase segregation. In addition, with increased the curing agent amount, the thermal stabilities were also improved.

  19. Tertiary amines nucleophilicity in quaternization reaction with benzyl chloride

    Directory of Open Access Journals (Sweden)

    Ksenia S. Yutilova

    2016-03-01

    Full Text Available Quaternization reaction of tertiary amines with benzyl chloride was investigated. Reaction orders with respect to the reactants were determined. Kinetic scheme of quaternization reaction was found to be corresponding to reversible process. An influence of amines basicity and steric factor of alkyl substituent bound to the nitrogen atom on tertiary amines reactivity as nucleophiles was studied. It was shown that the rate constants of direct reaction step may serve as a measure of nucleophilicity of amines.

  20. Rh2(esp)2-catalyzed allylic and benzylic oxidations.

    Science.gov (United States)

    Wang, Yi; Kuang, Yi; Wang, Yuanhua

    2015-04-07

    The dirhodium(II) catalyst Rh2(esp)2 allows direct solvent-free allylic and benzylic oxidations by T-HYDRO with a remarkably low catalyst loading. This method is operationally simple and scalable at ambient temperature without the use of any additives. The high catalyst stability in these reactions may be attributed to a dirhodium(II,II) catalyst resting state, which is less prone to decomposition.

  1. Dethreading of Tetraalkylsuccinamide-Based [2]Rotaxanes for Preparing Benzylic Amide Macrocycles.

    Science.gov (United States)

    Martinez-Cuezva, Alberto; Rodrigues, Leticia V; Navarro, Cristian; Carro-Guillen, Fernando; Buriol, Lilian; Frizzo, Clarissa P; Martins, Marcos A P; Alajarin, Mateo; Berna, Jose

    2015-10-16

    The dethreading of a series of succinamide-based [2]rotaxanes bearing benzylic amide macrocycles is reported herein. These transformations proceeded quantitatively either under flash vacuum pyrolysis, conventional heating, or microwave irradiation. Studying the size complementarity of the stoppers at the ends of the thread and the cavity of the macrocycle allowed us to set up the best substituents for implementing the extrusion of the thread from the interlocked precursors. A variety of (1)H NMR kinetic experiments were carried out in order to evaluate the rate constants of the dethreading process, the half-life times of the rotaxanes, and the influence of temperature and solvents on these processes. The use of dibutylamino groups as stoppers yielded the rotaxane precursor in a reasonable yield and allowed the quantitative deslipping of the rotaxane. The overall process, including the rotaxane formation and its further dethreading, has been exploited for preparing benzylic amide macrocycles enhancing, in most cases, the results of the classical (2 + 2) condensation and other reported stepwise syntheses. The kinetics of the dethreading process is fairly sensitive to the electronic effects of the substituents on the isophthalamide unit or to the electronic nature of the pyridine rings through a conformational equilibrium expanding or contracting the cavity of the interlocked precursor.

  2. The Role of Vanadia for the Selective Oxidation of Benzyl Alcohol over Heteropolymolybdate Supported on Alumina

    Institute of Scientific and Technical Information of China (English)

    Pasupulet Siva Nageswara RAO; Kasanneni Tirumala Venkateswara RAO; Potharaju S. SAI PRASAD; Nakka LINGAIAH

    2011-01-01

    A series of 12-molybdophosphoric acid (MPA) supported on V2O5 dispersed γ-Al2O3 catalysts with different vanadia loadings were prepared by impregnation and characterized by N2 adsorption-desorption,X-ray diffraction,temperature-programmed reduction,in situ laser Raman spectroscopy,UV-Vis diffused reflectance spectroscopy,scanning electron microscopy,and temperature-programmed desorption of NH3 techniques.Their catalytic activities were evaluated for the vapor phase aerobic oxidation of benzyl alcohol.The catalysts exhibited high catalytic activity and the conversion of benzyl alcohol depended on the vanadia content while the catalyst with 15 wt% V2O5 content showed optimum activity.The characterization results suggest the presence of well-dispersed V2O5 and partially disintegrated Keggin ions of MPA on the support.In situ Raman studies showed a reduced Mo(IV) species when the catalysts were calcined at high temperatures.The high oxidation activity of the catalysts is related to the synergistic effect between MPA and V2O5.

  3. 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

  4. 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.

  5. 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.

  6. Cytotoxic C-benzylated chalcone and other constituents of Ellipeiopsis cherrevensis.

    Science.gov (United States)

    Wirasathien, Lalita; Pengsuparp, Thitima; Moriyasu, Masataka; Kawanishi, Kazuko; Suttisri, Rutt

    2006-06-01

    A new natural C-benzylated chalcone, 2',4'-dihydroxy-3'-(2-hydroxybenzyl)-6'-methoxychalcone (2), along with two other flavonoids, tiliroside and kaempferol 3-O-rutinoside, and an oxoaporphine alkaloid, lanuginosine were isolated from the aerial parts of Ellipeiopsis cherrevensis (Annonaceae). Two known polyoxygenated cyclohexene derivatives, ferrudiol and zeylenol, and a new analog, ellipeiopsol D, were also isolated. The chalcone 2 exhibited cytotoxic activity against human small-cell lung-cancer (NCI-H187), epidermoid carcinoma (KB) and breast cancer (BC) cell lines with IC50 values of 1.40, 5.31 and 13.92 microg/mL, respectively. This compound also showed antimalarial activity against Plasmodium falciparum with an IC50 value of 7.1 microg/mL as well as antimicrobacterial activity against Mycobacterium tuberculosis with a MIC of 25 mg/mL.

  7. Synthesis of Pharmaceutical Intermediates by Toluene Benzylation over Heteropoly Acids on Different Support

    Institute of Scientific and Technical Information of China (English)

    V. V. Bokade; G.D. Yadav

    2007-01-01

    Selective formation of pharmaceutical intermediates like diphenylmethane, dimethyldiphenylmethane, benzyl toluene and benzoic acid by liquid phase, toluene benzylation with benzyl chloride as a benzylating agent, was systematically studied over plane clay (K-10, montmorillonite),plane H-Beta, plane MFI structured titanosilicate (TS-1) and heteropoly acids [HPA, namely dodecasupported on clay, H-beta and TS-1. The 20%TPA/Clay, 30%TPA/H-Beta and 30%TPA/TS-1, were observed to be the best catalyst samples over plane clay, plane H-Beta and plane TS-1. The catalyst samples are compared with respect to benzyl chloride conversion and selectivities for diphenylmethane,dimethyl-diphenylmethane, benzyl toluene and benzoic acid. The reaction follows the pseudo-first order rate power law model. The apparent rate constants are calculated and compared with the reported ones.

  8. Friction behavior of 304 stainless steel of varying hardness lubricated with benzene and some benzyl structures

    Science.gov (United States)

    Buckley, D. H.

    1974-01-01

    The lubricating properties of some benzyl and benzene structures were determined by using 304 stainless steel surfaces strained to various hardness. Friction coefficients and wear track widths were measured with a Bowden-Leben type friction apparatus by using a pin-on-disk specimen configuration. Results obtained indicate that benzyl monosulfide, dibenzyl disulfide, and benzyl alcohol resulted in the lowest friction coefficients for 304 stainless steel, while benzyl ether provided the least surface protection and gave the highest friction. Strainhardening of the 304 stainless steel prior to sliding resulted in reduced friction in dry sliding. With benzyl monosulfide, dibenzyl disulfide, and benzyl alcohol changes in 304 stainless steel hardness had no effect upon friction behavior.

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

    OpenAIRE

    Qinggang Mei; Chun Wang; Weicheng Yuan; Guolin Zhang

    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...

  10. Aerobic dehydrogenative α-diarylation of benzyl ketones with aromatics through carbon-carbon bond cleavage.

    Science.gov (United States)

    More, Nagnath Yadav; Jeganmohan, Masilamani

    2014-02-01

    Substituted benzyl ketones reacted with aromatics in the presence of K2S2O8 in CF3COOH at room temperature, yielding α-diaryl benzyl ketones through a carbon-carbon bond cleavage. In the reaction, two new carbon-carbon bonds were formed and one carbon-carbon bond was cleaved. It is very interesting that two different nucleophiles such as benzyl ketones and aromatics were coupled together without metal, which is unusual in organic synthesis.

  11. Evaluation of activity inotropic of a new steroid derivative using an isolated rat heart model.

    Science.gov (United States)

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Bety, Sarabia-Alcocer; Landy, Campos-Ramos

    2014-01-01

    There are studies which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, a new estradiol derivative was synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of the estradiol derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; tamoxifen, prazosin, metoprolol, indomethacin and nifedipine. The results showed that the OTBDS-estradiol-hexanoic acid derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions. Additionally, other data indicate that OTBDS-estradiol-hexanoic acid derivative increase left ventricular pressure in a dose-dependent manner (0.001 to 100 nM); nevertheless, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These data suggest that positive inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative is via activation of L-type calcium channel. This phenomenon is a particularly interesting because the positive inotropic activity induced by this steroid derivative involves a molecular mechanism different in comparison with other positive inotropic drugs.

  12. Photocatalytic benzylic C–H bond oxidation with a flavin scandium complex

    OpenAIRE

    Mühldorf, Bernd; Wolf, Robert

    2015-01-01

    The enhanced reduction potential of riboflavin tetraacetate coordinating to scandium triflate enables the challenging photocatalytic C–H oxidation of electron-deficient alkylbenzenes and benzyl alcohols.

  13. New preparation of benzylic aluminum and zinc organometallics by direct insertion of aluminum powder.

    Science.gov (United States)

    Blümke, Tobias D; Groll, Klaus; Karaghiosoff, Konstantin; Knochel, Paul

    2011-12-16

    The reaction of commercial Al-powder (3 equiv) and InCl(3) (1-5 mol %) with benzylic chlorides provides various functionalized benzylic aluminum sesquichlorides under mild conditions (THF, 20 °C, 3-24 h) without homocoupling (organometallics reacted smoothly with various electrophiles (Pd-catalyzed cross-couplings, or Cu-mediated acylations, allylations, or 1,4-addition reactions). Electron-poor benzylic chlorides or substrates prone to Wurtz coupling can be converted to benzylic zinc compounds by the reaction of Al-powder in the presence of ZnCl(2).

  14. 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.

  15. Synthesis and biological evaluation of N-substituted polycyclic imides derivatives.

    Science.gov (United States)

    Bielenica, Anna; Struga, Marta; Mirosław, Barbara; Kozioł, Anna E; Kossakowski, Jerzy; Sanna, Giuseppina; La Colla, Paolo; Giliberti, Gabriele

    2013-01-01

    The preparation of 16 derivatives of 3,5,8-trioxo-4-azatricyclo- [5.2.2.0(2.6)]undec-1-yl acetate and 8 derivatives of 1-isobutoxy-4-azatricyclo[5.2.2.0(2.6)]undecane-3,5,8-trione was described. Substituents to the imide N-atom were alkyl-(aryl)piperazine fragments with an alkyl linker being propyl or butyl group. Selected newly obtained compounds were evaluated in vitro against anti-HIV-1 activity. A broad group o fderivatives were tested for their antibacterial and antifungal activity. The pharmacological properties of butyl derivatives of imide 6 were evaluated in three behavioral tests in mice. The molecular structures of starting polycyclic 6-acetyl-imides, 1 and 5, were determined by X-ray crystallography. Presented tests have not revealed any activity of the compounds, however, selected derivatives exerted no neurotoxicity in behavioral tests.

  16. Synthesis and evaluation of phenylisoserine derivatives for the SARS-CoV 3CL protease inhibitor.

    Science.gov (United States)

    Konno, Hiroyuki; Onuma, Takumi; Nitanai, Ikumi; Wakabayashi, Masaki; Yano, Shigekazu; Teruya, Kenta; Akaji, Kenichi

    2017-06-15

    Synthesis and evaluation of new scaffold phenylisoserine derivatives connected with the essential functional groups against SARS CoV 3CL protease are described. The phenylisoserine backbone was found by simulation on GOLD software and the structure activity relationship study of phenylisoserine derivatives gave SK80 with an IC50 value of 43μM against SARS CoV 3CL R188I mutant protease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Making Evaluation Work for You: Ideas for Deriving Multiple Benefits from Evaluation

    Science.gov (United States)

    Jayaratne, K. S. U.

    2016-01-01

    Increased demand for accountability has forced Extension educators to evaluate their programs and document program impacts. Due to this situation, some Extension educators may view evaluation simply as the task, imposed on them by administrators, of collecting outcome and impact data for accountability. They do not perceive evaluation as a useful…

  18. Synthesis, Anti-Tumor and Anti-Angiogenic Activity Evaluations of Asiatic Acid Amino Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Yue Jing

    2015-04-01

    Full Text Available Fifteen semi-synthetic derivatives of asiatic acid (AA have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3, while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds 4–10 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds 11–17 had significantly less effects. The new derivative 10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative 10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.

  19. [Preparation, characterization and Calu-3 cellular uptake of three kinds of poly(b-benzyl-L-amino)block-poly(ethylene glycol) nanoparticles].

    Science.gov (United States)

    Zhou, Yin; Lu, Li-Na; Xin, Xue; Huo, Dong-Feng; Wu, Hong-Bing; Qiu, Ming-Feng

    2013-04-01

    The aim of this paper is to compare the cytotoxicity and cellular uptake efficiency of three kinds of poly(b-benzyl-L-amino) block-poly(ethylene glycol) nanoparticles (PXA-PEG-NPs) using Calu-3 cells, and select one as a nasal drug delivery vector for curcumin (Cur). Poly(gamma-benzyl-L-glutamate) block-poly(ethylene glycol) nanoparticles (PBLG-PEG-NPs), poly(gamma-benzyl-L-lysine) block-poly(ethyleneglycol) nanoparticles (PZLL-PEG-NPs) and poly(gamma-benzyl-L-aspartate) block-poly(ethylene glycol) nanoparticles (PBLA-PEG-NPs) were prepared by emulsion-solvent evaporation method. MTT assays were used to evaluate the cytotoxicity of PXA-PEG-NPs against Calu-3 cells. The cellular uptake of nanoparticles was visualized by an inverted fluorescence microscope and quantified by a flow cytometer. The results indicated that even at high concentration of 2 mg x mL(-1) the three nanoparticles had no cytotoxicity on Calu-3 cells. Compared to the curcumin solution, the three curcumin-loaded PXA-PEG-NPs showed significantly higher cellular uptake efficiency on Calu-3 cells (at equal concentration of curcumin with 5 microg x mL(-1) Cur solution), PBLG-PEG-NPs group was the highest. The cellular uptake increased with incubation time, and has positive correlation with nanoparticle concentration. In brief, PXA-PEG-NPs are conducive to delivery Cur into cells, and PBLG-PEG-NPs might be provided as a good nasal drug delivery carrier.

  20. High efficient photocatalytic selective oxidation of benzyl alcohol to benzaldehyde by solvothermal-synthesized ZnIn{sub 2}S{sub 4} microspheres under visible light irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhixin, E-mail: czx@fzu.edu.cn [State Key Laboratory Breeding Base of Photocatalysis, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002 (China); Instrumental Measurement and Analysis Center, Fuzhou University, Fuzhou 350002 (China); Xu, Jingjing; Ren, Zhuyun [State Key Laboratory Breeding Base of Photocatalysis, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002 (China); He, Yunhui; Xiao, Guangcan [State Key Laboratory Breeding Base of Photocatalysis, College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002 (China); Instrumental Measurement and Analysis Center, Fuzhou University, Fuzhou 350002 (China)

    2013-09-15

    Hexagonal ZnIn{sub 2}S{sub 4} samples have been synthesized by a solvothermal method. Their properties have been determined by X-ray diffraction, ultraviolet–visible-light diffuse reflectance spectra, field emission scanning electron microscopy, nitrogen adsorption–desorption and X-ray photoelectron spectra. These results demonstrate that ethanol solvent has significant influence on the morphology, optical and electronic nature for such marigold-like ZnIn{sub 2}S{sub 4} microspheres. The visible light photocatalytic activities of the ZnIn{sub 2}S{sub 4} have been evaluated by selective oxidation of benzyl alcohol to benzaldehyde using molecular oxygen as oxidant. The results show that 100% conversion along with >99% selectivity are reached over ZnIn{sub 2}S{sub 4} prepared in ethanol solvent under visible light irradiation (λ>420 nm) of 2 h, but only 58% conversion and 57% yield are reached over ZnIn{sub 2}S{sub 4} prepared in aqueous solvent. A possible mechanism of the high photocatalytic activity for selective oxidation of benzyl alcohol over ZnIn{sub 2}S{sub 4} is proposed and discussed. - Graphical abstract: Marigold-like ZnIn{sub 2}S{sub 4} microspheres were synthesized by a solvothermal method. The high visible photocatalytic activities of ZnIn{sub 2}S{sub 4} were evaluated by selective oxidation of benzyl alcohol to benzaldehyde under mild conditions. Display Omitted - Highlights: • Marigold-like ZnIn{sub 2}S{sub 4} microspheres were synthesized by a solvothermal method. • The solvents have a remarkably influence on the morphology and properties of samples. • It is the first time to apply ZnIn{sub 2}S{sub 4} for selective oxidation of benzyl alcohol. • ZnIn{sub 2}S{sub 4} shows high photocatalytic activity for selective oxidation of benzyl alcohol.

  1. 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, pgestalt (Pearson’s r=0.35, p=0.03 and r=0.41, pgestalt ratings of online educational resources by faculty educators. Further testing is needed to ensure these instruments are accurate when applied by trainees. PMID:27625722

  2. [N-Benzyl-N-(diphenylphosphanylmethylpyridin-2-amine]chloridomethylplatinum(II

    Directory of Open Access Journals (Sweden)

    Chong-Qing Wan

    2011-01-01

    Full Text Available In the mononuclear title complex, [Pt(CH3Cl(C25H23N2P], the N-benzyl-N-(diphenylphosphanylmethylpyridin-2-amine functions as a bidentate ligand with the pyridyl N atom and the phosphine P atom chelating the PtII ion, forming a six-membered metallocycle. The PtII atom adopts a square-planar coordination geometry with one methyl group and one chloride ligand bonding to the metal center in a cis relationship. C—H...π and C—H...Cl interactions help to consolidate the packing.

  3. Efficient formation of benzylic quaternary centers via palladium catalysis.

    Science.gov (United States)

    Gottumukkala, Aditya L; Suljagic, Jasmin; Matcha, Kiran; de Vries, Johannes G; Minnaard, Adriaan J

    2013-09-01

    Four's a crowd: An efficient protocol for the formation of benzylic quaternary centers via arylation of enones using a catalyst made from Pd(O2 CCF3 )2 and 2,2'-bipyridine is developed. For cyclic substrates, catalyst loadings as low as 1 mol % Pd are enough to afford excellent yields (>90%) using a variety of arylboronic acids. In case of acyclic substrates, the addition of KSbF6 was found to improve conversions and yields. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Multireference Calculation of the Photodissociation of Benzyl Chloride

    Institute of Scientific and Technical Information of China (English)

    CAO Jun; LIU Ya-Jun; FANG Wei-Hai

    2007-01-01

    The photodissociation mechanism of benzyl chloride (BzCl) under 248 nm has been investigated by the complete active space SCF (CASSCF) method by calculating the geometries of the ground (S0) and lower excited states,the vertical (Tv) and adiabatic (T0) excitation energies of the lower states,and the dissociation reaction pathways on the potential energy surfaces (PES) of S1, T1 and T2 states.The calculated results clearly elucidated the photodissociation mechanism of BzCl,and indicated that the photodissociation on the PES of T1 state is the most favorable.

  5. {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

    1991-12-31

    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.

  6. Oxidative cleavage of benzylic C-N bonds under metal-free conditions.

    Science.gov (United States)

    Gong, Jin-Long; Qi, Xinxin; Wei, Duo; Feng, Jian-Bo; Wu, Xiao-Feng

    2014-10-14

    An interesting procedure for the oxidative cleavage of benzylic C-N bonds has been developed. Using TBAI as the catalyst and H2O2 as the oxidant, various benzylamines were transformed into their corresponding aromatic aldehydes in moderate to good yields. Notably, this is the first example of an oxidative cleavage of benzylic C-N bonds under metal-free conditions.

  7. Synthesis and biological evaluation of the pirfenidone derivatives as antifibrotic agents.

    Science.gov (United States)

    Ma, Zhen; Pan, Youlu; Huang, Wenhai; Yang, Yewei; Wang, Zunyuan; Li, Qin; Zhao, Yin; Zhang, Xinyue; Shen, Zhengrong

    2014-01-01

    A total of 24 pirfenidone derivatives were designed, synthesized and evaluated for their inhibitory activity against the human lung fibroblast cell line MRC-5. These compounds showed the remarkable proliferation inhibition against MRC-5 compared to pirfenidone as the positive control. The possible mechanism of this kind of derivatives as antifibrotic agents was explored. The molecular docking and p38 binding affinity assays demonstrated that the antifibrotic potential of the pirfenidone derivatives was possibly through the inhibition of p38 MAPK signaling pathway. The data from this study suggested that p38 might be a potential therapeutic target for the new generation antifibrotics. All the pirfenidone derivatives are reported here for the first time.

  8. Synthesis of Xylitan Derivatives and Preliminary Evaluation of in Vitro Trypanocidal Activity

    Directory of Open Access Journals (Sweden)

    Paula Regina Elias

    2016-10-01

    Full Text Available A series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. A xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. These compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against trypomastigote and amastigote forms of the parasite in T. cruzi-infected cell lineages. Benznidazole was used as positive control against T. cruzi and cytotoxicity was determined in mammalian L929 cells. The arylsulfonate xylitan derivative bearing a nitro group displayed the best activity of all the compounds tested, and was slightly more potent than the reference drug benznidazole. The importance of the isopropylidene ketal moiety was established and the greater lipophilicity of these compounds suggests enhancement in cell penetration.

  9. Synthesis, antiproliferative activities, and computational evaluation of novel isocoumarin and 3,4-dihydroisocoumarin derivatives.

    Science.gov (United States)

    Guimarães, Keller G; de Freitas, Rossimiriam P; Ruiz, Ana L T G; Fiorito, Giovanna F; de Carvalho, João E; da Cunha, Elaine F F; Ramalho, Teodorico C; Alves, Rosemeire B

    2016-03-23

    A series of novel isocoumarin derivatives were synthesized using Castro-Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different tumor cells. Furthermore, docking calculations were performed for the kallikrein 5 (KLK5) active site to predict the possible mechanism of action of this series of compounds. Theoretical findings indicate that the 3,4-dihydroisocoumarin derivative 10a forms hydrogen bonds with Ser190 and Gln192 residues of KLK5. This derivative was the most active compound in the series with potent antiproliferative activity and high selectivity index (SI > 378.79) against breast cancer cells (MCF-7, GI50 = 0.66 μg mL(-1)). This compound represents a promising matrix for developing new antiproliferative agents.

  10. Synthesis of Xylitan Derivatives and Preliminary Evaluation of in Vitro Trypanocidal Activity.

    Science.gov (United States)

    Elias, Paula Regina; Coelho, Gleicekelly Silva; Xavier, Viviane Flores; Sales Junior, Policarpo Ademar; Romanha, Alvaro José; Murta, Silvane Maria Fonseca; Carneiro, Claudia Martins; Camilo, Nilton Soares; Hilário, Flaviane Francisco; Taylor, Jason Guy

    2016-10-10

    A series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. A xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. These compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against trypomastigote and amastigote forms of the parasite in T. cruzi-infected cell lineages. Benznidazole was used as positive control against T. cruzi and cytotoxicity was determined in mammalian L929 cells. The arylsulfonate xylitan derivative bearing a nitro group displayed the best activity of all the compounds tested, and was slightly more potent than the reference drug benznidazole. The importance of the isopropylidene ketal moiety was established and the greater lipophilicity of these compounds suggests enhancement in cell penetration.

  11. Design, synthesis and biological evaluation of novel bergapten derivatives as potent lipid lowering agents

    Directory of Open Access Journals (Sweden)

    Jian-Hong Lu

    2015-03-01

    Full Text Available The aim of this study was to synthesize novel amide derivatives of bergapten and evaluate their lipid-lowering and triglyceride-lowering activities in mice. Amide derivatives of bergapten were synthesized by using lactone ring opening strategy in DMSO using NaOH as base followed by alkylation in presence of methyl iodide. The compounds were subjected to preliminary in vivo screening. Fenofibrate (30 mg/kg/day was used as positive controls in this assay. The lipid lowering activity was evaluated using in vivo Triton model and Triton WR-1339 was used as positive control. Most of the synthesized analogs displayed remarkable plasma triglyceride-lowering activity. Compound 5 showed the best activity with (41% triglyceride lowering activity. This compound also exhibited the most potent lipid lowering activity displaying 33%, 32% and 29% lowering in total cholesterol, phospholipids, and triglycerides, respectively. The other derivatives showed almost comparable activity with that of the parent molecule.

  12. Preparation and evaluation of glycosylated arginine-glycine-aspartate (RGD) derivatives for integrin targeting.

    NARCIS (Netherlands)

    Kuijpers, B.H.M.; Groothuys, S.; Soede, A.C.; Laverman, P.; Boerman, O.C.; Delft, F.L. van; Rutjes, F.P.J.T.

    2007-01-01

    Arginine-glycine-aspartate (RGD) derivatives were prepared by a combination of solid-phase and solution-phase synthesis for selective targeting of alpha vbeta 3 integrin expressed in tumors. In order to evaluate the value of a triazole moiety as a proposed amide isostere, the side chain glycosylated

  13. Synthesis and biological evaluation of andrographolide derivatives as potent anti-HIV agents

    Institute of Scientific and Technical Information of China (English)

    Bin Wang; Jing Li; Wen Long Huang; Hui Bin Zhang; Hai Qian; Yong Tang Zheng

    2011-01-01

    A series of Andro derivatives were described and evaluated for their anti-HIV activity in vitro. Compound 10 and 16b, of which TI were >10, had some anti-HTV-1 activity in vitro. Therein, compound 10 which was the best potent compound, could serve as a new lead for further development of anti-AIDS agents.

  14. Synthesis and biological evaluation of nitric oxide-releasing matrine derivatives as anticancer agents

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A series of furoxan-based nitric oxide-releasing matrine derivatives(10a-f) were synthesized.The biological evaluation showed that compounds 10a,10b,10e and 10f had stronger cytotoxic activities than 5-fluorouracil against human hepatoma cells(HepG2) in vitro.

  15. FTIR study of hydrogen bonding between substituted benzyl alcohols and acrylic esters

    Directory of Open Access Journals (Sweden)

    P. Sivagurunathan

    2016-11-01

    Full Text Available Hydrogen bonding between substituted benzyl alcohols (benzyl alcohol, o-aminobenzyl alcohol, o-chlorobenzyl alcohol and o-nitrobenzyl alcohol and acrylic esters (methyl methacrylate, ethyl methacrylate is studied in carbon tetrachloride by using the FTIR spectroscopic method. Utilizing the Nash method, the formation constant (K of the 1:1 complexes is calculated. Using the K value, the Gibbs free energy change (ΔG0 is also calculated. The calculated formation constant and Gibbs free energy change values vary with the substituent of benzyl alcohol and ester chain length, which suggests that the proton donating ability of substituted benzyl alcohols is in the order: o-aminobenzyl alcohol < benzyl alcohol < o-chlorobenzyl alcohol < o-nitrobenzyl alcohol, and proton accepting ability of acrylic esters is in the order: methyl methacrylate < ethyl methacrylate.

  16. 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 revers...

  17. Design, synthesis and hypoglycemic activity of 3-methyl-1-phe nyl-4-{ 4-[ ( 5-m et hyl-2-phenyloxazol-4-yl) methoxy ] benzylene (benzyl) }-2-pyrazol-5-one

    Institute of Scientific and Technical Information of China (English)

    Xing LIU; Yalou WANG; Guanzhong WU; Jiangchuan LI; Xiaoyan WU

    2008-01-01

    Based on the SAR (structure activity relation-ship) of TZDs (thiazolidinediones), 3-methyl-1-phenyl-2-pyrazoline-5-one was selected as a substitute for TZD. Compounds of 3-methyl- 1-phenyl-4- {4-[(5-methyl-2-phe-nyloxazol-4-yl)methoxy]benzylene(benzyl) }-2-pyrazol-5-one were designed and synthesized to find some more hypoglycemic active agents and further investigate the SAR of this class of compounds. Butanedione monoxime reacted with (substituted) benzaldehyde via cyclization and chlorination to give 4-(chloromethyl)-5-methyl-2-phenyloxazole derivatives, which condensed with 4-hydroxybenzaldehyde or vanillin, and was followed by the Knoevenagel reaction with 3-methyl-1-phenyl-2-pyrazol-5-one to give compounds Ⅰa-Ⅰh. Compounds Ⅰa-Ⅰh were hydrogenated with Pd-C to giveⅡa-Ⅱh, and their hypoglycemic activity was evaluated with a glucose oxidase kit and insulin load test on normal mice. Sixteen new target compounds were synthesized. All the com-pounds were characterized by 1H NMR, IR, MS and elemental analysis. The preliminary pharmacological tests show that the compounds have good hypoglycemic activity and can enhance the action of insulin, especially Ib, Id and If.

  18. Densities, Ultrasonic Speeds, Viscosities and Refractive Indices of Binary Mixtures of Benzene with Benzyl Alcohol,Benzonitrile, Benzoyl Chloride and Chlorobenzene at 303.15 K

    Institute of Scientific and Technical Information of China (English)

    ALI,A.; PANDEY,J.D.; SONI,N.K.; NAIN,A.K.; LAL,B.; CHAND,D.

    2005-01-01

    Densities, p, ultrasonic speeds, u, viscosities, η, and refractive indices, n, of pure benzene, benzyl alcohol (BA),benzonitrile (BN), benzoyl chloride (BC), chlorobenzene (CB) and their thirty six binary mixtures, with benzene as common component, were measured at 303.15 K over the entire mole fraction range. From these experimental data the values of deviations in ultrasonic speed, Au, isentropic compressibility, Δks, excess acoustic impedance, ZE, deviation in viscosity, Δη, and excess Gibbs free energy of activation of viscous flow, G*E, and partial molar isentropic compressibility, Kφ,2 of BA, BN, BC and CB in benzene were computed. The variation of these derived functions with composition of the mixtures suggested the increased cohesion (molecular order) in the solution and that interaction (A-B)>(A-A) or (B-B). Moreover, theoretical prediction of ultrasonic speed, viscosity and refractive index of all the four binary mixtures was made on the basis of empirical and semi-empirical relations by using the experimental values of the pure components. Comparison of theoretical results with the experimental values was made in order to assess the suitability of these relations in reproducing the experimental values of u, η and n. Also, molecular radii of pure liquids and the average molecular radii of binary mixtures were evaluated using the corresponding refractive indices of pure liquids and binary mixtures. The average molecular radii of binary mixtures were found to be additive with respect to mole fraction of the pure component.

  19. Synthesis and activity of (R)-(-)-m-trimethylacetoxy-alpha-[(methylamino)methyl]benzyl alcohol hydrochloride: a prodrug form of (R)-(-)-phenylephrine.

    Science.gov (United States)

    Yuan, S S; Bador, N

    1976-06-01

    Optically pure (R)-(-)-m-trimethylacetoxy-alpha-[(methylamino)methyl]benzyl alcohol hydrochloride was synthesized by the following sequence: (R)-(-)-phenylephrine was condensed with acetone in the presence of calcium carbide to give an oxazolidine derivative and then treated with thallous ethoxide in ether followed by trimethylacetyl chloride to yield the phenolic ester. Finally, the oxazolidine ring was cleaved by one equivalent of hydrogen chloride in ethanol. Condensation of phenylephrine with benzaldehyde, with or without solvents, gave either 1,1,2-trimethyl-4,6-dihydroxy-1,2,3,4-tetrahydroisoquinoline or a mixture of side-chain oxazolidine and the tetrahydroisoquinoline. Condensation of epinephrine with opianic acid in pyridine also gave a tetrahydroisoquinoline only. When applied on rabbit eyes, the prodrug (R)-(-)-m-trimethylacetoxy-alpha[(methylamino)methyl]benzyl alcohol hydrochloride exhibited an unexpected, three times higher mydriatic activity than the corresponding racemic prodrug and was 15 times more active than the parent, (R)-(-)-phenylephrine.

  20. 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.

  1. Evaluation of Ferrocene Derivatives as Burn Rate Modifiers in AP/HTPB-Based Composite Propellants

    Directory of Open Access Journals (Sweden)

    G. M. Gore

    1999-04-01

    Full Text Available Some ferrocene derivatives like 2,4-dinitrophenylhydrazine derivative of acetyl ferrocene, 1-pyrrolidinylmethyl ferrocene, di-ter-butyl ferrocene and 1,3-diferrocenyl-l-butene (DFB have been synthesised and characterised by infrared, nuclear magnetic resonance, ultraviolet, iron content, etc. To study the effect of their incorporation on performance, ammonium perchlorate/hydroxyl-terminated polybutadiene-based composite propellants containing these derivatives have been prepared and studied for burn rates, tensile strength and percentage elongation followed by their static test evaluation. A comparison of the properties of propellant containing solid and liquid ferrocene derivatives has been made with those containing Fe/sub 2/O/sub 3/ and n-butyl ferrocene, respectively. The data clearly indicates that these ferrocene derivatives are better than Fe/sub 2/O/sub 3/ and n-butyl errocene. Also, DFB is the best among these derivatives. Like composite propellants, DFB increases burn rate in fuel-rich propellants also.

  2. TECHNOLOGICAL EVALUATION OF CARBOXYMETHYL SESBANIA GALACTOMANNAN GUM DERIVATIVES AS THICKENERS IN REACTIVE PRINTING

    Directory of Open Access Journals (Sweden)

    Shabaan Abd El-Satar El-Khabiry

    2010-05-01

    Full Text Available Galactomannan gum isolated from the seeds of sesbania was subjected to chemical modification via carboxymethylation in non-aqueous medium using monochloroacetic acid under the catalytic action of sodium hydroxide. The obtained derivatives were subjected to measuring the degrees of substitution (D.S., rheological properties of their pastes, and evaluated as thickeners in printing cotton fabrics with reactive dyes. Highly substituted derivatives could be used successfully as thickening agents in printing cotton fabrics either alone or in admixture with sodium alginate. Prints acquire soft handle, colour strength (K/S, and fastness properties nearly identical to corresponding samples that were printed using sodium alginate.

  3. 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

  4. Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities.

    Science.gov (United States)

    Yoon, Yeong Keng; Ali, Mohamed Ashraf; Wei, Ang Chee; Choon, Tan Soo; Osman, Hasnah; Parang, Keykavous; Shirazi, Amir Nasrolahi

    2014-01-15

    A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50=58.43μM) as well as for SIRT2 (IC50=45.12μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed.

  5. Synthesis and biological evaluation of some new amide moiety bearing quinoxaline derivatives as antimicrobial agents.

    Science.gov (United States)

    Abu Mohsen, U; Yurttaş, L; Acar, U; Özkay, Y; Kaplacikli, Z A; Karaca Gencer, H; Cantürk, Z

    2015-05-01

    In this study, we aimed to synthesize some new quinoxaline derivatives bearing amide moiety and to evaluate their antimicrobial activity. A set of 16 novel compounds of N-[2,3-bis(4-methoxy/methylphenyl)quinoxalin-6-yl]-substituted benzamide derivatives were synthesized by reacting 2,3-bis(4-methoxyphenyl)-6-aminoquinoxaline or 2,3-bis(4-methylphenyl)-6-aminoquinoxaline with benzoyl chloride derivatives in tetrahydrofuran and investigated for their antimicrobial activity. The structures of the obtained final compounds were confirmed by spectral data (IR, (1)H-NMR, (13)C-NMR and MS). The antimicrobial activity of the compounds were determined by using the microbroth dilution method. Antimicrobial activity results revealed that synthesized compounds exhibited remarkable activity against Candida krusei (ATCC 6258) and Candida parapsilosis (ATCC 22019).

  6. Preparation and in vitro evaluation of benzylsulfanyl benzoxazole derivatives as potential antituberculosis agents.

    Science.gov (United States)

    Klimesová, Vera; Kocí, Jan; Waisser, Karel; Kaustová, Jarmila; Möllmann, Ute

    2009-05-01

    A set of 2-benzylsulfanyl derivatives of benzoxazole was synthesized and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis, non-tuberculous mycobacteria and multidrug-resistant M. tuberculosis. The activities were expressed as the minimum inhibitory concentration (MIC) in mmol/L. The substances showed similar activity against all tested strains. The lead compounds in the set, dinitro derivatives exhibited significant activity against both sensitive and resistant strains of M. tuberculosis and also against non-tuberculous mycobacteria. To facilitate drug design of benzoxazole as potential antituberculosis agent, we have explored the quantitative structure-activity relationship (QSAR). We demonstrated that lower lipophilicity has significant contribution to activity. Dinitrobenzylsulfanyl derivative of benzoxazole represents the promising small-molecule synthetic antimycobacterials.

  7. Discovery and Synthesis of Amino Acids Modified Deoxycholic Acid Derivatives and in Vitro Antiproliferative Evaluation.

    Science.gov (United States)

    Zhao, Chunhui; Zhao, Peizhe; Feng, Bin; Hou, Xiyan; Zhao, Longxuan

    2017-03-01

    A series of deoxycholic acid (DCA) derivatives bearing amino acid moiety has been synthesized and investigated for their potential antiproliferative activities. DCA derivative compounds were synthesized by a two or three step synthetic approach. Their bioactivities were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and Western blotting analysis on three tumor cell lines A549 (human lung cancer cell line), MCF-7 (human breast cancer cell line) and HeLa (human cervical carcinoma cell). The novel derivatives DCA3d, DCA5a, DCA5b, DCA5c, and DCA5d were found to be promising antiproliferative agents. Furthermore, DCA5b showed the greatest cytotoxic activity by induction of apoptosis. These compounds show potentiality for further optimization as antitumor drugs.

  8. Evaluation of guar gum derivatives as gelling agents for microbial culture media.

    Science.gov (United States)

    Gangotri, Waikhom; Jain-Raina, Ruchi; Babbar, Shashi B

    2012-05-01

    Guar gum, a galactomannan, has been reported to be an inexpensive substitute of agar for microbial culture media. However, its use is restricted probably because of (1) its highly viscous nature even at high temperatures, making dispensing of the media to Petri plates difficult and (2) lesser clarity of the guar gum gelled media than agar media due to impurities present in guar gum. To overcome these problems, three guar gum derivatives, carboxymethyl guar, carboxymethyl hydroxypropyl guar and hydroxypropyl guar, were tested as gelling agents for microbial growth and differentiation. These were also evaluated for their suitability for other routine microbiological methods, such as, enumeration, use of selective and differential media, and antibiotic sensitivity test. For evaluation purpose, growth and differentiation of eight fungi and eight bacteria grown on the media gelled with agar (1.5%), guar gum (4%) or one of the guar gum derivatives (4%), were compared. All fungi and bacteria exhibited normal growth and differentiation on all these media. Generally, growth of most of the fungi was better on guar gum derivatives gelled medium than on agar medium. The enumeration carried out for Serratia sp. and Pseudomonas aeruginosa by serial dilution and pour plate method yielded similar counts in all the treatments. Likewise, the selective succinate medium, specific for P. aeruginosa, did not allow growth of co-inoculated Bacillus sp. even if gelled with guar gum derivatives. The differential medium, Congo red mannitol agar could not differentiate between Agrobacterium tumefaciens and Rhizobium meliloti on color basis, if gelled with guar gum or any of its derivatives However, for antibiotic sensitivity tests for both Gram-positive and -negative bacteria, guar gum and its derivatives were as effective as agar.

  9. Theoretical Study on Sers of Wagging Vibrations of Benzyl Radical Adsorbed on Silver Electrodes

    Science.gov (United States)

    Wu, De-Yin; Chen, Yan-Li; Tian, Zhong-Qun

    2016-06-01

    Electrochemical surface-enhanced Raman spectroscopy (EC-SERS) has been used to characterize adsorbed species widely but reaction intermediates rarely on electrodes. In previous studies, the observed SERS signals were proposed from surface benzyl species due to the electrochemical reduction of benzyl chloride on silver electrode surfaces. In this work, we reinvestigated the vibrational assignments of benzyl chloride and benzyl radical as the reaction intermediate. On the basis of density functional theoretical (DFT) calculations and normal mode analysis, our systematical results provide more reasonable new assignments for both surface species. Further, we investigated adsorption configurations, binding energies, and vibrational frequency shifts of benzyl radical interacting with silver. Our calculated results show that the wagging vibration displays significant vibrational frequency shift, strong coupling with some intramolecular modes in the phenyl ring, and significant changes in intensity of Raman signals. The study also provides absolute Raman intensity in benzyl halides and discuss the enhancement effect mainly due to the binding interaction with respect to free benzyl radical.

  10. Evaluation of garnet discrimination diagrams using geochemical data of garnets derived from various host rocks

    Science.gov (United States)

    Krippner, Anne; Meinhold, Guido; Morton, Andrew C.; von Eynatten, Hilmar

    2014-06-01

    This work is an attempt to evaluate six different garnet discrimination diagrams (one binary diagram and five ternary diagrams) commonly used by many researchers. The mineral chemistry of detrital garnet is a useful tool in sedimentary provenance studies, yet there is no clear-cut understanding of what garnet type originates from which host lithology. Several discrimination diagrams exist for garnet showing distinct compositional fields, separated by strict boundaries that are thought to reflect specific types of source rocks. For this study, a large dataset was compiled (N = 3532) encompassing major element compositions of garnets derived from various host lithologies, including metamorphic, igneous, and mantle-derived rocks, in order to test the applicability of the various discrimination schemes. The dataset contains mineral chemical data collected from the literature complemented with some new data (N = 530) from garnet-bearing metamorphic and ultramafic rocks in Austria and Norway. Discrimination of the tested diagrams only works for a small group of garnets derived from mantle rocks, granulite-facies metasedimentary rocks, and felsic igneous rocks. For other garnet types, the assignment to a certain type of host rock remains ambiguous. This is considered insufficient and therefore the evaluated diagrams should be used with great care. We further apply compositional biplot analysis to derive some hints towards future perspectives in detrital garnet discrimination.

  11. Synthesis, Cytotoxicity and Mechanistic Evaluation of 4-Oxoquinoline-3-carboxamide Derivatives: Finding New Potential Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Luana da S. M. Forezi

    2014-05-01

    Full Text Available As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10–18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells.

  12. Evaluation of SEBS for Deriving Land Surface Energy Fluxes with MODIS Data in a Semiarid Region

    Science.gov (United States)

    Jayanthi, H.; Gowda, P. H.; Scanlon, B. R.; Howell, T. A.; Paul, G.

    2010-12-01

    Texas High Plains is one of the largest agricultural regions in the U.S. where 90% of the water derived from the Ogallala aquifer is used for irrigation. Accurate seasonal evapotranspiration (ET) estimates at a regional scale would be useful for groundwater management purposes. Remote sensing based ET models are suitable for this purpose. The main objective of this study was to evaluate the Surface Energy Balance System (SEBS) for its ability to estimate ET using Moderate Resolution Imaging Spectroradiometer (MODIS) data. For this purpose, the SEBS was implemented with MODIS data acquired during the 2007 crop growing season. The accuracy of the 250-m MODIS ET maps was assessed using ET data derived from Landsat Thematic Mapper (TM) images that were compared and validated against lysimetric data as part of another study and upscaled to 250 m for comparison. This presentation will discuss the statistical results and evaluate the strengths and weaknesses of the SEBS model.

  13. 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.

  14. 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.

  15. Evaluation of preservative effectiveness of p-coumaric acid derivatives in aluminium hydroxide gel-USP

    Directory of Open Access Journals (Sweden)

    Anurag Khatkar

    2013-01-01

    Full Text Available Background: Deterioration of pharmaceutical preparations due to growth of microorganisms is a great challenge and need of preservation becomes very important. Literature reports about various problems associated with the existing synthetic preservatives such as development of microbial resistance (in due course of time and several serious side effects. Aim: The aim of the present 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 p-coumaric 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 p-coumaric acid were subjected to preservative efficacy testing in an official antacid preparation, (aluminium hydroxide gel-USP 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 p- coumaric 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.

  16. New imidazolidineiminothione derivatives: Synthesis, spectral characterization and evaluation of antitumor, antiviral, antibacterial and antifungal activities.

    Science.gov (United States)

    Moussa, Ziad; El-Sharief, Marwa A M Sh; Abbas, Samir Y

    2016-10-21

    A series of new imidazolidineiminothione derivatives with various halogenated and alkylated aromatic substituents at N-(1) and at N-(3) was synthesized through the reaction of N-arylcyanothioformamides with arylisocyanate derivatives. Structure of imidazolidineiminothione derivatives were established based on spectroscopic IR, (1)H NMR, (13)C NMR, (1)H,(1)H-COSY, HSQC, (19)F NMR, MS and elemental analyses data. Evaluation of antitumor, antiviral, antibacterial and antifungal activities for the synthesized compounds were carried out to probe their activities. Most of the synthesized compounds displayed antitumor activity. The presence of 3,5-dichlorophenyl moiety at N-(1) and trichlorophenyl moiety on N-(3) (2f) resulted the highest cytotoxic activity. The presence of 9H-fluorenyl moiety on N-(3) resulted in the lowest cytotoxic activity. The antiviral screening displayed that 2d and 2f were markedly active against one or two viral strains. Compound 2d (3,5-dichlorophenyl moiety at N-(1) and 4-chlorophenyl moiety on N-(3)) showed 100% antiviral effect toward HAV. Compound 2f showed 96.7% antiviral effect toward HSV1 and 80.3% antiviral effect toward HAV. The antimicrobial activity suggested that all of the imidazolidineiminothione derivatives possess significant antimicrobial activity against most of the test organisms. Some imidazolidineiminothione derivatives showed MIC values of antibacterial and antifungal activities ranged from 0.78 to 6.25 μg/ml.

  17. Synthesis and in vitro evaluation of new diphenyl ether derivatives as serotonin transporter ligands

    Institute of Scientific and Technical Information of China (English)

    GUO YunHang; CHEN XiangJi; JIA HongMei; DEUTHER-CONRAD Winnie; BRUST Peter; STEINBACH Jorg; VERCOUILLIE Johnny; LIU BoLi

    2008-01-01

    For the development of new ligands as potential imaging agents for the serotonin transporter (SERT), a series of diphenyl ether derivatives have been synthesized, characterized, and evaluated for their in vitro binding affinities to the SERT. Among the above compounds, 2-(2-((dimethylamino)methyl)-4-fluoro-phenoxy)-5-bromobenzenamine (15) and 2-(2-((dimethylamino)methyl)-4-fluorophenoxy)-5-iodobenzene respectively. They can be further labeled with carbon-11, fluorine-18, iodine-123 or bromine-76, and evaluated as useful imaging agents for the SERT. Moreover, the study of the structure-activity relationship (SAR) provides some useful information for the future design of new ligands.

  18. Novel cycloalkylthiophene-imine derivatives bearing benzothiazole scaffold: synthesis, characterization and antiviral activity evaluation.

    Science.gov (United States)

    Ke, Shaoyong; Wei, Yanhong; Yang, Ziwen; Wang, Kaimei; Liang, Ying; Shi, Liqiao

    2013-09-15

    A series of novel cycloalkylthiophene-imine derivatives containing benzothiazole unit were designed, synthesized and evaluated for their anti-viral activities. The bio-evaluation results indicated that some of the target compounds (such as 5g, 5i, 5u) exhibited good to moderate antiviral effect on CVB5, ADV7 and EV71 viruses, however, these compounds did not have inhibition activity against H1N1 virus. Especially, the compounds 4c and 4d also exhibited high antiviral activities, which provide a new and efficient approach to evolve novel multi-functional antiviral agents by rational integration of active pharmacophores. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. 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.

  20. 1-Benzyl-3-[(trimethylsilylmethyl]benzimidazolium chloride monohydrate

    Directory of Open Access Journals (Sweden)

    Mehmet Akkurt

    2010-07-01

    Full Text Available The title compound, C18H23N2Si+·Cl−·H2O, was synthesized from 1-[(trimethylsilylmethyl]benzimidazole and benzyl chloride in dimethylformamide. The benzimidazole ring system is approximately planar, with a maximum deviation of 0.022 (2 Å, and makes an angle of 74.80 (12° with the phenyl ring. The crystal packing is stabilized by O—H...Cl, C—H...Cl, C—H...O and C—H...π interactions between symmetry-related molecules together with π–π stacking interactions between the imidazolium and benzene rings [centroid–centroid distance = 3.5690 (15 Å] and between the benzene rings [centroid–centroid distance = 3.7223 (14 Å].

  1. DNA binding properties and biological evaluation of dihydropyrimidinones derivatives as potential antitumor agents

    Science.gov (United States)

    Wang, Gongke; Li, Xiangrong; Gou, Yaping; Chen, Yuhan; Yan, Changling; Lu, Yan

    2013-10-01

    The binding properties of two medicinally important dihydropyrimidinones derivatives 5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (EMPD) and 5-(Ethoxycarbonyl)-6-methyl-4-(4-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (EMCD) with calf-thymus DNA (ctDNA) were investigated by spectroscopy, viscosity, isothermal titration calorimetry (ITC) and molecular modeling techniques. Simultaneously, their biological activities were evaluated with MTT assay method. The binding constants determined with spectroscopic titration and ITC were found to be in the same order of 104 M-1. According to the results of viscosity studies, fluorescence competitive binding experiment and ITC investigations, intercalative binding was evaluated as the dominant binding modes between the two compounds and ctDNA. Furthermore, the results of molecular modeling corroborated those obtained from spectroscopic, viscosimetric and ITC investigations. Evaluation of the antitumor activities of the two derivatives against different tumor cell lines proved that they exhibited significant tumor cell inhibition rate, accordingly blocking DNA transcription and replication. The present results favor the development of potential drugs related with dihydropyrimidinones derivatives in the treatment of some diseases.

  2. 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.

  3. Selective Aerobic Oxidation of Benzyl Alcohol Driven by Visible Light on Gold Nanoparticles Supported on Hydrotalcite Modified by Nickel Ion

    Directory of Open Access Journals (Sweden)

    Dapeng Guo

    2016-04-01

    Full Text Available A series of hydrotalcite (HT and hydrotalcite modified by the transition metal ion Ni(II was prepared with a modified coprecipitation method before being loaded with gold nanoparticles. The gold supported on Ni3Al hydrotalcite with a Ni2+/Al3+ molar ratio of 3:1 was investigated. Different techniques such as X-ray diffraction (XRD, X-ray photoelectron spectroscopy (XPS and UV-vis diffuse reflection spectrum (UV-vis DRS were applied to characterize the catalysts. A single-phase catalyst with high crystallinity, a layered structure and good composition was successfully fabricated. Good conversions and superior selectivities in the oxidation of benzyl alcohol and its derivatives were obtained with visible light due to the effect of localized surface plasmon resonance (LSPR of gold nanoparticles and the synergy of the transition metal ion Ni(II. This reaction was proven to be photocatalytic by varying the intensity and wavelength of the visible light. The catalyst can be recycled three times. A corresponding photocatalytic mechanism of the oxidation reaction of benzyl alcohol was proposed.

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

    Science.gov (United States)

    Gómez-Villarraga, Fernando; Radnik, Jörg; Martin, Andreas; Köckritz, Angela

    2016-06-01

    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.

  5. Glycosylation of a Newly Functionalized Orthoester Derivative

    Directory of Open Access Journals (Sweden)

    Kohei Kawa

    2014-02-01

    Full Text Available Tandem glycosylation of the 6-O-Fmoc-substituted benzyl orthoester derivative 2a was carried out in moderate yields by electrogenerated acid (EGA. The Fmoc group was effectively removed under mild basic conditions, and the product was submitted to the subsequent glycosylation.

  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. Evaluation of the effectiveness and safety of chitosan derivatives as adjuvants for intranasal vaccines.

    Science.gov (United States)

    Kobayashi, Takashi; Fukushima, Kenji; Sannan, Takanori; Saito, Noriko; Takiguchi, Yasuyuki; Sato, Yuko; Hasegawa, Hideki; Ishikawa, Koichi

    2013-04-01

    Intranasal immunization is currently used to deliver live virus vaccines such as influenza. However, to develop an intranasal vaccine to deliver inactivated virus, a safe and effective adjuvant is necessary to enhance the mucosal immune response. Here, we demonstrate the effectiveness of a chitosan microparticle (1-20 μm, 50 kDa, degree of deacetylation=85%) and a cationized chitosan (1000 kDa, degree of deacetylation=85%) derived from natural crab shells as adjuvants for an intranasal vaccine candidate. We examined the effectiveness of chitosan derivatives as an adjuvant by co-administering them with ovalbumin (OVA) intranasally in BALB/c mice, polymeric Ig receptor knockout (pIgR-KO) mice, and cynomolgus monkeys (Macaca fascicularis). pIgR-KO mice were used to evaluate S-IgA production on the mucosal surface without nasal swab collection. Administration of OVA with chitosan microparticles or cationized chitosan induced a high OVA-specific IgA response in the serum of pIgR-KO mice and a high IgG response in the serum of BALB/c mice and cynomolgus monkeys. We also found that administration of chitosan derivatives did not have a detrimental effect on cynomolgus monkeys as determined by complete blood count, blood chemistries, and gross pathology results. These results suggest that chitosan derivatives are safe and effective mucosal adjuvants for intranasal vaccination.

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

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    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.

  9. Synthesis, biological evaluation and SAR of sulfonamide 4-methoxychalcone derivatives with potential antileishmanial activity.

    Science.gov (United States)

    Andrighetti-Fröhner, Carla R; de Oliveira, Kely N; Gaspar-Silva, Daniela; Pacheco, Letícia K; Joussef, Antônio C; Steindel, Mário; Simões, Cláudia M O; de Souza, Alessandra M T; Magalhaes, Uiaran O; Afonso, Ilídio F; Rodrigues, Carlos R; Nunes, Ricardo J; Castro, Helena C

    2009-02-01

    Despite clinical importance of leishmaniasis, an infectious disease that affects 12 thousand million people in 88 countries, the treatment is still unsatisfactory due to its limited efficacy, cost expensive and undesirable side effects. Aiming to develop new antileishmanial lead compounds, we used a rational approach to synthesize a new set of sulfonamide 4-methoxychalcone derivatives (3a-3i) and evaluate the sulfonamide and methoxy moieties as promising adding-groups to chalcones. For that purpose we tested this new set against Leishmania braziliensis promastigotes and intracellular amastigotes and determined its cell toxicity profile. Interestingly all compounds presented a concentration-dependent antileishmanial profile and the benzylamino derivative (3i) showed a biological activity better than pentamidine. None of these compounds affected Trypanosoma cruzi epimastigotes, which suggests a specific antileishmanial profile. The structure-activity analysis of these sulfonamide 4-methoxychalcone derivatives pointed the molecular volume, the HOMO density concentrated in the chalcone moiety and the conformational structure of the compounds as important structural and stereoelectronic features for the antileishmanial activity. In addition, these compounds also fulfilled Lipinski rule of 5 and presented druglikeness similar to antileishmanial drugs. Altogether these results point the sulfonamide 4-methoxychalcone derivatives as potential lead compounds for designing new candidates for leishmaniasis treatment.

  10. 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.

  11. Selective oxidation of benzylic alcohols using copper-manganese mixed oxide nanoparticles as catalyst

    Directory of Open Access Journals (Sweden)

    Roushown Ali

    2015-07-01

    Full Text Available The catalytic activity of copper-manganese (CuMn2 mixed oxide nanoparticles (Cu/Mn = 1:2 has been studied for the selective oxidation of benzylic alcohols to the corresponding aldehydes using molecular oxygen as an oxidizing agent. The CuMn2 mixed oxide showed excellent catalytic activity for the oxidation of benzylic alcohols to the corresponding aldehydes with high selectivity (>99%. The complete conversion (100% of all the benzylic alcohols to the corresponding aldehydes is achieved within a short reaction period at 102 °C. The catalytic performance is obtained to be dependent on the electronic and steric effects of the substituents present on the phenyl ring. Electron withdrawing and bulky groups attached to the phenyl ring required longer reaction time for a complete conversion of the benzylic alcohols.

  12. A Direct Transformation of Aryl Aldehydes to Benzyl Iodides Via Reductive Iodination

    Energy Technology Data Exchange (ETDEWEB)

    Ruso, Jayaraman Sembian; Rajendiran, Nagappan; Kumaran, Rajendran Senthil [Univ. of Madras, Chennai (India)

    2014-02-15

    A facile transformation of aryl aldehydes to benzyl iodides through one-pot reductive iodination is reported. This protocol displays remarkable functional group tolerance and the title compound was obtained in good to excellent yield.

  13. Photostimulated SRN 1 Reactions of Benzyl Chloride with Carbazolyl Nitrogen Anion

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The photostimulated reactions of benzyl chloride with carbazolyl nitrogen anion in dimethyl sulfoxide gave 9-benzylcarbazole and 3-benzylcarbazole.The reactions are suggested in term of SRN1 mechanism of nucleophilic substitution.

  14. Photocatalytic oxidation of primary and secondary benzyl alcohol catalyzed by two coenzyme NAD+ models

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Photocatalytic oxidation of primary and secondary benzyl alcohol to corresponding benzaldehyde or acetophenone using Acr+ClO4- or PhAcr+ClO4- as photocatalysts under visible light irradiation at room temperature.

  15. Palladium-catalyzed Cascade Cyclization-Coupling Reaction of Benzyl Halides with N,N-Diallylbenzoylamide

    Institute of Scientific and Technical Information of China (English)

    Yi Min HU; Yu ZHANG; Jian Lin HAN; Cheng Jian ZHU; Yi PAN

    2003-01-01

    A novel type of palladium-catalyzed cascade cyclization-coupling reaction has been found. Reaction of N, N-diallylbenzoylamide 1 with benzyl halides 2 afforded the corresponding dihydropyrroles 3 in moderate to excellent yields.

  16. Polystyrene-supported Benzyl Selenide: An Efficient Reagent for Highly Stereocontrolled Synthesis of Substituted Olefins

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Polystyrene-supported benzyl selenide has been prepared. This novel reagent was treated with LDA to produce a selenium stabilized carbanion, which reacted with alkyl halide, followed by selenoxide syn-elimination, to give substituted olefins stereospecificly.

  17. Evaluation of Forest Canopy and Understory Gap Fraction Derived from Terrestrial Laser Scanning

    Science.gov (United States)

    Chen, K. C.; Wang, C. K.

    2016-06-01

    The quantification of forest carbon sequestration is helpful to understand the carbon storage on the Earth. The estimation of forest carbon sequestration can be achieved by the use of leaf area index (LAI), which is derived from forest gap fraction. The hemispherical image-based technique is the most popular non-destructive means for obtaining such information. However, only the gap fraction of the top canopy is derived due to the limitation of imaging technique. The gap fraction information of understory is thus neglected. In this study, we evaluate the use of a terrestrial laser scanner (TLS) to obtain the forest canopy and understory gap fraction. The forest TLS data were manually classified as the top canopy and understory layers to facilitate the estimation of top canopy and understory gap fraction, respectively.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Synthesis, characterization and antimicrobial evaluation of 2,5-disubstituted-4-thiazolidinone derivatives

    Directory of Open Access Journals (Sweden)

    Aakash Deep

    2014-07-01

    Full Text Available In the present study novel derivatives of 4-thiazolidinone were prepared from biphenyl-4-carboxylic acid and evaluated for their in vitro antimicrobial activity against two Gram negative strains (Escherichia coli and Pseudomonas aeruginosa and two Gram positive strains (Bacillus subtilis and Staphylococcus aureus and fungal strain Candida albicans and Aspergillus niger. The newly synthesized compounds were characterized by IR, 1H NMR and C, H, N analyses. The results revealed that all synthesized compounds have a significant biological activity against the tested microorganisms. Among the synthesized derivatives 4g (biphenyl-4-carboxylic acid [2-(3-bromophenyl-5-(3-nitrobenzylidene-4-oxo-thiazolidin-3-yl]-amide and 4i (biphenyl-4-carboxylic acid [5-(3-bromobenzylidene-2-(3-bromophenyl-4-oxo-thiazolidin-3-yl]-amide were found to be most effective antimicrobial compounds.

  3. Synthesis and pharmacological evaluation of isoxazole derivatives containing 1,2,4-triazole Moiety

    Directory of Open Access Journals (Sweden)

    Shantaram Khanage

    2012-09-01

    Full Text Available A new class of isoxazole derivatives containing 1,2,4-triazole moiety were synthesized to meet structural requirements essential for antibacterial, antimycobacterial and anticancer activity. 1-(3,5-dipheny-1H-1,2,4-triazole-1-yl ethanone (compound 2 was treated with different aromatic aldehydes to get substituted chalcones (3a-g then subsequently cyclized with hydroxyl amine hydrochloride to yield 1-[5-(substituted aryl-1,2-oxazol-3-yl]- 3,5-diphenyl-1H-1,2,4-triazoles (4a-g. IR, 1H-NMR, Mass spectra and elemental analysis were recorded to confirm the structures of target compounds. Compound 3a-g and 4a-g were screened for in vitro antimicrobial activity against B. subtillis NCIM 2063, E. coli NCIM 2065, C. albicans NCIM 3471 and A. niger NCIM 1196. MIC values were determined by liquid broth method. Chloro, nitro, methoxy substituted derivatives exhibited significant antibacterial and fungicidal potential. The in vitro antimycobacterial activity of the compounds 4a-g against Mycobacterium tuberculosis H37Rv was evaluated. The highest inhibition was observed through compound 4f as 76% at >6.25 μg/ml. Among the synthesized isoxazole derivatives, five compounds have been selected and evaluated for their anticancer activity at the National Cancer Institute for testing against a panel of approximately 60 different human tumor cell lines derived from nine neoplastic cancer types. The most efficient anticancer compound 4e was found to be active with selective influence on leukemia cancer cell lines, especially on SR with a growth % of 71.72.

  4. Synthesis Characterization and Antibacterial, Antifungal Activity of N-(Benzyl Carbamoyl or Carbamothioyl-2-hydroxy Substituted Benzamide and 2-Benzyl Amino-Substituted Benzoxazines

    Directory of Open Access Journals (Sweden)

    Tyson Belz

    2013-01-01

    Full Text Available New N-(benzyl carbamothioyl-2-hydroxy substituted benzamides 13, 20, and 21 were synthesized using sodium bicarbonate and benzyl amine with 2-thioxo-substituted-1,3-benzoxazines 6, 10a, b, 11c, and 12a–n. The 2-thioxo-substituted-1,3-oxazines 6, 10a-b, 11d 12a–n, and 26 were converted to the corresponding 2-methylthio-substituted-1,3-oxazines 14a–l and 24 which were then converted to 2-benzyl amino-substituted-benzoxazines 15a–i by refluxing with benzylamine. Products 15a, b, e, f, and g were also synthesized by boiling the corresponding N-(benzyl carbamothioyl-2-hydroxy substituted benzamides 13a, b, f, l, and m in acetic acid. 2-Oxo-substituted-1,3-benzoxazines 22 and 25 were prepared by treating the corresponding 2-methylthio-substituted-1,3-oxazines 14 and 24 with dilute HCl. The N-(benzyl carbamoyl-2-hydroxy substituted benzamide 23 was synthesized from the reaction of 2-oxo-substituted-1,3-benzoxazine 22 with benzylamine. The new products were characterized using IR, 1H, and 13C NMR in addition to microanalysis. Selected compounds were tested in vitro for antibacterial and antifungi activity and the most active compounds were found to be the 4-(substituted-benzylamino-2-hydroxy benzoic acids 9a and d (M. chlorophenolicum, MIC 50 and 25 µgm L−1, resp., N1, N3-bis (benzyl carbamothioyl-4,6-dihydroxy-substituted phthalamides 20a and 20c (B. subtilis MIC 12.5, 50 µgm L−1, resp. and 21 (M. chlorophenolicum, MIC 50 µgm L−1.

  5. Glycosidic aroma precursors of 2-phenylethyl and benzyl alcohols from Jasminum sambac flowers.

    Science.gov (United States)

    Inagaki, J; Watanabe, N; Moon, J H; Yagi, A; Sakata, K; Ina, K; Luo, S

    1995-04-01

    Benzyl 6-O-beta-D-xylopyranosyl-beta-D-glucopyranoside (beta-primeveroside) (1), 2-phenylethyl beta-primeveroside (2), and 2-phenylethyl 6-O-alpha-L-rhamnopyranosyl-beta-D-glucopyranoside (beta-rutinoside) (3) were isolated as aroma precursors of benzyl alcohol and 2-phenylethanol from flower buds of Jasminum sambac Ait. The isolation was guided by an enzymatic hydrolysis and GC and GC-MS analyses.

  6. 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] 

  7. Syntheses, Characterization and Antimicrobial Evaluation of Some 1, 3, 5-Trisubustituted Pyrazole Derivatives

    Directory of Open Access Journals (Sweden)

    Vertika Gautam

    2010-01-01

    Full Text Available A series of 1, 3, 5-trisubustituted pyrazole derivatives were synthesized and screened for antimicrobial activity. The compounds (2j-o were evaluated against two gram-positive and two gram-negative bacteria and one fungus, at concentrations of 10 µg/mL and 50 µg/mL. The compounds were founds to be inactive against P. aeruginosa and A. niger but exhibited moderate activity against B. subtilis, E. coli and S. aureus. It can be concluded that the newly synthesized compounds possess promising antimicrobial activity.

  8. Synthesis and herbicidal evaluation of novel benzothiazole derivatives as potential inhibitors of D1 protease.

    Science.gov (United States)

    Huang, Tonghui; Sun, Jie; An, Lin; Zhang, Lixian; Han, Cuiping

    2016-04-01

    D1 protease is a C-terminal processing protease that has been predicted to be an ideal herbicidal target. Three novel series of benzothiazole derivatives were synthesized and evaluated for their herbicidal activities against Brassica napus (rape) and Echinochloa crusgalli (barnyard grass). The preliminary bioassay indicated that most of the synthesized compounds possess promising D1 protease inhibitory activities and considerable herbicidal activities. Molecular docking was performed to position representative compounds into the active site of D1 protease to determine a probable binding model.

  9. Synthesis, in vitro evaluation, and docking studies of novel chromone derivatives as HIV-1 protease inhibitor

    Science.gov (United States)

    Ungwitayatorn, Jiraporn; Wiwat, Chanpen; Samee, Weerasak; Nunthanavanit, Patcharawee; Phosrithong, Narumol

    2011-08-01

    Novel chromone derivatives with a benzopyran-4-one scaffold have been prepared by the one-pot cyclization reaction. The in vitro inhibitory activity of these new compounds towards HIV-1 protease have been evaluated using stop time HPLC method as the preliminary screening. The most potent compound, 7,8-dihydroxy-2-(3'-trifluoromethyl phenyl)-3-(3″-trifluoromethylbenzoyl)chromone ( 32), showed IC 50 = 0.34 μM. The molecular docking study supported results from experimental activity testing and also provided structure-activity relationship of this series.

  10. Synthesis of New Indole Derivatives Structurally Related to Donepezil and Their Biological Evaluation as Acetylcholinesterase Inhibitors

    Directory of Open Access Journals (Sweden)

    Samar I. Faggal

    2012-04-01

    Full Text Available New series of indole derivatives analogous to donepezil, a well known anti-Alzheimer and acetylcholinesterase inhibitor drug, was synthesized. A full chemical characterization of the new compounds is provided. Biological evaluation of the new compounds as acetylcholinesterase inhibitors was performed. Most of the compounds were found to have potent acetylcholinesterase inhibitor activity compared to donepezil as standard. The compound 1-(2-(4-(2-fluorobenzyl piperazin-1-ylacetylindoline-2,3-dione (IIId was found to be the most potent.

  11. Rational Design, Synthesis and Evaluation of Coumarin Derivatives as Protein-protein Interaction Inhibitors.

    Science.gov (United States)

    De Luca, Laura; Agharbaoui, Fatima E; Gitto, Rosaria; Buemi, Maria Rosa; Christ, Frauke; Debyser, Zeger; Ferro, Stefania

    2016-09-01

    Herein we describe the design and synthesis of a new series of coumarin derivatives searching for novel HIV-1 integrase (IN) allosteric inhibitors. All new obtained compounds were tested in order to evaluate their ability to inhibit the interaction between the HIV-1 IN enzyme and the nuclear protein lens epithelium growth factor LEDGF/p75. A combined approach of docking and molecular dynamic simulations has been applied to clarify the activity of the new compounds. Specifically, the binding free energies by using the method of molecular mechanics-generalized Born surface area (MM-GBSA) was calculated, whereas hydrogen bond occupancies were monitored throughout simulations methods.

  12. 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.

  13. Evaluation of deriving fire cycle of forested landscape based on time-since-fire distribution

    Institute of Scientific and Technical Information of China (English)

    ZHANG Quan-fa; Kurt S. Pregitzer; JIANG Ming-xi; CHEN Wen-jun

    2006-01-01

    Estimation of fire cycle has been conducted by using the negative exponential function as an approximation of time-since-fire distribution of a landscape assumed .to be homogeneous with respect to fire spread processes. The authors imposed predefined fire cycles on a virtual landscape of 100 cell ×100 cell, and obtained a mosaic composing of patches with different stand ages (i.e. time since fire). Graphical and statistical methods (Van Wagner 1978; Reed et al. 1998) were employed to derive fire cycle from the virtual landscape. By comparing the predefined and the derived fire cycles, the two methods and tested the effects of sample size and hazard of burning (i.e., stand's susceptibility to fire in relation to its stand age) were evaluated on fire cycle deviation. The simulation results indicated a minimum sample size of 10 times of the annual burnt area would be required for partitioning time-since-fire distribution into homogeneous epochs indicating temporal change in fire cycle. Statistically, there was significant difference among the imposed and the derived fire cycle, regardless of sample sizes with or without consideration of hazard of burning. Both methods underestimated the more recent fire cycle without significant difference between them. The results imply that deviation of fire cycle based on time-since-fire distribution warrants cautious interpretation, especially when a landscape is spatially partitioned into small units and temporal changes in fire cycle are involved.

  14. Evaluation on the inhibition of pyrrol-2-yl ethanone derivatives to lactate dehydrogenase and anticancer activities

    Science.gov (United States)

    Lu, Na-Na; Weng, Zhao-Yue; Chen, Qiu-Yun; Boison, Daniel; Xiao, Xin-Xin; Gao, Jing

    2016-08-01

    Lactate dehydrogenase A (LDH-A) is a potentially important metabolic target for the inhibition of the highly activated glycolysis pathway in cancer cells. In order to develop bifunctional compounds as inhibitor of LDH-A and anticancer agents, two pyrrol-2-yl methanone (or ethanone) derivatives (PM1 and PM2) were synthesized and evaluated as inhibitors of LDH-A based on the enzyme assay and cell assay by spectroscopy analysis. Fluorescence and CD spectra results demonstrated that both the change of second structure of LDH-A and the affinity interaction for compounds to LDH-A gave great effect on the activity of LDH-A. In particular, low concentration of compounds (1 μμ-25 μμ) could change the level of pyruvate in cancer cells. Moreover, the in vitro assay results demonstrated that pyrrol-2-yl ethanone derivatives can inhibit the proliferation of cancer cells. Therefore, pyrrol-2-yl ethanone derivatives (PM2) can be both LDH-A inhibitor and anticancer agents.

  15. Antioxidant Activity of Diphenylpropionamide Derivatives: Synthesis, Biological Evaluation and Computational Analysis

    Directory of Open Access Journals (Sweden)

    Giuseppina Tommonaro

    2008-03-01

    Full Text Available We report the synthesis, antioxidant and antiproliferative activity and a QSARanalysis of synthetic diphenylpropionamide derivatives. Synthesis of these compounds wasachieved by direct condensation of 2,2- and 3,3-diphenylpropionic acid and appropriateamines using 1-propylphoshonic acid cyclic anhydride (PPAA as catalyst. Compoundstructures were elucidated by NMR analysis and their melting points were measured. Thein vitro antioxidant activity of these compounds was tested by evaluating the amount ofscavenged ABTS radical and estimating ROS and NO production in LPS stimulatedJ774.A1 macrophages. All compounds were tested for their effect on viability of cells andresults demonstrated that they are not toxic towards the cell lines used. The cytotoxicactivity of all compounds was evaluated by a Brine Shrimp Test.

  16. Synthesis and in vitro evaluation of new diphenyl ether derivatives as serotonin transporter ligands

    Institute of Scientific and Technical Information of China (English)

    DEUTHER-CONRAD; Winnie; BRUST; Peter; STEINBACH; Jrg; VERCOUILLIE; Johnny

    2008-01-01

    For the development of new ligands as potential imaging agents for the serotonin transporter (SERT),a series of diphenyl ether derivatives have been synthesized,characterized,and evaluated for their in vitro binding affinities to the SERT. Among the above compounds,2-(2-((dimethylamino)methyl)-4-fluoro-phenoxy)-5-bromobenzenamine (15) and 2-(2-((dimethylamino)methyl)-4-fluorophenoxy)-5-iodobenzene amine (16) show high binding affinities for the SERT with Ki values of 0.28 and 0.20 nmol·L-1,respectively. They can be further labeled with carbon-11,fluorine-18,iodine-123 or bromine-76,and evaluated as useful imaging agents for the SERT. Moreover,the study of the structure-activity relationship (SAR) provides some useful information for the future design of new ligands.

  17. Synthetic chalcone derivatives as inhibitors of cathepsins K and B, and their cytotoxic evaluation.

    Science.gov (United States)

    Ramalho, Suelem Demuner; Bernades, Aline; Demetrius, Giulio; Noda-Perez, Caridad; Vieira, Paulo Cezar; Dos Santos, Caio Yu; da Silva, James Almada; de Moraes, Manoel Odorico; Mousinho, Kristiana Cerqueira

    2013-11-01

    A series of chalcone derivatives, 1-15, were prepared by Claisen-Schmidt condensation and evaluated for their cytotoxicities on tumor cell lines and also against proteolytic enzymes such as cathepsins B and K. Of the compounds synthesized, (E)-3-(3,4-dimethoxyphenyl)-1-phenylprop-2-en-1-one (12), (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (13), (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (14), and (E)-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one (15) showed significant cytotoxicities. The most effective compound was 15, which showed high cytotoxic activity with an IC50 value lower than 1 μg/ml, and no selectivity on the tumor cells evaluated. Substituents at C(4) of ring B were found to be essential for cytotoxicity. In addition, it was also demonstrated that some of these chalcones are moderate inhibitors of cathepsin K and have no activity against cathepsin B.

  18. Selective oxidation of benzyl alcohol with tert-butylhydroperoxide catalysed via Mn (II) 2, 2-bipyridine complexes immobilized over the mesoporous hexagonal molecular sieves (HMS)

    Indian Academy of Sciences (India)

    Vahid Mahdavi; Mahdieh Mardani

    2012-09-01

    A series ofMn(II)bipy complexes with different loading of Mn2+ supported on HMS was prepared. These samples were characterized by Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), Thermogravimetric and Differential Scanning Calorimetry (TG-DSC), Ultraviolet and Visible spectra (UV-Vis) and Fourier transforms Infrared (FT-IR). The catalytic activity of the supportedMn(II)bipy complexes, [Mn(bipy)2]2+/HMS was evaluated in the oxidation of benzyl alcohol in the liquid phase using tert-butylhydroperoxide (TBHP) as an oxidant. The effects of Mn2+ loading and various solvents on the conversion and selectivity were studied. A second order function for the variation in catalytic activity with respect to the loading of Mn2+ ions in different catalyst samples was observed. The activity of the [Mn(bipy)2]2+/HMS catalyst differs with the type of the solvent and in this case, acetonitrile gives the best conversion results. The kinetic of benzyl alcohol oxidation was investigated at temperatures of 27, 46, 60, 75 and 90°C using [Mn(bipy)2]2+/HMS and excess TBHP. The order of reaction with respect to benzyl alcohol was determined to be pseudo-first order. The value of the apparent activation energy was also determined.

  19. Design, synthesis, and biological evaluation of phosphoramide derivatives as urease inhibitors.

    Science.gov (United States)

    Domínguez, María J; Sanmartín, Carmen; Font, María; Palop, Juan A; San Francisco, Sara; Urrutia, Oscar; Houdusse, Fabrice; García-Mina, José

    2008-05-28

    The design, synthesis, and biological evaluation of phosphoramide derivatives as urease inhibitors to reduce the loss of ammonia has been carried out. Forty phosphorus derivatives were synthesized and their inhibitory activities evaluated against that of jack bean urease. In addition, in vivo assays have been carried out. All of the compounds were characterized by IR, (1)H NMR, MS, and elemental microanalysis. In some cases, detailed molecular modeling studies were carried out, and these highlighted the interaction between the enzyme active center and the compounds and also the characteristics related to their activity as urease inhibitors. According to the IC(50) values for in vitro inhibitory activity, 12 compounds showed values below 1 microM and 8 of them represent improvements of activity in comparison to the commercial urease inhibitor N-n-butylthiophosphorictriamide (NBPT) (100 nM) (AGROTAIN). On the basis of the activity results and the conclusions of the molecular modeling study, a structural model for new potential inhibitors has been defined.

  20. Mesenchymal Stem Cell-Derived Exosomes: Immunomodulatory Evaluation in an Antigen-Induced Synovitis Porcine Model

    Science.gov (United States)

    Casado, Javier G.; Blázquez, Rebeca; Vela, Francisco Javier; Álvarez, Verónica; Tarazona, Raquel; Sánchez-Margallo, Francisco Miguel

    2017-01-01

    Synovitis is an inflammatory process associated with pain, disability, and discomfort, which is usually treated with anti-inflammatory drugs or biological agents. Mesenchymal stem cells (MSCs) have been also successfully used in the treatment of inflammatory-related diseases such as synovitis or arthritis. In the last years, the exosomes derived from MSCs have become a promising tool for the treatment of inflammatory-related diseases and their therapeutic effect is thought to be mediated (at least in part) by their immunomodulatory potential. In this work, we aimed to evaluate the anti-inflammatory effect of these exosomes in an antigen-induced synovitis animal model. To our knowledge, this is the first report where exosomes derived from MSCs have been evaluated in an animal model of synovitis. Our results demonstrated a decrease of synovial lymphocytes together with a downregulation of TNF-α transcripts in those exosome-treated joints. These results support the immunomodulatory effect of these exosomes and point out that they may represent a promising therapeutic option for the treatment of synovitis.

  1. Field evaluation of potential fruit-derived lures for Anastrepha obliqua (Diptera: Tephritidae).

    Science.gov (United States)

    Toledo, Jorge; Malo, Edi A; Cruz-López, Leopoldo; Rojas, Julio C

    2009-12-01

    Previous studies have shown that a nine-component blend (ethyl butyrate, isopropyl butyrate, hexan-1-ol, propyl butyrate, isobutyl butyrate, ethyl hexanoate, isopentyl butyrate, ethyl benzoate, and ethyl octanoate) isolated from Spondias mombin L. (Anacardiaceae) fruit are attractive to both sexes of West Indian fruit fly, Anastrepha obliqua (Macquart) (Diptera: Tephritidae), in laboratory and field cage tests. In this study, we evaluated the effectiveness of traps baited with the nine-component blend in capturing wild A. obliqua in a mango, Mangifera indica L. variety Ataulfo) orchard. In addition, we tested other S. mombin-derived lures to determine whether any of these effectively mimic the nine-component blend in attracting A. obliqua. In all trials, we compared the attractiveness of the S. mombin-derived lures against hydrolyzed protein, the standard bait for monitoring A. obliqua. We found that, in some trials, there was no difference in the number of females caught by traps baited with the nine-component blend or with hydrolyzed protein. In other trials, traps baited with hydrolyzed protein captured more females than traps baited with the nine-component blend. For males, in general there were no differences in the number of flies caught by traps baited either with the nine-component blend or with hydrolyzed protein. Traps baited with other S. mombin-derived lures captured fewer A. obliqua than traps baited with hydrolyzed protein. Traps baited with S. mombin-derived lures caught fewer species of nontarget tephritid flies and nontarget insects than traps baited with hydrolyzed protein.

  2. Design, synthesis and biological evaluation of negatively charged ¹¹¹In-DTPA-octreotide derivatives.

    Science.gov (United States)

    Oshima, Nobuhiro; Akizawa, Hiromichi; Zhao, Songji; Zhao, Yan; Nishijima, Ken-ichi; Kitamura, Yoji; Arano, Yasushi; Kuge, Yuji; Ohkura, Kazue

    2014-02-15

    Our previous studies indicated that (111)In-diethylenetriaminepentaacetic acid ((111)In-DTPA)-octreotide derivatives with an additional negative charge by replacing N-terminal d-phenylalanine (d-Phe) with an acidic amino acid such as l-aspartic acid (Asp) or its derivative exhibited low renal radioactivity levels when compared with (111)In-DTPA-D-Phe(1)-octreotide. On the basis of the findings, we designed, synthesized and evaluated two Asp-modified (111)In-DTPA-conjugated octreotide derivatives, (111)In-DTPA-Asp(1)-octreotide and (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide. While (111)In-DTPA-Asp(1)-octreotide showed negligible AR42J cell uptake, (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited AR42J cell uptake similar to that of (111)In-DTPA-D-Phe(1)-octreotide. When administered to AR42J tumor-bearing mice, (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited renal radioactivity levels significantly lower than did (111)In-DTPA-D-Phe(1)-octreotide at 1 and 3 h post-injection. No significant differences were observed in tumor accumulation between (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide and (111)In-DTPA-D-Phe(1)-octreotide after 1 and 3h injection. The findings in this study suggested that an interposition of an Asp at an appropriate position in (111)In-DTPA-D-Phe(1)-octreotide would constitute a useful strategy to develop (111)In-DTPA-D-Phe(1)-octreotide derivatives of low renal radioactivity levels while preserving tumor accumulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Pentanol and Benzyl Alcohol Attack Bacterial Surface Structures Differently

    Science.gov (United States)

    Yano, Takehisa; Miyahara, Yoshiko; Morii, Noriyuki; Okano, Tetsuya

    2015-01-01

    The genus Methylobacterium tolerates hygiene agents like benzalkonium chloride (BAC), and infection with this organism is an important public health issue. Here, we found that the combination of BAC with particular alcohols at nonlethal concentrations in terms of their solitary uses significantly reduced bacterial viability after only 5 min of exposure. Among the alcohols, Raman spectroscopic analyses showed that pentanol (pentyl alcohol [PeA]) and benzyl alcohol (BzA) accelerated the cellular accumulation of BAC. Fluorescence spectroscopic assays and morphological assays with giant vesicles indicated that PeA rarely attacked membrane structures, while BzA increased the membrane fluidity and destabilized the structures. Other fluorescent spectroscopic assays indicated that PeA and BzA inactivate bacterial membrane proteins, including an efflux pump for BAC transportation. These findings suggested that the inactivation of membrane proteins by PeA and BzA led to the cellular accumulation but that only BzA also enhanced BAC penetration by membrane fluidization at nonlethal concentrations. PMID:26519389

  4. EFSA EFSA ; Scientific Opinion on Flavouring Group Evaluation 99 (FGE.99): Consideration of furanone derivatives evaluated by the JECFA (63rd, 65th and 69th meetings)

    DEFF Research Database (Denmark)

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

    evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of five furanone derivatives evaluated by the JECFA at their 63rd, 65th and 69th meetings. The substances were evaluated through a stepwise approach that integrates information...

  5. Automated Electrophysiological and Pharmacological Evaluation of Human Pluripotent Stem Cell-Derived Cardiomyocytes

    Science.gov (United States)

    Rajamohan, Divya; Kalra, Spandan; Duc Hoang, Minh; George, Vinoj; Staniforth, Andrew; Russell, Hugh; Yang, Xuebin

    2016-01-01

    Automated planar patch clamp systems are widely used in drug evaluation studies because of their ability to provide accurate, reliable, and reproducible data in a high-throughput manner. Typically, CHO and HEK tumorigenic cell lines overexpressing single ion channels are used since they can be harvested as high-density, homogenous, single-cell suspensions. While human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are physiologically more relevant, these cells are fragile, have complex culture requirements, are inherently heterogeneous, and are expensive to produce, which has restricted their use on automated patch clamp (APC) devices. Here, we used high efficiency differentiation protocols to produce cardiomyocytes from six different hPSC lines for analysis on the Patchliner (Nanion Technologies GmbH) APC platform. We developed a two-step cell preparation protocol that yielded cell catch rates and whole-cell breakthroughs of ∼80%, with ∼40% of these cells allowing electrical activity to be recorded. The protocol permitted formation of long-lasting (>15 min), high quality seals (>2 GΩ) in both voltage- and current-clamp modes. This enabled density of sodium, calcium, and potassium currents to be evaluated, along with dose–response curves to their respective channel inhibitors, tetrodotoxin, nifedipine, and E-4031. Thus, we show the feasibility of using the Patchliner platform for automated evaluation of the electrophysiology and pharmacology of hPSC-CMs, which will enable considerable increase in throughput for reliable and efficient drug evaluation. PMID:26906236

  6. Polyvinylpyrrolidone-bromine complex: An efficient polymeric reagent for selective preparation of benzyl bromides in the presence of hexamethyldisilane

    Directory of Open Access Journals (Sweden)

    Moslem M. Lakouraj

    2012-08-01

    Full Text Available Benzylic bromides were conveniently obtained in high yields via the reaction of the corresponding alcohols with crosslinked polyvinylpyrrolidone-bromine complex (PVPP-Br2/hexamethyldisilane in chloroform at reflux condition. Selective conversion of benzyl alcohol to benzyl bromide in the presence of primary aliphatic alcohols, e.g. 2-phenylethanol was also achieved.DOI: http://dx.doi.org/10.4314/bcse.v26i2.14

  7. Evaluation of cytotoxic effects of several novel tetralin derivatives against Hela, MDA-MB-468, and MCF-7 cancer cells

    Directory of Open Access Journals (Sweden)

    Fateme Shafiee

    2012-01-01

    Conclusion: With the exception of compound 2, other tested compounds have potential for further cytotoxicity evaluation. Synthesizing other tetralin derivatives similar to compound 4 and studying their structure-activity relationships (SARs would be encouraged.

  8. 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.

  9. Efficient Catalytic Oxidation of 3-Arylthio- and 3-Cyclohexylthio-lapachone Derivatives to New Sulfonyl Derivatives and Evaluation of Their Antibacterial Activities

    Directory of Open Access Journals (Sweden)

    Mariana F. do C. Cardoso

    2017-02-01

    Full Text Available New sulfonyl-lapachones were efficiently obtained through the catalytic oxidation of arylthio- and cyclohexylthio-lapachone derivatives with hydrogen peroxide in the presence of a Mn(III porphyrin complex. The antibacterial activities of the non-oxidized and oxidized lapachone derivatives against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus were evaluated after their incorporation into polyvinylpyrrolidone (PVP micelles. The obtained results show that the PVP-formulations of the lapachones 4b–g and of the sulfonyl-lapachones 7e and 7g reduced the growth of S. aureus.

  10. In Vitro Evaluation of the Antimicrobial Ability and Cytotoxicity on Two Melanoma Cell Lines of a Benzylamide Derivative of Maslinic Acid

    Science.gov (United States)

    Dehelean, Cristina Adriana; Muntean, Delia; Csuk, René

    2016-01-01

    Maslinic acid is a pentacyclic triterpene extracted from olives that has been systematically reported to exert several therapeutic effects, such as antitumoral, antidiabetic, antioxidant, anti-inflammatory, antiparasitic, and antiviral properties. Recently, new derivatives of maslinic acid have been obtained and expanded the spectrum of biological activities and improved the existing ones. The present study was meant to perform the in vitro assessment of the (i) cytotoxic effects of a benzylamide derivative of maslinic acid (“EM2”) (benzyl (2α, 3β) 2,3-diacetoxy-olean-12-en-28-amide) on B164A5 murine melanoma and A375 human malignant melanoma cell lines and the (ii) antimicrobial activity of the compound on several bacterial strains, respectively. We obtained a dose-dependent cytotoxic effect of EM2 that was particularly relevant to the murine cell line. As on the antibacterial activity, EM2 was tested on 10 bacterial strains Bacillus cereus, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, Escherichia coli, Yersinia enterocolitica, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa and one fungus Candida albicans. A significant antimicrobial effect was recorded for Streptococcus pyogenes and Staphylococcus aureus. PMID:28050335

  11. In Vitro Evaluation of the Antimicrobial Ability and Cytotoxicity on Two Melanoma Cell Lines of a Benzylamide Derivative of Maslinic Acid

    Directory of Open Access Journals (Sweden)

    Ioana Zinuca Pavel

    2016-01-01

    Full Text Available Maslinic acid is a pentacyclic triterpene extracted from olives that has been systematically reported to exert several therapeutic effects, such as antitumoral, antidiabetic, antioxidant, anti-inflammatory, antiparasitic, and antiviral properties. Recently, new derivatives of maslinic acid have been obtained and expanded the spectrum of biological activities and improved the existing ones. The present study was meant to perform the in vitro assessment of the (i cytotoxic effects of a benzylamide derivative of maslinic acid (“EM2” (benzyl (2α, 3β 2,3-diacetoxy-olean-12-en-28-amide on B164A5 murine melanoma and A375 human malignant melanoma cell lines and the (ii antimicrobial activity of the compound on several bacterial strains, respectively. We obtained a dose-dependent cytotoxic effect of EM2 that was particularly relevant to the murine cell line. As on the antibacterial activity, EM2 was tested on 10 bacterial strains Bacillus cereus, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, Escherichia coli, Yersinia enterocolitica, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa and one fungus Candida albicans. A significant antimicrobial effect was recorded for Streptococcus pyogenes and Staphylococcus aureus.

  12. Fast numerical evaluation of time-derivative non-adiabatic couplings for mixed quantum-classical methods

    CERN Document Server

    Ryabinkin, Ilya G; Izmaylov, Artur F

    2015-01-01

    We have developed a numerical differentiation scheme which eliminates evaluation of overlap determinants in calculating the time-derivative non-adiabatic couplings (TDNACs). Evaluation of these determinants was a bottleneck in previous implementations of mixed quantum-classical methods using numerical differentiation of electronic wave functions in the Slater-determinant representation. The central idea of our approach is, first, to reduce the analytic time derivatives of Slater determinants to time derivatives of molecular orbitals, and then to apply a finite-difference formula. Benchmark calculations prove the efficiency of the proposed scheme showing impressive several-order-of-magnitude speedups of the TDNAC calculation step for midsize molecules.

  13. Evaluation of anti-inflammatory, analgesic activities, and side effects of some pyrazole derivatives.

    Science.gov (United States)

    Domiati, Souraya; El-Mallah, Ahmed; Ghoneim, Asser; Bekhit, Adnan; El Razik, Heba Abd

    2016-08-01

    Non-steroidal anti-inflammatory drugs are associated with several side effects, such as gastrointestinal mucosal damage, renal toxicity, and cardiovascular side effects. Aiming to find a novel analgesic/anti-inflammatory drug with minimal side effects, the present study was designed to screen and evaluate some newly synthesized pyrazole derivatives. Anti-inflammatory activity using carrageenan-induced rat paw edema and cotton-pellet-induced granuloma, COX-1/COX-2 selectivity using thin layer chromatography, and analgesic using hot plate and tail flick tests as well as ulcerogenic and renal side effects of the ten compounds were assessed. The results of the carrageenan-induced rat paw edema showed that the carboxyphenylhydrazone derivative (N9) was more potent than the chlorophenyl counterpart (N8) with a relative activity compared to celecoxib of 1.08 and -0.13, respectively, after 1 h. Even though this is true, N9 caused significant increase in the ulcer index, creatinine, and Blood Urea Nitrogen levels. The cotton granuloma test showed that the carboxyphenylhydrazone derivative (N7) was also more potent than its chlorophenyl counterpart (N6) with a relative activity compared to celecoxib of 1.13 and 0.86, respectively. Moreover, adding an acetyl not only increased the anti-inflammatory activity from a relative activity compared to celecoxib of 0.57-1.17 for the compounds X4 and N5, respectively, in the granuloma test, but also increased the selectivity toward COX-2 from 0.197 to 47.979. As a conclusion, from the ten compounds analyzed, N5 and N7 showed promising results as anti-inflammatory/analgesic agents with low ulcerogenicity and nephrotoxicity and thus should be further analyzed to determine the ED50 and other side effects.

  14. 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.

  15. Natural product derived antiprotozoal agents: synthesis, biological evaluation, and structure-activity relationships of novel chromene and chromane derivatives.

    Science.gov (United States)

    Harel, Dipak; Schepmann, Dirk; Prinz, Helge; Brun, Reto; Schmidt, Thomas J; Wünsch, Bernhard

    2013-09-26

    Various natural products with the chromane and chromene scaffold exhibit high antiprotozoal activity. The natural product encecalin (7) served as key intermediate for the synthesis of different ethers 9, amides 11, and amines 12. The chromane analogues 14 and the phenols 15 were obtained by reductive amination of ketones 13 and 6, respectively. Angelate 3, ethers 9, and amides 11 did not show considerable antiprotozoal activity. However, the chromene and chromane derived amines 12, 14, and 15 revealed promising antiprotozoal activity and represent novel lead compounds. Whereas benzylamine 12a and α-methylbenzylamine 12g were active against P. falciparum with IC50 values in the range of chloroquine, the analogous phenols 15a and 15b were unexpectedly 10- to 25-fold more potent than chloroquine with selectivity indexes of 6760 and 1818, respectively. The phenylbutylamine 14d based on the chromane scaffold has promising activity against T. brucei rhodesiense and L. donovani.

  16. Podophyllotoxin-derived insecticidal agents: part XIII--evaluation of insecticidal activity of podophyllotoxin derivatives against Brontispa longissima.

    Science.gov (United States)

    Liu, Ying-Qian; Feng, Gang; Yang, Liu; Jing-Zhang; Li, Hong-Yu

    2011-09-01

    In an attempt to find the biorational insecticides for Brontispa longissima control, 12 podophyllotoxin (PPT) analogues were tested for their insecticidal activity against the fifth-instar larvae of B. longissima in vivo for the first time. Among all the tested compounds, especially compounds 6 and 8 showed more promising and pronounced insecticidal activity than toosendanin, a commercial insecticide derived from Melia azedarach. The different insecticidal activity range of compounds 1-12 indicated that the variation of chemical structures in the PPT skeleton markedly affected the activity profiles of this compound class, and some important structure-activity relationship information has been revealed. Together, these preliminary results may be useful in guiding further modification of PPTs in the development of potential new insecticides.

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

    Science.gov (United States)

    Bi, Yi; Liu, Xian-Xuan; Zhang, Heng-Yuan; Yang, Xiao; Liu, Ze-Yun; Lu, Jing; Lewis, Peter John; Wang, Chong-Zhi; Xu, Jin-Yi; Meng, Qing-Guo; Ma, Cong; Yuan, Chun-Su

    2017-04-07

    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 antibacterial activity at much lower concentrations with reduced toxicity.

  18. Design, synthesis and biological evaluation of novel coumarin thiazole derivatives as α-glucosidase inhibitors.

    Science.gov (United States)

    Wang, Guangcheng; He, Dianxiong; Li, Xin; Li, Juan; Peng, Zhiyun

    2016-04-01

    A new series of coumarin thiazole derivatives 7a-7t were synthesized, characterized by (1)H NMR, (13)C NMR and element analysis, evaluated for their α-glucosidase inhibitory activity. The majority of the screened compounds displayed potent inhibitory activities with IC50 values in the range of 6.24±0.07-81.69±0.39μM, when compared to the standard acarbose (IC50=43.26±0.19μM). Structure-activity relationship (SAR) studies suggest that the pattern of substitution in the phenyl ring is closely related to the biological activity of this class of compounds. Among all the tested molecules, compound 7e (IC50=6.24±0.07μM) was found to be the most active compound in the library of coumarin thiazole derivatives. Enzyme kinetic studies showed that compound 7e is a non-competitive inhibitor with a Ki of 6.86μM. Furthermore, the binding interactions of compound 7e with the active site of α-glucosidase were confirmed through molecular docking. This study has identified a new class of potent α-glucosidase inhibitors for further investigation.

  19. Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity.

    Science.gov (United States)

    Mantu, Dorina; Antoci, Vasilichia; Moldoveanu, Costel; Zbancioc, Gheorghita; Mangalagiu, Ionel I

    2016-01-01

    The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed.

  20. Evaluation and optimization of chitosan derivatives-based gene delivery system via kidney epithelial cells

    Directory of Open Access Journals (Sweden)

    S. Safari

    2012-06-01

    Full Text Available Purpose: Non-viral vectors have been widely proposed as safer alternatives to viral vectors, and cationic polymers have gained increasing attention because they can form self-assembly with DNA. Chitosan is also considered to be a good candidate for gene delivery systems, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low solubility and transfection efficiency need to be overcome prior to clinical trial. In this work, we focus on alkyl modified chitosan which might be useful in DNA condensing and efficient gene delivery. Methods: N, N- Diethyl N- Methyl (DEMC and N- Triethyl Chitosan (TEC were synthesized from chitosan polymer. In order to optimize the polymers for gene delivery, we used FITC-dextran (FD. Then the optimized polymer concentrations were used for gene delivery. Fluorescent microscope was used, in order to evaluate the polymers’ efficiency for gene delivery to human embryonic kidney epithelial cells (HEK 293T. Results: This modification increased chitosan’s positive charge, thus these chitosan derivatives spontaneously formed complexes with FD, green fluorescence protein plasmid DNA (pEGFP, red fluorescence protein plasmid DNA (pJred and fluorescent labeled miRNA. Results gained from fluorescent microscope showed that TEC and DEMC were able to transfer FD, DNA and miRNA (micro RNA to HEK cell line. Conclusion: We conclude that these chitosan derivatives present suitable characteristics to be used as non-viral gene delivery vectors to epithelial cells.

  1. 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.

  2. Synthesis, biological evaluation and molecular docking studies of chromone hydrazone derivatives as α-glucosidase inhibitors.

    Science.gov (United States)

    Wang, Guangcheng; Chen, Ming; Wang, Jing; Peng, Yaping; Li, Luyao; Xie, ZhenZhen; Deng, Bing; Chen, Shan; Li, Wenbiao

    2017-07-01

    A series of chromone hydrazone derivatives 4a-4p have been synthesized, characterized by (1)H NMR and (13)C NMR and evaluated for theirinvitro α-glucosidase inhibitory activity. Out of these tested compounds, six (4a, 4b, 4d, 4j, 4o and 4p) displayed potent α-glucosidase inhibitory activity with IC50 values in the range of 20.1±0.19μM to 45.7±0.23μM, as compared to the standard drug acarbose (IC50=817.38±6.27μM). Among this series, compound 4d (IC50=20.1±0.19μM) with 4-sulfonamide substitution at phenyl part of hydrazide was found to be the most active compound. Lineweaver-Burk plot analysis indicated that compound 4d is a non-competitive inhibitor of α-glucosidase. The binding interactions of the most active analogs were confirmed through molecular docking studies. Docking studies showed 4d are interacting with the residues Glu-276, Asp-214, Asp-349 and Arg-439 through hydrogen bonds, arene-anion and arene-cation interactions. In summary, our studies shown that these chromone hydrazone derivatives are a new class of α-glucosidase inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Synthesis and Evaluation of Aminothiazole-Paeonol Derivatives as Potential Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Chia-Ying Tsai

    2016-01-01

    Full Text Available In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using 1H-NMR, 13C-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results indicated that these compounds possess high anticancer potential regarding human gastric adenocarcinoma (AGS cells and human colorectal adenocarcinoma (HT-29 cells. Among these compounds, N-[4-(2-hydroxy-4-methoxyphenylthiazol-2-yl]-4-methoxybenzenesulfonamide (13c had the most potent inhibitory activity, with IC50 values of 4.0 µM to AGS, 4.4 µM to HT-29 cells and 5.8 µM to HeLa cells. The 4-fluoro-N-[4-(2-hydroxy-4-methoxyphenylthiazol-2-yl]benzenesulfonamide (13d was the second potent compound, showing IC50 values of 7.2, 11.2 and 13.8 µM to AGS , HT-29 and HeLa cells, respectively. These compounds are superior to 5-fluorouracil (5-FU for relatively higher potency against AGS and HT-29 human cancer cell lines along with lower cytotoxicity to fibroblasts. Novel aminothiazole-paeonol derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating gastrointestinal adenocarcinoma.

  4. Synthesis, characterization and in vitro anticancer evaluations of two novel derivatives of deferasirox iron chelator.

    Science.gov (United States)

    Salehi, Samie; Saljooghi, Amir Sh; Shiri, Ali

    2016-06-15

    Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator-metal complexes have shifted significant attention to their application in cancer chemotherapy. The present study investigates the new role of deferasirox as an anticancer agent due to its ability to chelate with iron. Because of aminoacids antioxidant effect, deferasirox and its two novel amino acid derivatives have been synthesized through the treatment of deferasirox with DCC as well as glycine or phenylalanine methyl ester. All new compounds have been characterized by elemental analysis, FT-IR NMR and mass spectrometry. Therefore, the cytotoxicity of these compounds was screened for antitumor activity against some cell lines using cisplatin as a comparative standard by MTT assay and Flow cytometry. The impact of iron in the intracellular generation of reactive oxygen species was assessed on HT29 and MDA-MB-231 cells. The potential of the synthesized iron chelators for their efficacy to protect cells against model oxidative injury induced was compared. The reactive oxygen species intracellular fluorescence intensity were measured and the result showed that the reactive oxygen species intensity after iron incubation increased while after chelators incubation the reactive oxygen species intensity were decreased significantly. Besides, the effect of the synthesized compounds on mouse fibroblast cell line (L929) was simultaneously evaluated as control. The pharmacological results showed that deferasirox and its two novel aminoacid derivatives were potent anticancer agents.

  5. 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.

  6. Novel pyrrole derivatives bearing sulfonamide groups: Synthesis in vitro cytotoxicity evaluation, molecular docking and DFT study

    Science.gov (United States)

    Bavadi, Masoumeh; Niknam, Khodabakhsh; Shahraki, Omolbanin

    2017-10-01

    The synthesis of new derivatives of pyrrole substituted sulfonamide groups is described. The in vitro anticancer activity of these pyrroles was evaluated against MCF7, MOLT-4 and HL-60 cells using MTT assay. The target compounds showed inhibitory activity against tested cell lines. Among the compounds, compound 1a exhibited good cytotoxic activity. The potential of this analog to induce apoptosis was confirmed in a nuclear morphological assay by Hoechst 33258 staining in the PC-12 cells. Finally, molecular docking was performed to determine the probable binding mode of the designed pyrrole derivatives into the active site of FGFR1 protein. DFT calculations were carried out at the B3LYP levels of theory with 6-31+G (d,p) basis set for compound 1a. The point group (C1) of it was obtained based on the optimized structures; the calculation of the FT-IR vibrational frequencies, 1H NMR and 13C NMR chemical shifts of the compound were carried out and compared with those obtained experimentally.

  7. Synthesis and Evaluation of 125I Labeled Chalcone Derivatives Containing Bithiophene Moiety as Potential Aβ Probes

    Directory of Open Access Journals (Sweden)

    PENG Cheng

    2015-11-01

    Full Text Available In continuation of the investigation on the bithiophene structure as potential Aβ probes, two halogenated chalcone derivatives containing bithiophene moiety were designed and evaluated as imaging probes for Aβ plaques. In vitro fluorescence staining indicated that they could stain Aβ plaques in the brain sections of AD model mice specifically, in vitro binding assay further confirmed that they displayed high binding affinities to Aβ aggregates (Ki=2.33 nM and 0.88 nM. One radio-iodinated probe, 125I labeleled chalcone derivatives was obtained via iododestannylation reaction with high radiochemical yield and purity (>99%. Moreover, the 125I-labeling compound displayed specific labeling of Aβ plaques in the brain sections of AD model mice with low background, and the specific labeling could be confirmed by thioflavin-S staining. In vivo biodistribution in normal mice indicated that the 125I labeling compound exhibited low initial brain uptake (1.19%ID/g at 2 min and rapid clearance. These preliminary results suggest that 125I labeling compound may serve as novel Aβ imaging probe, although further modifications are needed to improve initial brain uptake.

  8. Synthesis and Biological Evaluation of Lipophilic 1,4-Naphthoquinone Derivatives against Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Shao-Hung Wang

    2015-06-01

    Full Text Available To examine the effect of hydrophobicity on the anticancer activity of 1,4-naphthoquinone derivatives, a series of compounds bearing a 2-O-alkyl-, 3-C-alkyl- or 2/3-N-morpholinoalkyl group were synthesized and evaluated for their anticancer activity against five human cancer cell lines in vitro. The cytotoxicity of these derivatives was assayed against HT-29, SW480, HepG2, MCF-7 and HL-60 cells by the MTT assay. Among them, 2-hydroxy-3-farnesyl-1,4-naphthoquinone (11a was found to be the most cytotoxic against these cell lines. Our results showed that the effectiveness of compound 11a may be attributed to its suppression of the survival of HT-29. Secondly, in the Hoechst 33258 staining test, compound 11a-treated cells exhibited nuclear condensation typical of apoptosis. Additionally, cell cycle analysis by flow cytometry indicated that compound 11a arrested HT-29 cells in the S phase. Furthermore, cell death detected by Annexin V-FITC/propidium iodide staining showed that compound 11a efficiently induced apoptosis of HT-29 in a concentration-dependent manner. Taken together, compound 11a effectively inhibits colon cancer cell proliferation and may be a potent anticancer agent.

  9. Fluorinated betulinic acid derivatives and evaluation of their anti-HIV activity.

    Science.gov (United States)

    Li, Jizhen; Goto, Masuo; Yang, Xiaoming; Morris-Natschke, Susan L; Huang, Li; Chen, Chin-Ho; Lee, Kuo-Hsiung

    2016-01-01

    Several fluorinated derivatives of the anti-HIV maturation agent bevirimat (1) were synthesized and evaluated for anti-HIV replication activity. The modified positions were the C-2, C-3, C-28, and C-30 positions, either directly on the betulinic acid (2) skeleton or in the attached side chains. Compound 18, which has a trifluoromethyl group added to C-30 of its isopropenyl group, exhibited similar potency to 1 against HIV-1NL4-3. In total, our current studies support our prior conclusion that C-30 allylic modification is unlikely to be a pharmacophore for anti-HIV activity, but could be a meaningful route to manipulate other properties of 2-related compounds.

  10. A method for evaluating models that use galaxy rotation curves to derive the density profiles

    CERN Document Server

    de Almeida, Álefe O F; Rodrigues, Davi C

    2016-01-01

    There are some approaches, either based on General Relativity (GR) or modified gravity, that use galaxy rotation curves to derive the matter density of the corresponding galaxy, and this procedure would either indicate a partial or a complete elimination of dark matter in galaxies. Here we review these approaches, clarify the difficulties on this inverted procedure, present a method for evaluating them, and use it to test two specific approaches that are based on GR: the Cooperstock-Tieu (CT) and the Balasin-Grumiller (BG) approaches. Using this new method, we find that neither of the tested approaches can satisfactorily fit the observational data without dark matter. The CT approach results can be significantly improved if some dark matter is considered, while for the BG approach no usual dark matter halo can improve its results.

  11. In vitro evaluation of anticancer effect and neurotoxicity of Styrylpyrone derivative (SPD)

    Science.gov (United States)

    Yip, Chee-Wai; Nagaoka, Yasuo; Nor, Norefrina Shafinaz Md.; Ibrahim, Nazlina

    2016-11-01

    The increasing number of death due to cancer emphasizes the need of novel anticancer agents. Styrylpyrone derivative (SPD) was previously found to have potential anticancer action towards many types of cancer. Some of the SPD-anticancer mechanisms were elucidated as induction of cancer cell apoptosis. However, more understanding on cancer cell type specific action of SPD-anticancer effects needs to be evaluated. HCT-116 cell line, a type of human colon carcinoma, was used to study SPD-anticancer effect. It was found that SPD concentration as low as 0.25 µM was able to inhibit 80% growth of cancer cells. IC50 value of SPD for HCT-116 was found to be 0.038 µM. Neurotoxicity test, carried out to determine the adverse effect of SPD towards nerve cells, gives CC50 value as 4.88 µM, thus concluded it to be a neurotoxic compound.

  12. Synthesis, characterization and evaluation of antioxidant and anticancer activities of novel benzisoxazole-substituted-allyl derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Anand, Mohanam [Kingston Engineering College, Vellore (India); Selvaraj, Vaithialingam [University College of Engineering-Villupuram, Villupuram (India); Alagar, Muthukaruppan [Anna University, Chennai (India)

    2014-04-15

    A novel series of various 2-allylbenzo[d]isoxazol-3(2H)-ones were synthesized using benzo[d]isoxazol-3(2H)-one treated with different allyl bromides/chlorides in the presence of water-mediated cesium carbonate as a new catalyst 3(a-h). The structures of the newly synthesized Benzisoxazole-substituted-allyl derivatives were characterized by spectroscopic methods and mass spectrometry. These synthesized compounds were evaluated for their in vitro antioxidant and anticancer activity. Compounds 3b, d, f, h were identified as the best hit against HT-29 Human colon cancer cells. Similarly, compounds like 3b, d, f, h showed significant antioxidant activity compared to the standard drug butylated hydroxy toluene (BHT)

  13. A method for evaluating models that use galaxy rotation curves to derive the density profiles

    Science.gov (United States)

    de Almeida, Álefe O. F.; Piattella, Oliver F.; Rodrigues, Davi C.

    2016-11-01

    There are some approaches, either based on General Relativity (GR) or modified gravity, that use galaxy rotation curves to derive the matter density of the corresponding galaxy, and this procedure would either indicate a partial or a complete elimination of dark matter in galaxies. Here we review these approaches, clarify the difficulties on this inverted procedure, present a method for evaluating them, and use it to test two specific approaches that are based on GR: the Cooperstock-Tieu (CT) and the Balasin-Grumiller (BG) approaches. Using this new method, we find that neither of the tested approaches can satisfactorily fit the observational data without dark matter. The CT approach results can be significantly improved if some dark matter is considered, while for the BG approach no usual dark matter halo can improve its results.

  14. Synthesis and evaluation of radiolabeled piperazine derivatives of vesamicol as SPECT agents for cholinergic neurons

    Energy Technology Data Exchange (ETDEWEB)

    Bando, Kazunori E-mail: bkazunori@drl.co.jp; Taguchi, Kazumi; Ginoza, Yasushi; Naganuma, Tomoyoshi; Tanaka, Yoshitomo; Koike, Katsuo; Takatoku, Keizo

    2001-04-01

    To diagnose and investigate neurodegenerative diseases affecting cholinergic neuron density, piperazine derivatives of vesamicol were synthesized and evaluated. Previously, we reported that trans-5-iodo-2-hydroxy-3-[4-phenylpiperazinyl] tetralin (DRC140, 1) possessed high selectivity for vesicular acetylcholine transporter (VAChT). In present study of the effect of alkyl substituents, we observed that the introduction of a methyl group into the ortho or meta positions of the phenyl group of 1 increased affinity for VAChT. trans-5-Iodo-2-hydroxy-3-[4-[2-methylphenyl] piperazinyl]tetralin (2) displayed high affinity and specificity for VAChT. The regional distributions of radioactivity in the rat brain correlated well with known patterns of central cholinergic innervation. [{sup 123}I]2 is a potentially useful compound for SPECT imaging.

  15. Synthesis and biological evaluation of nitric oxide-releasing sixalkoxyl biphenyl derivatives as anticancer agents

    Institute of Scientific and Technical Information of China (English)

    Xiang Wen Kong; Yi Hua Zhang; Li Dai; Hui Ji; Yi Sheng Lai; Si Xun Peng

    2008-01-01

    A series of novel nitric oxide-donating sixalkoxyl biphenyl derivatives (14a-i)were synthesized by coupling furoxan with alkoxyl biphenyl skeleton using amino acids as the spacers,and their cytotoxicity against HepG2 cells in vitro were evaluated by MTr method.It was found that 14c,14d,14f,14i,14j and 14k showed more potent cytotoxic activities than control 5-fluorouracil.NO release assay of target compounds indicated that the maximum amount of NO released by most active compounds 14c and 14j was about 6 x 10-2μmol/L,whereas 14a and 14h with very weak activity only released NO of 1 x 10-μmol/L.

  16. Synthesis and Evaluation of Substituted Chroman-4-one and Chromone Derivatives as Sirtuin 2-Selective Inhibitors

    Science.gov (United States)

    2012-01-01

    A series of substituted chromone/chroman-4-one derivatives has been synthesized and evaluated as novel inhibitors of SIRT2, an enzyme involved in aging-related diseases, e.g., neurodegenerative disorders. The analogues were efficiently synthesized in a one-step procedure including a base-mediated aldol condensation using microwave irradiation. The most potent compounds, with inhibitory concentrations in the low micromolar range, were substituted in the 2-, 6-, and 8-positions. Larger, electron-withdrawing substituents in the 6- and 8-positions were favorable. The most potent inhibitor of SIRT2 was 6,8-dibromo-2-pentylchroman-4-one with an IC50 of 1.5 μM. The synthesized compounds show high selectivity toward SIRT2 over SIRT1 and SIRT3 and represent an important starting point for the development of novel SIRT2 inhibitors. PMID:22746324

  17. Synthesis and biological evaluation of sophocarpinic acid derivatives as anti-HCV agents

    Directory of Open Access Journals (Sweden)

    Yinghong Li

    2014-08-01

    Full Text Available Chronic hepatitis C virus (HCV infection has become a major public health burden worldwide. Twenty-two sophocarpinic acid or matrine derivatives were synthesized and their anti-HCV activities were evaluated in vitro. The structure-activity analysis revealed that (i sophocarpinic acids with a D-seco 3-ring structure scaffold were more favorable than matrines with a 4-ring scaffold; (ii the introduction of an electron-withdrawing group on the phenyl ring in 12-N-benzenesulfonyl Δβγ sophocarpinic acids was beneficial for the antiviral activity against HCV. Among them, compounds 9h and 9j exhibited the most potent inhibitory activities on HCV replication with selectivity indies of 70.3 and 30.9, respectively. Therefore, both were selected as antiviral candidates for further investigation.

  18. Derivation and evaluation of the fourth moment of NMR lineshape in zero-field.

    Science.gov (United States)

    Cutsuridis, Vassilis; Kahol, Pawan K

    2008-10-01

    An expression for the fourth moment in zero-field NMR has been analytically derived and numerically evaluated for a rigid cubic lattice. Model simulations have been performed to calculate the second moment, the fourth moment, the ratio of the fourth moment to the square of the second moment, and the width of the resonance line for a crystal and a polycrystalline material in high-field as well as in zero-field NMR. The simulation results allow us to draw two conclusions: (1) zero-field NMR gives sharper and better defined spectra than the high-field NMR and (2) the ratio of the high- to zero-field resonance line-widths is 4 for a crystal, whereas it is 11 for a polycrystalline material.

  19. [Synthesis and biological evaluation of 2-(3-butynoicamidophenyl) benzothiazole derivatives as antitumor agents].

    Science.gov (United States)

    Yin, Gui-Lin; Li, Yan; Tang, Ke; Jin, Xiao-Feng; Chen, Xiao-Guang; Li, Li; Feng, Zhi-Qiang

    2014-06-01

    A series of 2-(3-butynoicamidophenyl)benzothiazole derivatives were synthesized starting from 4-fluoro-3-nitrobenzoic acid. Structures of all the synthesized compounds were confirmed by 1H NMR and HR-MS. Their antitumor activities against human tumor cells lines (HCT116, Mia-PaCa2, U87-MG, A549, NCI-H1975) were evaluated by MTT assay. The results revealed that most of the synthesized compounds showed potent activities against HCT116, Mia-PaCa2, U87-MG tumor cells lines. Particularly, compounds 14c and 14h exhibited better activity with IC50 values of 1 x 10(-8) mol x L(-1) against U87-MG and HCT116 respectively. The structure-activity relationship of compounds was also discussed preliminarily.

  20. Synthesis of Some Pyrazolone Derivatives and Evaluation of its Antibacterial and Cytotoxic Activity

    Directory of Open Access Journals (Sweden)

    Rishiram Prajuli

    2015-12-01

    Full Text Available A series of novel pyrazolone derivative were synthesized by two different schemes (scheme-1 by the reaction of phenyl hydrazine and ethyl acetoacetate with substituted benzaldehydes PYR-1 to PYR-4 and (by the reaction of synthesized chalcone with phenyl hydrazine PYR-5 and characterised with its physical parameters (M.P, colour, %yield, solubility etc.. The entire synthesized compound was tested for their antimicrobial activity against Gram-positive and Gram-negative strains of bacteria and brimeshrimp bioassay was conducted for evaluation of cytotoxic activity The Investigation of antimicrobial screening data revealed that most of the tested compounds showed moderate to good antimicrobial activity. And cytotoxicity activity of compounds was also found to be satisfactory.

  1. Schisanhenol derivatives and their biological evaluation against tobacco mosaic virus (TMV).

    Science.gov (United States)

    Wang, Qing-Yao; Deng, Lu-Lu; Liu, Jia-Ju; Zhang, Jian-Xin; Hao, Xiao-Jiang; Mu, Shu-Zhen

    2015-03-01

    Schisanhenol (Sol) was isolated from Schisandra rubriflora, and a series of derivatives (1-16, 15a-16a, and 15b-16b) were designed and prepared by chemical modification. The curative and protective effects of these dibenzocyclooctadiene lignan analogues against tobacco mosaic virus (TMV) were evaluated. Most analogues exhibited stronger protective effects than the positive control ningnanmycin. Dibromoschisanhenol (6) at 0.25mM exhibited the strongest protective activity (83.5±1.8% at 0.25mM), and 14-(3, 5-dibenzyloxy)-benzoyloxyschisanhenol (16) showed a significant curative effect (78.0±3.8% at 0.15mM) that was much stronger than that of the commercial virucide ningnanmycin. This study is the first to demonstrate that natural dibenzocyclooctadiene lignans and analogues are active against plant viruses. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Synthesis and Biological Evaluation of Mannich Bases of Isoxazoline Derivatives as Novel Anti-Microbial Agents

    Directory of Open Access Journals (Sweden)

    Pawar Sudhir

    2012-01-01

    Full Text Available A novel series of compounds were synthesized by condensation reaction of substituted acetophenone (1a-b with substituted aldehyde (2a-b in presence of alcoholic sodium hydroxide to get intermediate chalcones (3a-c, which were further treated with hydroxylamine hydrochloride in presence of sodium hydroxide to get isoxazolines derivatives (4a-c. The latter were refluxed with substituted primary amines and formaldehyde for 6-10 h to afford Mannich bases. The synthesized compounds were characterized on the basis of their spectral (IR, 1HNMR data and evaluated for the antimicrobial activity by using Zone of Inhibition by cup plate method and Minimum Inhibitory Concentration by broth dilution method.

  3. Evaluation of cationic micropeptides derived from the innate immune system as inhibitors of marine biofouling.

    Science.gov (United States)

    Trepos, Rozenn; Cervin, Gunnar; Pile, Claire; Pavia, Henrik; Hellio, Claire; Svenson, Johan

    2015-01-01

    A series of 13 short synthetic amphiphilic cationic micropeptides, derived from the antimicrobial iron-binding innate defence protein lactoferrin, have been evaluated for their capacity to inhibit the marine fouling process. The whole biofouling process was studied and microfouling organisms such as marine bacteria and microalgae were included as well as the macrofouling barnacle Balanus improvisus. In total 19 different marine fouling organisms (18 microfoulers and one macrofouler) were included and both the adhesion and growth of the microfoulers were investigated. It was shown that the majority of the peptides inhibited barnacle cyprid settlement via a reversible nontoxic mechanism, with IC50 values as low as 0.5 μg ml(-1). Six peptides inhibited adhesion and growth of microorganisms. Two of these were particularly active against the microfoulers with MIC-values ranging between 0.01 and 1 μg ml(-1), which is comparable with the commercial reference antifoulant SeaNine.

  4. 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

  5. A new approach to synthesis of benzyl cinnamate: Optimization by response surface methodology.

    Science.gov (United States)

    Zhang, Dong-Hao; Zhang, Jiang-Yan; Che, Wen-Cai; Wang, Yun

    2016-09-01

    In this work, the new approach to synthesis of benzyl cinnamate by enzymatic esterification of cinnamic acid with benzyl alcohol is optimized by response surface methodology. The effects of various reaction conditions, including temperature, enzyme loading, substrate molar ratio of benzyl alcohol to cinnamic acid, and reaction time, are investigated. A 5-level-4-factor central composite design is employed to search for the optimal yield of benzyl cinnamate. A quadratic polynomial regression model is used to analyze the experimental data at a 95% confidence level (P<0.05). The coefficient of determination of this model is found to be 0.9851. Three sets of optimum reaction conditions are established, and the verified experimental trials are performed for validating the optimum points. Under the optimum conditions (40°C, 31mg/mL enzyme loading, 2.6:1 molar ratio, 27h), the yield reaches 97.7%, which provides an efficient processes for industrial production of benzyl cinnamate.

  6. Molecular Interaction Studies of Benzyl Alcohols with Methacrylates in Carbon Tetrachloride using Frequency Domain Technique

    Directory of Open Access Journals (Sweden)

    S. Radhakrishnan

    2016-08-01

    Full Text Available The dielectric relaxation of benzyl alcohol substitutents (benzyl alcohol, m-methylbenzyl alcohol and m-nitrobenzyl alcohol with methyl methacrylate and butyl methacrylate in dilute solution of carbon tetrachloride is measured at 9.37 GHz using Frequency domain (X-band technique. Different dielectric parameters like dielectric constant (ε׳, dielectric loss factor (ε״ at Microwave frequency, static dielectric constant (ε0 and dielectric constant at infinite dilution (ε∞ at optical frequency have been determined. From the measured dielectric data, the relaxation time (t calculated using Higasi method and activation energies (∆Ft and ∆Fη have been determined. All the dielectric parameters that are vary with the substitutent change in benzyl alcohol andchain length of acrylic esters. Suggests that, the proton donating ability is varying with the substitution of benzyl alcohol and proton accepting ability is varying with the chain length of acrylic esters. The relaxation time and molar free energy activation of 1:1 molar ratio is greater than other higher molar ratios (i.e. 3:1, 2:1, 1:2, 1:3 confirm that the existence of most likely 1:1 complex formation between the studied systems and also complex formation formed between free hydroxyl group of substituted benzyl alcohols and carbonyl group of acrylic esters (MMA and EMA.

  7. 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

  8. Marinopyrrole derivatives with sulfide spacers as selective disruptors of Mcl-1 binding to pro-apoptotic protein Bim.

    Science.gov (United States)

    Cheng, Chunwei; Liu, Yan; Balasis, Maria E; Garner, Thomas P; Li, Jerry; Simmons, Nicholas L; Berndt, Norbert; Song, Hao; Pan, Lili; Qin, Yong; Nicolaou, K C; Gavathiotis, Evripidis; Sebti, Said M; Li, Rongshi

    2014-07-29

    A series of novel marinopyrroles with sulfide and sulphone spacers were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-xL, was evaluated using ELISA assays. Fluorescence-quenching (FQ) assays confirmed the direct binding of marinopyrroles to Mcl-1. Benzyl- and benzyl methoxy-containing sulfide derivatives 4 and 5 were highly potent dual Mcl-1/Bim and Bcl-xL/Bim disruptors (IC50 values of 600 and 700 nM), whereas carboxylate-containing sulfide derivative 9 exhibited 16.4-fold more selectivity for disrupting Mcl-1/Bim over Bcl-xL/Bim binding. In addition, a nonsymmetrical marinopyrrole 12 is as equally potent as the parent marinopyrrole A (1) for disrupting both Mcl-1/Bim and Bcl-xL/Bim binding. Some of the derivatives were also active in intact human breast cancer cells where they reduced the levels of Mcl-1, induced programd cell death (apoptosis) and inhibited cell proliferation.

  9. Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim

    Directory of Open Access Journals (Sweden)

    Chunwei Cheng

    2014-07-01

    Full Text Available A series of novel marinopyrroles with sulfide and sulphone spacers were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-xL, was evaluated using ELISA assays. Fluorescence-quenching (FQ assays confirmed the direct binding of marinopyrroles to Mcl-1. Benzyl- and benzyl methoxy-containing sulfide derivatives 4 and 5 were highly potent dual Mcl-1/Bim and Bcl-xL/Bim disruptors (IC50 values of 600 and 700 nM, whereas carboxylate-containing sulfide derivative 9 exhibited 16.4-fold more selectivity for disrupting Mcl-1/Bim over Bcl-xL/Bim binding. In addition, a nonsymmetrical marinopyrrole 12 is as equally potent as the parent marinopyrrole A (1 for disrupting both Mcl-1/Bim and Bcl-xL/Bim binding. Some of the derivatives were also active in intact human breast cancer cells where they reduced the levels of Mcl-1, induced programd cell death (apoptosis and inhibited cell proliferation.

  10. Synthesis of new quinoxaline-2-carboxylate 1,4-dioxide derivatives as anti-Mycobacterium tuberculosis agents.

    Science.gov (United States)

    Jaso, Andrés; Zarranz, Belén; Aldana, Ignacio; Monge, Antonio

    2005-03-24

    Twenty-nine new 6(7)-substituted quinoxaline-2-carboxylate 1,4-dioxide derivatives were synthesized and evaluated for in vitro antituberculosis activity. In general, the in vitro activity is significantly affected by substituents on the quinoxaline nucleus. It has been observed that the presence of a chloro, methyl, or methoxy group in position 7 of the benzene moiety reduces the MIC and IC(50) values. However, antituberculosis activity principally depends on the substituents in the carboxylate group, improving in the following order: benzyl > ethyl > 2-methoxyethyl > allyl > tert-butyl. Fourteen compounds have been selected for macrophage assay, and the results show that ethyl and benzyl 3-methylquinoxaline-2-carboxylate 1,4-dioxide derivatives with the chlorine group in position 7 of the benzene moiety (compounds 10 and 26) and the unsubstituted derivatives (compounds 11 and 27) have good antitubercular activity, including activity in macrophages. In addition, compounds 7 and 28 (the only ones tested up to now) are active against drug-resistant strains of M. tuberculosis H(37)Rv. In conclusion, the potency, selectivity, and low cytotoxicity of these compounds make them valid leads for synthesizing new compounds that possess better activity.

  11. 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.

  12. Synthesis and preliminary evaluation of 2-arylhydroxyquinoline derivatives for tau imaging.

    Science.gov (United States)

    Tago, Tetsuro; Furumoto, Shozo; Okamura, Nobuyuki; Harada, Ryuichi; Ishikawa, Yoichi; Arai, Hiroyuki; Yanai, Kazuhiko; Iwata, Ren; Kudo, Yukitsuka

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia. Senile plaques, consisting of β-amyloid, and neurofibrillary tangles (NFTs), composed of tau protein, are representative pathological hallmarks of AD. It is believed that the accumulation of NFTs precedes the onset of clinical symptoms of AD and correlates with the progression of memory dysfunction. Thus, the use of noninvasive detection techniques including radiolabeled probes and positron emission tomography (PET) will facilitate early diagnosis or staging of AD. In this study, we synthesized and evaluated novel hydroxylated 2-arylquinoline derivatives as tau imaging PET probes. The binding affinities of compounds for tau were evaluated by fluorescent staining of the AD hippocampal section and a competitive binding assay using [(18) F]THK-523. THK-951 showed high binding affinity for tau pathology in an AD brain section and K18Δ280K fibrils (Ki  = 20.7 nM); thus, we radiosynthesized a (11) C-labeled THK-951 and further studied its potential as a tau PET probe. The [(11) C]THK-951 demonstrated excellent kinetics in a normal mouse brain (3.23% ID/g at 2 min postinjection and 0.15% ID/g at 30 min postinjection) and showed the labeling of NFTs in an AD brain section by autoradiography assay. These findings indicate the availability of [(11) C]THK-951 for in vivo PET imaging of tau pathology in AD. Copyright © 2013 John Wiley & Sons, Ltd.

  13. 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.

  14. Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents

    Directory of Open Access Journals (Sweden)

    Mehlika Dilek Altıntop

    2016-11-01

    Full Text Available New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl-1-([1,1′-biphenyl]-4-ylmethylenethiosemicarbazide (5 was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells. Compound 5 increased early and late apoptosis in A549 and C6 cells. Compound 5 also caused disturbance on mitochondrial membrane potential and showed DNA synthesis inhibitory activity in A549 and C6 cells. Compound 5 was investigated for SIRT1 inhibitory activity to provide mechanistic insight and for that purpose docking studies were also performed for this compound on SIRT1. On the other hand, compound 5 did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between anticancer activity of compound 5 and cholinesterases.

  15. Evaluation of Doubled Haploid Derivatives of the Flue-cured Nicotianatabacum cv. Wislica

    Directory of Open Access Journals (Sweden)

    Berbec A

    2014-12-01

    Full Text Available A total of 51 doubled haploid (DH derivatives of the flue-cured true-breeding tobacco variety Wislica were obtained via anther culture and colchicine-induced chromosome doubling. Of that number eight DH lines showed morphological aberrations and/or reduced vigour that made them unfit to be grown in the field. The remaining 43 DH lines were grown in 2001 under regular flue-cured tobacco management and evaluated for principal growth indicators, yield, curability and gross money returns from unit area. In 2002, the evaluation was scaled down to include 13 best performing DH lines of 2001. The DH lines showed a considerable variation for basic growth parameters. Usually, the DH lines had more leaves but were shorter than the parental genotype mostly due to shorter internodes. The majority of DH lines showed delayed flowering compared to the parental cultivar. Yields of cured leaves varied extensively, some of the DH lines yielding above and some below cv. Wislica. Curability measured as percentage of light (1st to 3rd grades was generally lower in DH lines compared to that in cv. Wislica. However, because of the high leaf yield some of the DH lines were not inferior to the parental cultivar with respect to money returns from unit area.

  16. Polymer-clay nanocomposites obtained by solution polymerization of vinyl benzyl triammonium chloride in the presence of advanced functionalized clay

    Indian Academy of Sciences (India)

    Raluca Ianchis; Dan Donescu; Ludmila Otilia Cinteza; Violeta Purcar; Cristina Lavinia Nistor; Critian Petcu; Cristian Andi Nicolae; Raluca Gabor; Silviu Preda

    2014-05-01

    Polymer-clay nanocomposites were synthesized by solution polymerization method using advanced functionalized clay and vinyl benzyl trimethyl ammonium chloride as monomer. First stage consisted in the silylation of a commercial organo-modified clay-Cl 20A using alkoxysilanes with different chain lengths. In the second step, the synthesis and characterization of polymer-nanocomposites were followed. To evaluate the clay functionalization process as well as the final polymer-clay products, thermogravimetric,X-ray diffraction, dynamic light scattering, Fourier transform infrared spectroscopy and three test liquid contact angles analyses were used. The loss of ammonium ions from commercial clay, the grafting degree, the lengths and the nature of alkyl chain influence the dispersion of the advanced modified clay into the polymer solution and, furthermore, the properties of the final polymer-clay nanocomposite film.

  17. Synthesis and tunability of highly electron-accepting, N-benzylated "phosphaviologens".

    Science.gov (United States)

    Stolar, Monika; Borau-Garcia, Javier; Toonen, Mark; Baumgartner, Thomas

    2015-03-11

    We report a structure-property study on phosphoryl-bridged viologen analogues with a remarkably low reduction threshold. Utilizing different benzyl groups for N-quaternization, we were able to confirm the p-benzyl substituent effect on the electronic tunability of the system while maintaining the characteristic chromic response of viologens with two fully reversible one-electron reductions. Due to the considerably increased electron-acceptor properties of the phosphoryl-bridged bipyridine precursor, N-benzylation was found to be very challenging and required the development of new synthetic strategies toward the target viologen species. This study also introduces a new and convenient way for the anion exchange of viologen systems by utilizing methyl triflate. Finally, the practical utility of the new species was verified in simplified proof-of-concept electrochromic devices.

  18. Oxidation of benzyl alcohol by K2FeO4 to benzaldehyde over zeolites

    Science.gov (United States)

    Wang, Yuan-Yuan; Song, Hua; Song, Hua-Lin; Jin, Zai-Shun

    2016-10-01

    A novel and green procedure for benzaldehyde synthesis by potassium ferrate oxidation of benzyl alcohol employing zeolite catalysts was studied. The prepared oxidant was characterized by SEM and XRD. The catalytic activity of various solid catalysts was studied using benzyl alcohol as a model compound. USY was found to be a very efficient catalyst for this particular oxidation process. Benzaldehyde yields up to 96.0% could be obtained at the following optimal conditions: 0.2 mL of benzyl alcohol, 4 mmol of K2FeO4, 0.5 g of USY zeolite; 20 mL of cyclohexene, 0.3 mL of acetic acid (36 wt %), 30°C temperature, 4 h reaction time.

  19. Nickel-catalyzed cross-coupling reactions of benzylic zinc reagents with aromatic bromides, chlorides and tosylates.

    Science.gov (United States)

    Schade, Matthias A; Metzger, Albrecht; Hug, Stephan; Knochel, Paul

    2008-07-14

    Benzylic zinc reagents prepared by direct insertion of zinc to benzylic chlorides in the presence of LiCl undergo smooth cross-coupling reactions with aromatic chlorides, bromides and tosylates using Ni(acac)(2) and PPh(3) as a catalyst system.

  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. Therapeutic Agents in Acne Vulgaris: Part II. D-Alpha Amino Benzyl Penicillin, Erythromycin and Sulfadimethoxine.

    Science.gov (United States)

    Stewart, W D; Maddin, S; Nelson, A J; Danto, J L

    1965-06-26

    A total of 379 patients with pustular and cystic acne vulgaris were selected for study in three groups. Each group was assigned one of the following medications: benzyl penicillin, erythromycin, sulfadimethoxine, or placebo; these were to be compared with tetracycline, a medication whose effectiveness was previously demonstrated in this type of acne. The study revealed a larger number of favourable responses to tetracycline and erythromycin than to sulfadimethoxine. Sulfadimethoxine, however, produced a greater number of favourable responses than did the benzyl penicillin or the placebo; the last-named had equivalent results.

  2. Efficient oxidation of benzyl alcohol with heteropolytungstate as reaction-controlled phase-transfer catalyst

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A series of heteropolytungstates has been synthesized and utilized as catalysts to catalyze oxidation of benzyl alcohol with aqueous hydrogen peroxide. The results indicated that three of these catalysts showed the properties of reaction-controlled phasetransfer catalysis, and they had excellent catalytic ability to the oxidation of benzyl alcohol. No other by-products were detected by gas chromatography. Once the hydrogen peroxide was consumed completely, the catalyst precipitated from solvent, and the results of the catalyst recycle showed that the catalyst had high stability.

  3. Catalyst system and process for benzyl ether fragmentation and coal liquefaction

    Science.gov (United States)

    Zoeller, Joseph Robert

    1998-04-28

    Dibenzyl ether can be readily cleaved to form primarily benzaldehyde and toluene as products, along with minor amounts of bibenzyl and benzyl benzoate, in the presence of a catalyst system comprising a Group 6 metal, preferably molybdenum, a salt, and an organic halide. Although useful synthetically for the cleavage of benzyl ethers, this cleavage also represents a key model reaction for the liquefaction of coal; thus this catalyst system and process should be useful in coal liquefaction with the advantage of operating at significantly lower temperatures and pressures.

  4. Aqueous high-temperature chemistry of carbo- and heterocycles. 2. Monosubstituted benzenes: Benzyl alcohol, benzaldehyde, and benzoic acid

    Energy Technology Data Exchange (ETDEWEB)

    Katritzky, A.R.; Balasubramanian, M. (Univ. of Florida, Gainesville (USA)); Siskin, M. (Exxon Research and Engineering Company, Annandale, NJ (USA))

    Benzyl alcohol is not very reactive under aquathermolysis conditions, except in the presence of acids. Almost all the products are formed by ionic pathways. It undergoes reversible dehydration to dibenzyl ether, disproportionation to benzaldehyde and toluene, and self-benzylation to 2- and 4-benzylbenzyl alcohols. These benzylbenzyl alcohols can react further, but major amounts of polyalkylated products are formed by the mono- and dibenzylation of toluene to give a range of dibenzyltoluenes and (benzylbenzyl)toluenes. Small amounts of diphenylmethane and bibenzyl and their benzylated products are also formed. The behavior of benzyl alcohol in the presence of phenol, pyridine, benzaldehyde, and benzene is also studied and rationalized. Benzaldehyde is much less reactive, except in the presence of formaldehyde, and especially in the presence of formic acid, when considerable formation of benzyl alcohol occurs and siphoning into this reaction matrix is observed. Benzoic acid is still less reactive.

  5. Synthesis and Antioxidant Activity of Hydroxytyrosol Alkyl-Carbonate Derivatives.

    Science.gov (United States)

    Fernandez-Pastor, Ignacio; Fernandez-Hernandez, Antonia; Rivas, Francisco; Martinez, Antonio; Garcia-Granados, Andres; Parra, Andres

    2016-07-22

    Three procedures have been investigated for the isolation of tyrosol (1) and hydroxytyrosol (2) from a phenolic extract obtained from the solid residue of olive milling. These three methods, which facilitated the recovery of these phenols, were chemical or enzymatic acetylation, benzylation, and carbomethoxylation, and subsequent carbonylation or acetonation reactions. Several new lipophilic alkyl-carbonate derivatives of hydroxytyrosol have been synthesized, coupling the primary hydroxy group of this phenol, through a carbonate linker, using alcohols with different chain lengths. The antioxidant properties of these lipophilic derivatives have been evaluated by different methods and compared with free hydroxytyrosol (2) and also with the well-known antioxidants BHT and α-tocopherol. Three methods were used for the determination of this antioxidant activity: FRAP and ABTS assays, to test the antioxidant power in hydrophilic media, and the Rancimat test, to evaluate the antioxidant capacity in a lipophilic matrix. These new alkyl-carbonate derivatives of hydroxytyrosol enhanced the antioxidant activity of this natural phenol, with their antioxidant properties also being higher than those of the commercial antioxidants BHT and α-tocopherol. There was no clear influence of the side-chain length on the antioxidant properties of the alkyl-carbonate derivatives of 2, although the best results were achieved mainly by the compounds with a longer chain on the primary hydroxy group of this natural phenolic substance.

  6. Design, synthesis, biological evaluation and preliminary mechanism study of novel benzothiazole derivatives bearing indole-based moiety as potent antitumor agents.

    Science.gov (United States)

    Ma, Junjie; Bao, Guanglong; Wang, Limei; Li, Wanting; Xu, Boxuan; Du, Baoquan; Lv, Jie; Zhai, Xin; Gong, Ping

    2015-01-01

    Through a structure-based molecular hybridization approach, a series of novel benzothiazole derivatives bearing indole-based moiety were designed, synthesized and screened for in vitro antitumor activity against four cancer cell lines (HT29, H460, A549 and MDA-MB-231). Most of them showed moderate to excellent activity against all the tested cell lines. Among them, compounds 20a-w with substituted benzyl-1H-indole moiety showed better selectivity against HT29 cancer cell line than other compounds. Compound 20d exhibited excellent antitumor activity with IC50 values of 0.024, 0.29, 0.84 and 0.88 μM against HT29, H460, A549 and MDA-MB-231, respectively. Further mechanism studies indicated that the marked pharmacological activity of compound 20d might be ascribed to activation of procaspase-3 (apoptosis-inducing) and cell cycle arrest, which had emerged as a lead for further structural modifications. Furthermore, 3D-QSAR model (training set: q(2) = 0.850, r(2) = 0.987, test set: r(2) = 0.811) was built to provide a comprehensive guide for further structural modification and optimization.

  7. Synthesis of novel furobenzopyrone derivatives and evaluation of their antimicrobial and antiinflammatory activity

    Directory of Open Access Journals (Sweden)

    Srinivasan K

    2007-01-01

    Full Text Available Certain 4′-(4′′-substituted phenyl-4-methylfurobenzopyrones were synthesized and evaluated for antibacterial activity. Six of the synthesized compounds were also screened for their antiinflammatory activity. Substituted resorcinols were condensed with ethyl acetoacetate to afford different coumarins (2a-c. Various substituted phenacyl bromides (4a-g were prepared by the bromination of para-substituted acetophenones. The coumarins (2a-c and phenacyl bromides (4a-g were condensed to give oxoethers (5a-s. These were cyclised by using 1 M sodium hydroxide to afford the desired furobenzopyrone derivatives (FCa-s. All the compounds have been evaluated for their antibacterial activity against different strains of gram positive and gram negative bacteria. All the compounds have shown good activity against Pseudomonas aeruginosa . Compounds, 3-(4-chlorophenyl-5-methylfuro-[3,2-g][1]benzopyran-7-one, 3-(4-chlorophenyl-5,9-dimethylfuro[3,2-g][1]benzopyran-7-one and 4,5-dimethyl-3-phenylfuro[3,2-g][1]benzopyran-7-one (FCe, FCi, FCn were active against E. coli . A few compounds showed moderate activity against Bacillus subtilis also. Antiinflammatory activity of six selected compounds was also tested using the carrageenan-induced rat paw oedema method. Among them, 5-methyl-3-p-tolylfuro[3,2-g][1]benzopyran-7-one (FCg showed excellent activity. 5-Methyl-3-phenylfuro[3,2-g][1]benzopyran-7-one (FCa and 4,5-dimethyl-3-(4-nitrophenyl-furo[3,2-g][1]benzopyran-7-one (FCc showed activity comparable to that of the standard drug ibuprofen.

  8. Synthesis and antimicrobial evaluation of L-phenylalanine-derived C5-substituted rhodanine and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone.

    Science.gov (United States)

    Jin, Xin; Zheng, Chang-Ji; Song, Ming-Xia; Wu, Yan; Sun, Liang-Peng; Li, Yin-Jing; Yu, Li-Jun; Piao, Hu-Ri

    2012-10-01

    Four novel series of compounds, including the l-phenylalanine-derived C5-substituted rhodanine (6a-q, 7a-j) and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone (9a-e, 11a-e) have been designed, synthesized, characterized, and evaluated for their antibacterial activity. Some of these compounds showed significant antibacterial activity against Gram-positive bacterias, especially against the strains of multidrug-resistant clinical isolates, among which compounds 6c-e, 6g, 6i, 6j and 6q exhibiting high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentration (MIC) values of 2 μg/mL. Compound 6q showed the most potent activity of all of the compounds against all of the test multidrug-resistant clinical isolates tested. Unfortunately, however, none of the compounds were active against Gram-negative bacteria at 64 μg/mL.

  9. Evaluation of the teratogenic potential and reproductive toxicity of coal-derived naphtha.

    Science.gov (United States)

    McKee, R H; Hinz, J P; Traul, K A

    1986-06-15

    Liquids which are derived from coal liquefaction processes and boil above approximately 250 degrees C have induced terata in rats. However, few studies have addressed the teratogenic potential of coal liquids which boil below 250 degrees C. The present studies evaluated the reproductive and teratogenic potential of EDS hydrotreated naphtha, a refined coal liquid boiling below 177 degrees C. These studies were conducted by inhalation exposures with Sprague-Dawley rats at target vapor concentrations of 0.2, 1.0, and 5.0 g/m3. The first study assessed teratogenesis. There was no evidence that inhalation exposures for 6 hr per day between Days 6 and 19 of gestation induced maternal toxicity, fetal toxicity, or malformation. In a second study, rats were exposed for 6 hr per day, 5 days per week for 13 weeks, and then mated to assess reproductive toxicity. There was little evidence that inhalation exposure to EDS hydrotreated naphtha adversely affected reproductive performance or fetal development in Sprague-Dawley rats. A low incidence of malformations was observed in treated groups, but these malformations were probably not treatment related.

  10. Net energy and greenhouse gas emission evaluation of biodiesel derived from microalgae.

    Science.gov (United States)

    Batan, Liaw; Quinn, Jason; Willson, Bryan; Bradley, Thomas

    2010-10-15

    Biofuels derived from microalgae have the potential to replace petroleum fuel and first-generation biofuel, but the efficacy with which sustainability goals can be achieved is dependent on the lifecycle impacts of the microalgae-to-biofuel process. This study proposes a detailed, industrial-scale engineering model for the species Nannochloropsis using a photobioreactor architecture. This process level model is integrated with a lifecycle energy and greenhouse gas emission analysis compatible with the methods and boundaries of the Argonne National Laboratory GREET model, thereby ensuring comparability to preexisting fuel-cycle assessments. Results are used to evaluate the net energy ratio (NER) and net greenhouse gas emissions (GHGs) of microalgae biodiesel in comparison to petroleum diesel and soybean-based biodiesel with a boundary equivalent to "well-to-pump". The resulting NER of the microalgae biodiesel process is 0.93 MJ of energy consumed per MJ of energy produced. In terms of net GHGs, microalgae-based biofuels avoids 75 g of CO(2)-equivalent emissions per MJ of energy produced. The scalability of the consumables and products of the proposed microalgae-to-biofuels processes are assessed in the context of 150 billion liters (40 billion gallons) of annual production.

  11. Synthesis and antitubercular evaluation of imidazo[2,1-b][1,3,4]thiadiazole derivatives

    Directory of Open Access Journals (Sweden)

    Harun M. Patel

    2017-02-01

    Full Text Available In the present study, a series of imidazo[2,1-b][1,3,4]thiadiazole derivatives 5(a–j were synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral technique. The compounds were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain by using Alamar Blue susceptibility test as part of the TAACF TB screening program under direction of the US National Institutes of Health, the NIAID division. Among the tested compounds, 2-(1-methyl-1H-imidazol-2-yl-6-(4-nitrophenylimidazo[2,1-b][1,3,4]thiadiazole (5f has shown the highest (98% inhibitory activity with MIC of 3.14 μg/ml as compared to other tested compounds. Further, some potent compounds were also assessed for their cytotoxic activity against a mammalian Vero cell line using MTT assay. The results reveal that these compounds exhibit anti-tubercular activity at non-cytotoxic concentrations.

  12. Evaluation of Antibacterial Activity and Reactive Species Generation of N-Benzenesulfonyl Derivatives of Heterocycles.

    Science.gov (United States)

    Martínez, Sol Romina; Miana, Gisele Emilse; Albesa, Inés; Mazzieri, María Rosa; Becerra, María Cecilia

    2016-01-01

    Two N-benzenesulfonyl (BS) derivatives of 1,2,3,4-tetrahydroquinoline (THQ) were designed, prepared, and screened for antibacterial activity. This approach was based on combining the two privileged structures, BS and THQ, which are known to be active. The objective of this study was to evaluate the antibacterial activity of BS-THQ and its analogue 4-NH2BS-THQ, and to investigate the roles of reactive oxygen species and reactive nitrogen species in their lethality. Both showed bactericidal activity against Staphylococcus aureus ATCC 29213 and methicillin-resistant S. aureus (MRSA) ATCC 43300, with transmission electron microscopy revealing a disturbed membrane architecture. Furthermore, an increase of reactive oxygen species (ROS) in strains treated with BS-THQ with respect to the control was detected when fluorescent microscopy and spectrophotometric techniques were used. The analogue 4-NH2BS-THQ demonstrated a broader spectrum of activity than BS-THQ, with a minimum inhibitory concentration of 100 µg/mL against reference strains of S. aureus, Escherichia coli and Pseudomonas aeruginosa. The assayed compounds represent promising structures for the development of new synthetic classes of antimicrobials.

  13. The synthesis, structure and activity evaluation of pyrogallol and catechol derivatives as Helicobacter pylori urease inhibitors.

    Science.gov (United States)

    Xiao, Zhu-Ping; Ma, Tao-Wu; Fu, Wei-Chang; Peng, Xiao-Chun; Zhang, Ai-Hua; Zhu, Hai-Liang

    2010-11-01

    Some pyrogallol and catechol derivatives were synthesized, and their urease inhibitory activity was evaluated by using acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor, as positive control. The assay results indicate that many compounds have showed potential inhibitory activity against H. pylori urease. 4-(4-Hydroxyphenethyl)phen-1,2-diol (2a) was found to be the most potent urease inhibitor with IC(50)s of 1.5±0.2 μM for extracted fraction and 4.2±0.3 μM for intact cell, at least 10 times and 20 times lower than those of AHA (IC(50) of 17.2±0.9 μM, 100.6±13 μM), respectively. This finding indicate that 2a would be a potential urease inhibitor deserves further research. Molecular dockings of 2a into H. pylori urease active site were performed for understanding the good activity observed.

  14. COX inhibitors Indomethacin and Sulindac derivatives as antiproliferative agents: synthesis, biological evaluation, and mechanism investigation.

    Science.gov (United States)

    Chennamaneni, Snigdha; Zhong, Bo; Lama, Rati; Su, Bin

    2012-10-01

    Cyclooxygenase (COX) inhibitors Indomethacin and its structural analogs Sulindac exhibit cell growth inhibition and apoptosis inducing activities in various cancer cell lines via COX independent mechanisms. In this study, the molecular structures of Indomethacin and Sulindac were used as starting scaffolds to design novel analogs and their effects on the proliferation of human cancer cells were evaluated. Compared to Indomethacin and Sulindac inhibiting cancer cell proliferation with IC(50)s of more than 1 mM, the derivatives displayed significantly increased activities. Especially, one of the Indomethacin analogs inhibited the growth of a series of cancer cell lines with IC(50)s around 0.5 μM-3 μM. Mechanistic investigation revealed that the new analog was in fact a tubulin inhibitor, although the parental compound Indomethacin did not show any tubulin inhibitory activity. Tubulin polymerization assay indicated this compound inhibited tubulin assembly at high concentrations, but promoted this process at low concentrations which is a very unique mechanism. The binding mode of this compound in tubulin was predicted using the molecular docking simulation.

  15. Design, synthesis, structural elucidation, pharmacological evaluation of metal complexes with pyrazoline derivatives.

    Science.gov (United States)

    Muneera, M Sirajul; Joseph, J

    2016-10-01

    A bioactive pyrazoline derivatives have been synthesized by the base-catalyzed Claisen-Schmidt condensation of imidazole-2-carboxaldehyde with 1-acetyl-2-hydroxynaphthalene followed by cyclization with phenylhydrazine (L(1))/2,3-dimethylphenylhydrazine (L(2)) and 3-nitrophenylhydrazine (L(3)). The metal(II) complexes [Ni(II), Co(II), Cu(II) and Zn(II)] were formed by reacting the corresponding metal acetates with the ligands. All complexes were characterized by elemental analyses, electronic, IR, NMR, mass and ESR spectroscopic techniques. The synthesized metal complexes of pyrazoline compounds showed significant antibacterial activity against the organisms Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis and Salmonella typhii when compared with the standard antibiotic (Streptomycin). The ligands and their metal complexes were screened for antioxidant activity using DPPH radical scavenging and superoxide radical scavenging assay methods. All the complexes showed good free radical scavenging activity which is comparable to that of the standards. Among the metal complexes, the copper complex has showed higher activity. The results were indicated that 2-pyrazoline (structural core) and copper ion could be responsible for the potential candidate eliciting antioxidant activity. All compounds were evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis. The ligands and metal complexes were subjected to fluorescence properties and exhibited that the variable fluorescence emission behavior of complexes. It can be attributed to the combined effect of the substituents and naphthyl structural core present in the ligands.

  16. Histologic evaluation of effectiveness of Enamel Matrix Derivative in surgical defect of sheep tooth

    Directory of Open Access Journals (Sweden)

    Pak Nejad M.

    2001-09-01

    Full Text Available "nAbstract: The aim of the present study was the histological evaluation of Enamel Matrix Derivative (EMD effectiveness for regeneration of periodontal defects. EMD activates cementum synthesis, PDL and bone during the maturation stage of follicole. In this research, EMD was used in surgical defects of premolar teeth in four adult sheep. Muccoperiosteal flap was reflected in buccal site of teeth. The buccal bone plate was removed from mesial to distal in 4 mm depth. After eliminating the cementum by bur and its etching, EMD was applied on exposed dentine and flap was sutured. In opposite sites of those teeth (control sites the same process was performed without etching. After 100 days, sheep were sacrificed and histological study through light microscopic was performed on black sections of operation sites. The results showed that in test sites, regeneration of cementum and bone was 62/5% and 42/5-50% respectively. But in control sites regeneration of cementum and bone was 37.5% and 32/5-42/5% respectively. Also the migration of junctional epithelium in control sites was 8-10% more than test sites. The important point is that in test sites, cementum was completely attached to undermining dentine. But, in control sites, the gap between cementum and dentine was visible. As a result, this study suggests that EMD promotes periodontal regeneration, and EMD application is a successful achievement in regenerative periodontal therapy.

  17. Cytotoxic Evaluation of e-Liquid Aerosol using Different Lung-Derived Cell Models

    Directory of Open Access Journals (Sweden)

    Stefanie Scheffler

    2015-10-01

    Full Text Available The in vitro toxicological evaluation of e-liquid aerosol is an important aspect of consumer protection, but the cell model is of great significance. Due to its water solubility, e-liquid aerosol is deposited in the conducting zone of the respiratory tract. Therefore, primary normal human bronchial epithelial (NHBE cells are more suitable for e-liquid aerosol testing than the widely used alveolar cell line A549. Due to their prolonged lifespan, immortalized cell lines derived from primary NHBE cells, exhibiting a comparable in vitro differentiation, might be an alternative for acute toxicity testing. In our study, A549 cells freshly isolated NHBE cells and the immortalized cell line CL-1548 were exposed at the air-liquid interface to e-liquid aerosol and cigarette mainstream smoke in a CULTEX® RFS compact module. The cell viability was analyzed 24 h post-exposure. In comparison with primary NHBE cells, the CL-1548 cell line showed lower sensitivity to e-liquid aerosol but significantly higher sensitivity compared to A549 cells. Therefore, the immortalized cell line CL-1548 is recommended as a tool for the routine testing of e-liquid aerosol and is preferable to A549 cells.

  18. Synthesis and antiproliferative evaluation of novel 1,2,4-triazole derivatives incorporating benzisoselenazolone scaffold.

    Science.gov (United States)

    Li, Bao-Lin; Li, Bo; Zhang, Rui-Lian; Zhao, Ji-Jun; Wang, Xue-Feng; Liu, Yu-Ming; Shi, Yan-Ping; Liu, Jin-Biao; Chen, Bao-Quan

    2016-02-15

    A series of novel 1,2,4-triazole derivatives incorporating benzisoselenazolone scaffold were designed, synthesized and evaluated for their in vitro antiproliferative activities against human cancer cell lines SMMC-7721, Hela, A549, and normal cell lines L929 by CCK-8 assay. The preliminary bioassay results demonstrated that most of the tested compounds 3a-3n exhibited antiproliferation with different degrees, and some compounds showed better effects than positive controls ethaselen and 5-fluorouracil (5-FU) against various cancer cell lines. Among these compounds, compounds 3b and 3c displayed highly effective biological activities against SMMC-7721cells with IC50 values of 6.02 and 6.01 μM, respectively. Compound 3n showed significant antiproliferative activities against Hela cells with IC50 value of 3.94 μM. Compound 3n exhibited the best inhibitory effect against A549 cells with IC50 value 9.14 μM. Furthermore, most of the tested compounds showed weak cytotoxic effect against the normal cell lines L929. The pharmacological results suggest that the substituent groups are vital for improving the potency and selectivity of this class of compounds.

  19. Prospective evaluation of a Holter-ECG derived severity index for screening of sleep disordered breathing.

    Science.gov (United States)

    Maier, Christoph; Friedrich, Jörg; Katus, Hugo; Dickhaus, Hartmut

    To prospectively evaluate the applicability of a method to screen overnight Holter-ECGs for sleep disordered breathing (SDB) in an unselected clinical routine Holter sample. Holter-ECG recordings in 50 cardiologic inpatients were complemented with nocturnal respiratory polygraphy (PG). The respiratory event index (REI) and apnea/hypopnea index (AHI) from the PG served as a reference for an ECG-derived SDB severity estimate using a previously developed method. Agreement with the PG was investigated using Bland-Altman plots color-coded by ectopy level, and screening accuracy for REI≥15/h and AHI≥15/h was assessed. Prevalence for REI≥15/h was 52%, and 32% for AHI≥15/h. We observed better agreement of the ECG-based estimate with the REI compared to the AHI. Ectopy did not limit the detection of SDB. Binary screening for REI≥15/h provided excellent specificity of 0.96 with a sensitivity of 0.77. Ternary screening for AHI≥15/h yielded 16% borderline classifications and specificity/sensitivity of 0.96/0.86 for the remaining data. Screening of routine Holter-ECGs for sleep disordered breathing is reasonable and promises earlier identification of a significant part of patients at no additional cost. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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

    2015-01-01

    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. PMID:26300949

  1. Structure based design, synthesis and biological evaluation of amino phosphonate derivatives as human glucokinase activators.

    Science.gov (United States)

    Yellapu, Nanda Kumar; Kilaru, Ravendra Babu; Chamarthi, Nagaraju; Pvgk, Sarma; Matcha, Bhaskar

    2017-06-01

    Glucokinase (GK) is a potential therapeutic target of type 2 diabetes and GK activators (GKAs) represent a promising class of small organic molecules which enhance GK activity. Based on the configuration and conformation of the allosteric site of GK, we have designed a novel class of amino phosphonate derivatives in order to develop potent GKAs. The QSAR model developed using numerous descriptors revealed its potential with the best effective statistical values of RMSE=1.52 and r(2)=0.30. Moreover, application of this model on the present test set GKAs proved to be worthy to predict their activities as a better linear relationship was observed with RMSE=0.14 and r(2)=0.88. ADME studies and Lipinski filters encouraged them as safer therapeutics. The molecular dynamics and docking studies against the GK allosteric site revealed that all GKAs bind with best affinities and the complexes are strengthened by H-bonding, phosphonate salt bridges, hydrophobic and arene cat ionic interactions. Finally, in vitro evaluation with human liver GK revealed their potential to increase the GK activity by different folds. The results from QSAR, ADME, molecular docking and in vitro assays strongly suggested that the present molecules could be used as effective and safer therapeutics to control and manage type 2 diabetes. Copyright © 2017. Published by Elsevier Ltd.

  2. 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.

  3. Evaluation of a physically-based snow model with infrared and microwave satellite-derived estimates

    Science.gov (United States)

    Wang, L.

    2013-05-01

    Snow (with high albedo, as well as low roughness and thermal conductivity) has significant influence on the land-atmosphere interactions in the cold climate and regions of high elevation. The spatial and temporal variability of the snow distribution on a basin scale greatly determines the timing and magnitude of spring snowmelt runoff. For improved water resources management, a physically-based distributed snow model has been developed and applied to the upper Yellow River Basin to provide the outputs of snow variables as well as streamflows from 2001 to 2005. Remotely-sensed infrared information from MODIS satellites has been used to evaluate the model's outputs of spatially-distributed snow cover extent (SCE) and land surface temperature (LST); while the simulated snow depth (SD) and snow water equivalent (SWE) have been compared with the microwave information from SSM/I and AMSR-E satellites. In general, the simulated streamflows (including spring snowmelt) agree fairly well with the gauge-based observations; while the modeled snow variables show acceptable accuracies through comparing to various satellite-derived estimates from infrared or microwave information.;

  4. Design, synthesis, and biological evaluation of 4-phenylpyrrole derivatives as novel androgen receptor antagonists.

    Science.gov (United States)

    Yamamoto, Satoshi; Matsunaga, Nobuyuki; Hitaka, Takenori; Yamada, Masami; Hara, Takahito; Miyazaki, Junichi; Santou, Takashi; Kusaka, Masami; Yamaoka, Masuo; Kanzaki, Naoyuki; Furuya, Shuichi; Tasaka, Akihiro; Hamamura, Kazumasa; Ito, Mitsuhiro

    2012-01-01

    A series of 4-phenylpyrrole derivatives D were designed, synthesized, and evaluated for their potential as novel orally available androgen receptor antagonists therapeutically effective against castration-resistant prostate cancers. 4-Phenylpyrrole compound 1 exhibited androgen receptor (AR) antagonistic activity against T877A and W741C mutant-type ARs as well as wild-type AR. An arylmethyl group incorporated into compound 1 contributed to enhancement of antagonistic activity. Compound 4n, 1-{[6-chloro-5-(hydroxymethyl)pyridin-3-yl]methyl}-4-(4-cyanophenyl)-2,5-dimethyl-1H-pyrrole-3-carbonitrile exhibited inhibitory effects on tumor cell growth against the bicalutamide-resistant LNCaP-cxD2 cell line as well as the androgen receptor-dependent JDCaP cell line in a mouse xenograft model. These results demonstrate that this series of pyrrole compounds are novel androgen receptor antagonists with efficacy against prostate cancer cells, including castration-resistant prostate cancers such as bicalutamide-resistant prostate cancer.

  5. Synthesis and Biological Evaluation of New Ligustrazine Derivatives as Anti-Tumor Agents

    Directory of Open Access Journals (Sweden)

    Haimin Lei

    2012-04-01

    Full Text Available To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the “combination principle” in drug discovery. The ligustrazine derivatives’ anti-tumor activities were evaluated on the HCT-8, Bel-7402, BGC-823, A-549 and A2780 human cancer cell lines. In addition the angiogenesis activities were valued by the chick chorioallantoic membrane (CAM assay. 1,7-bis(4-(3,5,6-Trimethylpyrazin-2-yl-3-methoxyphenyl-1,6-heptadiene-3,5-dione (4 and 3 α,12 α-dihydroxy-5β-dholanic acid-3,5,6-trimethylpyrazin-2-methyl ester (5 not only displayed antiproliferative activities on these cancer cells, but also dramatically suppressed normal angiogenesis in CAM. The LD50 value of the compound 5 exceeded 3.0 g/kg by oral administration in mice.

  6. Synthesis and Evaluation of Ester Derivatives of 10-Hydroxycanthin-6-one as Potential Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Fei Zhao

    2016-03-01

    Full Text Available As part of our continuing research on canthin-6-one antimicrobial agents, a new series of ester derivatives of 10-hydroxycanthin-6-one were synthesized using a simple and effective synthetic route. The structure of each compound was characterized by NMR, ESI-MS, FT-IR, UV, and elemental analysis. The antimicrobial activity of these compounds against three phytopathogenic fungi (Alternaria solani, Fusarium graminearum, and Fusarium solani and four bacteria (Bacillus cereus, Bacillus subtilis, Ralstonia solanacearum, and Pseudomonas syringae were evaluated using the mycelium linear growth rate method and micro-broth dilution method, respectively. The structure-activity relationship is discussed. Of the tested compounds, 4 and 7s displayed significant antifungal activity against F. graminearum, with inhibition rates of 100% at a concentration of 50 μg/mL. Compounds 5, 7s, and 7t showed the best inhibitory activity against all the tested bacteria, with minimum inhibitory concentrations (MICs between 3.91 and 31.25 μg/mL. Thus, 7s emerged as a promising lead compound for the development of novel canthine-6-one antimicrobial agents.

  7. Synthesis and Evaluation of Ester Derivatives of 10-Hydroxycanthin-6-one as Potential Antimicrobial Agents.

    Science.gov (United States)

    Zhao, Fei; Dai, Jiang-Kun; Liu, Dan; Wang, Shi-Jun; Wang, Jun-Ru

    2016-03-21

    As part of our continuing research on canthin-6-one antimicrobial agents, a new series of ester derivatives of 10-hydroxycanthin-6-one were synthesized using a simple and effective synthetic route. The structure of each compound was characterized by NMR, ESI-MS, FT-IR, UV, and elemental analysis. The antimicrobial activity of these compounds against three phytopathogenic fungi (Alternaria solani, Fusarium graminearum, and Fusarium solani) and four bacteria (Bacillus cereus, Bacillus subtilis, Ralstonia solanacearum, and Pseudomonas syringae) were evaluated using the mycelium linear growth rate method and micro-broth dilution method, respectively. The structure-activity relationship is discussed. Of the tested compounds, 4 and 7s displayed significant antifungal activity against F. graminearum, with inhibition rates of 100% at a concentration of 50 μg/mL. Compounds 5, 7s, and 7t showed the best inhibitory activity against all the tested bacteria, with minimum inhibitory concentrations (MICs) between 3.91 and 31.25 μg/mL. Thus, 7s emerged as a promising lead compound for the development of novel canthine-6-one antimicrobial agents.

  8. Synthesis and Pharmacological Evaluation of Some New Pyrimidine Derivatives Containing 1,2,4-Triazole

    Directory of Open Access Journals (Sweden)

    Shantaram Gajanan Khanage

    2012-08-01

    Full Text Available Purpose: An efficient method has been described for synthesis of 6-(substituted aryl-4-(3,5-diphenyl-1H-1,2,4-triazol-1-yl-1, 6-dihydropyrimidine-2-thiol, as a beneficial antimicrobial, anticonvulsant and anticancer agents. Methods: The clalcones of title compounds were synthesized in three steps and subsequently these chalcones were further reacted with thiourea in the presence of KOH in ethanol, which led to the formation of dihydropyrimidine derivatives (4a-j. Compounds 4a-j were screened for their in vitro antimicrobial activity by agar well method and their anticonvulsant activity by the MES model. Anticancer activity of two newly synthesized heterocycles were evaluated at National Cancer Institute (NCI Maryland, USA against 60 cell lines of different human tumor at a single dose of 10-5M. Results: Compound 4b, 4c, 4d, 4i and 4j were exhibited significant antimicrobial potential against tested strains at 50μg/ml and 100μg/ml concentrations. Out of the ten compounds studied 4a, 4b, 4c, 4h and 4j showed comparable MES activity to Phenytoin and Carbamazepine after 0.5h. Tested compounds did not showed to be more potent than standard drugs after 4h. Compound 4a and 4d were found active on Non-Small Cell Lung Cancer (HOP-92. Conclusion: Ten noveldihydropyrimidine analogues has been synthesized, characterized and found to bepromising antibacterial, anticonvulsant and antitumor agents.

  9. 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

  10. Crystal structure of benzyl (E)-2-(3,4-di-meth-oxy-benzyl-idene)hydrazine-1-carbodi-thio-ate.

    Science.gov (United States)

    Tan, Yew-Fung; Break, Mohammed Khaled Bin; Tahir, M Ibrahim M; Khoo, Teng-Jin

    2015-02-01

    The title compound, C17H18N2O2S2, synthesized via a condensation reaction between S-benzyl di-thio-carbazate and 3,4-di-meth-oxy-benzaldehyde, crystallized with two independent mol-ecules (A and B) in the asymmetric unit. Both mol-ecules have an L-shape but differ in the orientation of the benzyl ring with respect to the 3,4-di-meth-oxy-benzyl-idine ring, this dihedral angle is 65.59 (8)° in mol-ecule A and 73.10 (8)° in mol-ecule B. In the crystal, the A and B mol-ecules are linked via pairs of N-H⋯S hydrogen bonds, forming dimers with an R 2 (2)(8) ring motif. The dimers are linked via pairs of C-H⋯O hydrogen bonds, giving inversion dimers of dimers. These units are linked by C-H⋯π inter-actions, forming ribbons propagating in the [100] direction.

  11. 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.

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

    Science.gov (United States)

    Zambrano, Francisco; Wardlow, Brian; Tadesse, Tsegaye

    2016-10-01

    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 (+30 years), 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 evaluate their applicability for agricultural drought evaluation 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-based precipitation estimates. 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-based estimates. Nine statistics were used to evaluate the performance of satellite products to estimate the amount and spatial distribution of historical rainfall across Chile. Hierarchical cluster analysis, k-means and singular value decomposition were used to

  13. Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives.

    Science.gov (United States)

    Jagu, Elodie; Djilali, Rachid; Pomel, Sébastien; Ramiandrasoa, Florence; Pethe, Stéphanie; Labruère, Raphaël; Loiseau, Philippe M; Blonski, Casimir

    2015-01-15

    A structure-activity relationship study on polyamine derivatives led to the synthesis and the determination of antikinetoplastid activity of 17 compounds. Among them, a spermidine derivative (compound 13) was specifically active in vitro against Leishmania donovani axenic amastigotes (IC50 at 5.4μM; Selectivity Index >18.5) and a spermine derivative (compound 28) specifically active against Trypanosoma brucei gambiense (IC50 at 1.9μM; Selectivity Index >52).

  14. Synthesis of Urea based Chalcone Derivatives and Evaluate its Biological Activity

    Directory of Open Access Journals (Sweden)

    Arpita Desai

    2016-05-01

    Full Text Available Chalcones have been the center of attraction for researchers from several decades due to nits innumerous therapeutic application, Efforts have been done in my research to synthesized chalcones and their derivatives that further reacts with various substituted aldehyde to give corresponding substituted chalcone derivatives. Now these derivatives on condensation with Guanidine nitrate gives the vast range of phenyl pyrimidine amine Derivatives. Structure elucidation of synthesized compound had been made on the basis of element analysis, 1H NMR Spectra studies. The microbial activity of the synthesized compounds has been studied against the species bacillus subtillis, staphylococcus aureus, Escherichia coli, and salmonella typhi.

  15. Vasodilation effect of 2-benzyl-5-hydroxy-6-methoxy-3, 4-dihydroisoquinolin-1-one.

    Science.gov (United States)

    Xu, Wei-Qi; Xiong, Zhi-Zheng; Chen, Ting-Ting; Gao, Xiao-Yan; Yu, Hang; Zhang, San-Qi; Cao, Yong-Xiao

    2012-08-01

    A 2-Benzyl-5-hydroxy-6-methoxy-3, 4-dihydroisoquinolin-1-one (ZC2) is a newly synthesized isoquinolinone compound. Its effect on vasodilation was evaluated in the present study. Isometric tension of rat artery rings was recorded by a sensitive myography system in vitro. The results showed that ZC2 relaxed rat mesenteric arteries pre-contracted by KCl, phenylephrine and 9, 11- dideoxy- 11α, 9α-epoxymethano-prostaglandin F2α (U46619), and abdominal aorta pre-contracted by KCl in a concentration-dependent manner. The ZC2-induced vasodilation was not affected by an endothelium denudation. ZC2 rightwards shifted the concentration-contraction curves, induced by KCl, phenylephrine, and 5-hydroxytryptamine (5-HT) in a non-parallel manner, which suggests that the vasodilation effects are most likely via voltage-dependent calcium channel (VDCC) and receptor-operated calcium channel (ROCC). Moreover, in Ca(2+)-free medium, ZC2 concentration-dependently depressed the vasoconstrictions induced by phenylephrine and CaCl(2), and decreased a contractile response induced by caffeine, which indicates a role of extracellular Ca(2+) influx inhibition through VDCC and ROCC, and intracellular Ca(2+) release from Ca(2+) store via the ryanodine receptors. Glibenclamide did not affect the vasodilation induced by ZC2, suggesting that ATP sensitive potassium channel is not involved in the vasodilation. The results indicate that ZC2 induces vasodilation by inhibiting the VDCC and ROCC, and receptormediated Ca(2+) influx and release. The inhibition of intracellular Ca(2+) release may be mediated via the ryanodine receptors.

  16. Effects of benzyl isothiocyanate on the reproduction of Meloidogyne incognita on Glycine max and Capsicum annuum

    Science.gov (United States)

    Reproduction of Meloidogyne incognita on Capsicum annuum or Glycine max was suppressed when infective juveniles (J2) were exposed to 0.03 millimolar benzyl isothiocyanate (BITC) for 2hr prior to inoculation of the host. Infectivity assessed by gall index was significantly reduced on both G. max (co...

  17. The Synthesis and Methanolysis of Benzyl Tosylates: An Advanced Organic Chemistry Laboratory Experiment.

    Science.gov (United States)

    Garst, Michael E.; Gribble, Gordon W.

    1984-01-01

    Describes a series of experiments (requiring six hours/week for six to eight weeks) involving the synthesis and methanolysis of substituted benzyl tosylates. The experiments provide students with experiences in kinetic data manipulation and an introduction and firm basis for structure-activity relationships and solvent effects in organic…

  18. Reductive coupling reaction of benzyl, allyl and alkyl halides in aqueous medium promoted by zinc

    Directory of Open Access Journals (Sweden)

    Sá Ana C. P. F. de

    2003-01-01

    Full Text Available Organic halides undergo reductive dimerization (Wurtz-type coupling promoted by zinc at room temperature in aqueous medium. The reaction yields are strongly enhanced by copper catalysis. This coupling procedure provides an efficient and simple method for the homocoupling of benzylic and allylic bromides and primary alkyl iodides.

  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. 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

    The Grignard addition reaction is known to be a reversible process with allylic reagents, but so far the reversibility has not been demonstrated with other alkylmagnesium halides. By using crossover experiments it has been established that the benzyl addition reaction is also a reversible transfo...

  1. "Decarbonization" of an imino N-heterocyclic carbene via triple benzyl migration from hafnium

    Science.gov (United States)

    An imino N-heterocyclic carbene underwent three sequential benzyl migrations upon reaction with tetrabenzylhafnium, resulting in complete removal of the carbene carbon from the ligand. The resulting eneamido-amidinato hafnium complex showed alkene polymerization activity comparable to that of a prec...

  2. Copper-catalyzed aerobic oxidative synthesis of aryl nitriles from benzylic alcohols and aqueous ammonia.

    Science.gov (United States)

    Tao, Chuanzhou; Liu, Feng; Zhu, Youmin; Liu, Weiwei; Cao, Zhiling

    2013-05-28

    Copper-catalyzed direct conversion of benzylic alcohols to aryl nitriles was realized using NH3(aq.) as the nitrogen source, O2 as the oxidant and TEMPO as the co-catalyst. Furthermore, copper-catalyzed one-pot synthesis of primary aryl amides from alcohols was also achieved.

  3. Temperature dependence of the lifetime of excited benzyl and other arymethyl radicals

    Energy Technology Data Exchange (ETDEWEB)

    Miesel, D.; Das, P.K.; Hug, G.L.; Bhattacharyya, K.; Fessenden, R.W.

    1986-08-06

    The temperature dependence of the fluorescence lifetime of benzyl, benzyl-d/sub 7/, ..cap alpha..-methylbenzyl, and triphenylmethyl radicals has been studied in 2-methyltetrahydroduran from 77 to 300 K. Temperature independent and unusual temperature dependent relaxation pathways are observed for the excited states of all four radicals. Activation energies for the temperature-dependent relaxation process are approx.1400 cm/sup -1/ for all these radicals, and frequency factors are in the range of (2-20) x 10/sup 11/ s/sup -1/. For Ph/sub 3/C radicals, the temperature-dependent process leads to observable photochemistry. However, no photochemistry is observed to result from the thermally activated relaxation of benzyl radicals. Possible pathways of these nonradiative decay processes are discussed and contrasted with the weak temperature dependence for the relaxation of diphenylmethyl radicals. It is proposed that the temperature-dependent route for the radiationless decay of benzyl radicals results from differential vibronic mixing of the two excited states, the 1/sup 2/A/sub 2/ and 2/sup 2/B/sub 2/ states. Most efficient in that mixing seems to be C-C stretching vibrational modes.

  4. Efficient synthesis of dibenzyl carbonates from benzyl halides and Cs2CO3

    Directory of Open Access Journals (Sweden)

    Yuxuan He

    2017-07-01

    Full Text Available A simple and efficient protocol for the synthesis of dibenzyl carbonates has been developed. The reaction was accomplished using benzyl halides and Cs2CO3 as the starting materials in the presence of atmospheric pressure of CO2, affording a variety of the dibenzyl carbonates in good to excellent yields under rather mild conditions.

  5. Pharmacokinetics in Elderly Women of Benzyl Alcohol From an Oil Depot

    NARCIS (Netherlands)

    Kalicharan, Raween; El Amrani, Mohsin; Schot, Peter; Vromans, Herman|info:eu-repo/dai/nl/073088803

    2016-01-01

    Pharmaceutical oil depots are meant to release active substances at a sustained rate. Most of these depots contain benzyl alcohol (BOH) to facilitate the production and administration. Because BOH changes the solubility of components in both the body fluid and the oil formulation, it is relevant to

  6. Support influences in the Pd-catalyzed racemization and dynamic kinetic resolution of chiral benzylic amines

    NARCIS (Netherlands)

    Parvulescu, A.N.; Jacobs, P.A.; De Vos, D.E.

    2009-01-01

    The acid–base properties of the supports for Pd catalysts strongly affect their performance in racemization and dynamic kinetic resolution (DKR) of chiral benzylic amines. The need for a basic support was proven by comparing the racemization results obtained for Pd on silica, on LDH (layered double

  7. Effect of cotton pectin content and bioscouring on alkyl-dimethyl-benzyl-ammonium chloride adsorption

    Science.gov (United States)

    Our previous research has shown both the rate and the total amount of alkyl-dimethyl-benzyl-ammonium chloride (ADBAC) exhausted from a bulk solution of ADBAC are significantly greater for greige cotton nonwovens than cotton nonwovens that have been both scoured and bleached. The presence of pectin ...

  8. Growing up Radical: Investigation of Benzyl-Like Radicals with Increasing Chain Lengths

    Science.gov (United States)

    Korn, Joseph A.; Jawad, Khadija M.; Hewett, Daniel M.; Zwier, Timothy S.

    2015-06-01

    Combustion processes involve complex chemistry including pathways leading to polyaromatic hydrocarbons (PAHs) from small molecule precursors. Resonance stabilized radicals (RSRs) likely play an important role in the pathways to PAHs due to their unusual stability. Benzyl radical is a prototypical RSR that is stabilized by conjugation with the phenyl ring. Earlier work on α-methyl benzyl radical showed perturbations to the spectroscopy due to a hindered methyl rotor. If the alkyl chain is lengthened then multiple conformations become possible. This talk will discuss the jet-cooled spectroscopy of α-ethyl benzyl radical and α-propyl benzyl radical produced from the discharge of 1-phenyl propanol and 1-phenyl butanol respectively. Electronic spectra were obtained via resonant two-photon ionization, and IR spectra were obtained by resonant ion-dip infrared spectroscopy. Kidwell, N. M.; Reilly, N. J.; Nebgen, B.; Mehta-Hurt, D. N.; Hoehn, R. D.; Kokkin, D. L.; McCarthy, M. C.; Slipchenko, L. V.; Zwier, T. S. The Journal of Physical Chemistry A 2013, 117, 13465.

  9. Adsorption of alkyl-dimethyl-benzyl-ammonium chloride on differently pretreated nonwoven cotton substrate

    Science.gov (United States)

    The adsorption of alkyl-dimethyl-benzyl-ammonium chloride (ADBAC), a cationic surfactant commonly employed as an antimicrobial agent, on greige, alkaline scoured, and bleached nonwoven cotton fabrics was investigated at varying surfactant concentrations and liquor ratios using UV-vis absorption spec...

  10. 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.

  11. Inhibition of a Gold-Based Catalyst in Benzyl Alcohol Oxidation: Understanding and Remediation

    NARCIS (Netherlands)

    Skupien, E.; Berger, R.J.; Santos, V.P.; Gascon, J.; Makkee, M.; Kreutzer, M.T.; Kooyman, P.J.; Moulijn, J.A.; Kapteijn, F.

    2014-01-01

    Benzyl alcohol oxidation was carried out in toluene as solvent, in the presence of the potentially inhibiting oxidation products benzaldehyde and benzoic acid. Benzoic acid, or a product of benzoic acid, is identified to be the inhibiting species. The presence of a basic potassium salt (K2CO3 or KF)

  12. Development, optimization and biological evaluation of chitosan scaffold formulations of new xanthine derivatives for treatment of type-2 diabetes mellitus.

    Science.gov (United States)

    Lupascu, Florentina Geanina; Dash, Mamoni; Samal, Sangram Keshari; Dubruel, Peter; Lupusoru, Catalina Elena; Lupusoru, Raoul-Vasile; Dragostin, Oana; Profire, Lenuta

    2015-09-18

    New xanthine derivatives as antidiabetic agents were synthesized and new chitosan formulations have been developed in order to improve their biological and pharmacokinetic profile. Their physicochemical properties in terms of particle size, morphology, swelling degree, crystalline state, the loading efficiency as well as in vitro release and biodegradation rate were evaluated. According to the results the optimized formulations have a high drug loading efficiency (more than 70%), small particle size, a good release profile in the simulated biological fluids (the percentage of cumulative release being more than 55%) and improved biodegradation rate in reference with chitosan microparticles. The presence of xanthine derivatives (6, 7) in chitosan microparticles was demonstrated by means of FTIR analysis. The X-ray diffraction (XRD) proved that xanthine derivatives present a crystalline state. The biological evaluation assays confirmed the antioxidant and antidiabetic effects of the xanthine derivatives (6, 7) and their chitosan formulations (CS-6, CS-7). Xanthine derivative 6 showed a high antiradical scavenging effect (DPPH remaining=41.78%). It also reduced the glucose blood level with 59.30% and recorded level of glycosylated hemoglobin was 4.53%. The effect of its chitosan formulation (CS-6) on the level of blood glucose (114.5mg/dl) was even more intense than the one recorded by pioglitazone (148.5mg/dl) when used as standard antidiabetic drug. These results demonstrated the potential application of xanthine derivative 6 and its chitosan formulation (CS-6) in the treatment of the diabetes mellitus syndrome.

  13. Evaluation of 2 celecoxib derivatives: analgesic effect and selectivity to cyclooxygenase-2/1

    Institute of Scientific and Technical Information of China (English)

    Zhi-hong LU; Xiao-yun XIONG; Bang-le ZHANG; Guo-cheng LIN; Yu-xiang SHI; Zhen-guo LIU; Jing-ru MENG; Yu-mei ZHOU; Qi-bing MEI

    2005-01-01

    Aim: To evaluate the analgesic effects of 2 celecoxib derivatives and their inhibitory effects on cyclooxygenase (COX). Methods: Four antinociceptive assays were used: the acetic acid-induced writhing test, hot plate test, hot tail-flick test and formalin test. Three doses were used in the analgesic assays and ED50 values were calculated. For the selectivity assay, macrophages were incubated with test compounds at various concentrations and then stimulated with calcimycin or lipopolysaccharide (LPS). The amounts of 6-keto-prostaglandin F1α (6-keto-PGF1α)and prostaglandin E2 (PGE2) in the supernatant were examined by radioimmunoassay (RIA). The selectivity of the test compounds was expressed as the IC50,COX-1/IC50,COX-2 value. Results: Celecoxib and its 2 derivatives had a significant analgesic effect. The ED50 values of celecoxib, PC-406 and PC-407 were 94.2, 67.9, and 63.3mg/kg, respectively, for the acetic acid-induced writhing test; 104.7, 89.1, and 30.0mg/kg, respectively, for the hot tail-flick response test; 60.7, 56.7, and 86.2 mg/kg,respectively, for the hot plate response test; 67.1,55.8, and 68.8 mg/kg, respectively,for the formalin-induced response. That is, the ED50 of PC-406 was the lowest for the formalin and hot plate tests, which focus on changes above the spinal cord level; however, the ED50 of PC-407 was lowest for the tail-flick and writhing tests,which focus on changes at the spinal cord level. Celecoxib and PC-407 inhibited COX-1 with IC50 values of 39.8 and 27.5 nmol/L, respectively. PC-406 inhibited COX-1 with an IC50 value of more than 1000 nmol/L. The IC50 values for the effect of celecoxib, PC-406 and PC-407 on COX-2 were 4.8, 8.9, and 1.9 nmol/L respectively.The IC50,COX-1/IC50,COX-2 ratios for celecoxib and PC-407 were 8.3 and 14.4, respectively. For PC-406, the ratio was greater than 112.2. Conclusion: Derivatives of celecoxib via substitution with an isopropyl or naphthyl group at the 5 position in the pyrazole ring still have

  14. 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

  15. Evaluation of bovine-derived lacteal complex supplementation on gene expression in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Clerici M

    2011-09-01

    Full Text Available Mario Clerici1,2, Emmanuel Pauze3, Arienne de Jong3, Mara Biasin1, Larry E Miller41Department of Biomedical Sciences and Technology, University of Milan, Milan, Italy; 2Don C Gnocchi Foundation, IRCCS, Milan, Italy; 3Sprim Advanced Life Sciences, Milan, Italy; 4Sprim USA, San Francisco, CA, USAAbstract: We conducted an evaluation of gene expression associated with innate and adaptive immunity in a double-blind ex vivo mouse study using a bovine-derived dietary ingredient (Ai/E10®, Health Technology Resources, Inc., Scottsdale, AZ, USA. BALB/c female mice (5–6 weeks of age were fed chewy granola bars supplemented with (Test or without (Control Ai/E10 for 10 days. After the feeding period, the animals were sacrificed and spleen cells were isolated and incubated with lipopolysaccharide and phorbol myristate acetate-ionomycin. RNA was extracted and mRNA expression of 84 genes involved in innate and acquired immunity was determined with real-time PCR arrays. Numerous genes associated with innate and adaptive immunity were upregulated in the Test group when stimulated with mitogens. Significant upregulation was observed in 30% (25 of 84 of genes upon lipopolysaccharide stimulation and in 14% (12 of 84 of genes upon phorbol myristate acetate + ionomycin stimulation in the Test group relative to Controls. This study illustrates that Ai/E10 supplementation results in significant and specific upregulation of genes associated with innate and adaptive immunity in mice. Notably, this effect was observed only in stimulated cultures.Keywords: dietary supplementation, immunomodulation, mice

  16. 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.

  17. Evaluation of IASI derived dust aerosols characteristics over the tropical belt

    Science.gov (United States)

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

    2013-11-01

    IASI-derived monthly mean infrared (10 μm) dust aerosol optical depth (AOD) and altitude are evaluated against ground based AERONET measurements of the 500 nm coarse mode AOD and CALIOP measurements of the altitude at 38 AERONET sites within the tropical belt (30° N-30° S). The period covered extends from July 2007 to December 2012. The evaluation goes through the analysis of Taylor diagrams and box and whiskers plots, separating situations over sea and over land. Concerning AOD, the overall correlation for the sites over sea comes to 0.88 for 713 items (IASI and AERONET monthly mean bins). The overall normalized standard deviation is of 0.96. Over land, essentially desert, correlation is of 0.74 for 582 items and the normalized standard deviation is of 0.87. 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 within the boundary layer (particularly for sites close to active sources) to which IASI, as any thermal infrared sounder, is poorly sensitive contrary to AERONET. Concerning altitude over sea, correlation is of 0.78 for 925 items and the normalized standard deviation is of 1.03. Results over land, essentially over deserts, are not satisfactory for a majority of sites. To the reasons listed above for the AOD must be added the smaller IASI signal induced by the altitude compared to the signal induced by the AOD. Site by site, disparities appear that we estimate being principally due to either the insufficient number of AERONET observations throughout the period considered, to the complexity of the situation mixing several aerosol types (case of the Persian Gulf, for example), to surface heterogeneities (elevation, emissivity, etc.), or to the use of a single aerosol model ("MITR"). Results using another aerosol model with different refractive indices are presented and discussed. We conclude that the present

  18. The novel primaquine derivatives of N-alkyl, cycloalkyl or aryl urea: synthesis, cytostatic and antiviral activity evaluations.

    Science.gov (United States)

    Dzimbeg, G; Zorc, B; Kralj, M; Ester, K; Pavelić, K; Andrei, G; Snoeck, R; Balzarini, J; De Clercq, E; Mintas, M

    2008-06-01

    The novel urea primaquine derivatives 3a-i were prepared by aminolysis of benzotriazolide 2 with the corresponding amine in the presence or absence of triethylamine. Compound 2 was prepared by acylation of primaquine with 1-benzotriazole carboxylic acid chloride. Among all compounds evaluated, the pyridine derivative 3h exhibited the best cytostatic activities against colon carcinoma, human T-lymphocyte and murine leukemia. However, this compound showed also rather marked cytotoxicity towards human normal fibroblasts. The highest selectivity in the inhibitory effects on human malignant tumor cell lines vs. normal fibroblasts was found for ureas 3c, 3d and 3g. Results of broad antiviral evaluation showed that pyridine and phenethyl derivatives of urea 3h and 3g exhibited some selective inhibition against cytomegalovirus.

  19. Bis-(1-2-benzopyran-1-one) derivatives: Synthesis and antimicrobial evaluation

    Indian Academy of Sciences (India)

    Poonam Kumar Koppula; Nalini Purohit

    2013-11-01

    The aim of the present study was to synthesize isocoumarin heterocycles and to elucidate the potential role of these compounds as biological active agents. A new series of isocoumarin derivatives containing two six-membered lactone rings is reported. 3-Aroyl-substituted isocoumarins (3) obtained by condensing 2-carboxy benzaldehyde (1) with bromoacetophenone derivatives (2) was further reacted with different aromatic aldehydes (4) affording bis-(1-2-benzopyran-1-one) derivatives (5). This short review compiles examples of most promising antibacterial, antifungal and analgesic bis-(1H-2-benzopyran-1-one) derivatives. The products were characterized on the basis of analytical and spectral (IR, 1HNMR, C13NMR, Mass) data. The biological activity study revealed that all compounds showed promising activities and bis-(1-2-benzopyran-1-one) derivatives (5) were found to be more active than 3-aroyl-substituted isocoumarins (3).

  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. Synthetic scope, computational chemistry and mechanism of a base induced 5-endo cyclization of benzyl alkynyl sulfides

    Science.gov (United States)

    Motto, John M.; Castillo, Álvaro; Montemayer, Laura K.; Sheepwash, Erin E.

    2011-01-01

    We present an experimental and computational study of the reaction of aryl substituted benzyl 1-alkynyl sulfides with potassium alkoxide in acetonitrile, which produces 2-aryl 2,3-dihydrothiophenes in poor to good yields. The cyclization is most efficient with electron withdrawing groups on the aromatic ring. Evidence indicates there is rapid exchange of protons and tautomerism of the alkynyl unit prior to cyclization. Theoretical calculations were also conducted to help rationalize the base induced 5-endo cyclization of benzyl 1-propynyl sulfide (1a). The potential energy surface was calculated for the formation of 2,3-dihydrothiophene in a reaction of benzyl 1-propynyl sulfide (1a) with potassium methoxide. Geometries were optimized with CAM-B3LYP/6-311+G(d,p) in acetonitrile with the CPCM solvent model. It is significant that the benzyl propa-1,2-dien-1-yl sulfane (6) possessed a lower benzylic proton affinity than the benzyl prop-2-yn-1-yl sulfane (8) thus favoring the base induced reaction of the former. From benzyl(propa-1,2-dien-1-yl sulfane (6), 2,3-dihydrothiophene can be formed via a conjugate base that undergoes 5-endo-trig cyclization followed by a protonation step. PMID:21442022

  2. 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 aberrati

  3. Investigation of comparative efficacy of eugenol and benzyl benzoate in therapy of sheep mange

    Directory of Open Access Journals (Sweden)

    Jezdimirović Milanka

    2010-01-01

    Full Text Available The acaricide efficacy, tolerance and safety of eugenol (10 and 20 % in the treatment of sarcoptic mange in sheep have been investigated. The results were compared with those corresponding for benzyl benzoate (25 %, which was applied to sheep in the same way. The treatment was applied on sheep three times in one-week intervals. Skin scrapings were sampled seven days after each treatment, as well as twenty-eight days following the third one. The changes on the skin were quantified and the mean recovery response (MRR was calculated. The clinical efficacy was assessed according to the MRR and the number of mites in the samples. Following the first treatment 10%eugenol was not significantly less efficacious in comparison with the higher concentration. Having been applied twice 20% eugenol was significantly more efficacious when compared to the lower concentration, which remained the same seven and twenty-eight days after the third application. The efficacy of 10% eugenol in the therapy of mange was significantly higher in comparison with benzyl benzoate following one, two or three administrations. The efficacy of benzyl benzoate four weeks after the third treatment was still significantly lower in comparison with 10% eugenol. The efficacy of 20% eugenol was significantly higher in comparison with its lower concentration as well as that of benzyl benzoate, following the second, and seven and twenty-eight days after the third one. No signs of local or systemic intolerance were observed in sheep treated with either 10 or 20% eugenol, or 25 % benzyl benzoate. .

  4. Antimicrobial activity of cobalst(II complexes with 2-aminobenzimidazole derivatives

    Directory of Open Access Journals (Sweden)

    Podunavac-Kuzmanović Sanja O.

    2004-01-01

    Full Text Available Cobalt(II chloride reacts with 2-aminobenzimidazole derivatives to give complexes of the formula [CoL2Cl2], where L=2-aminobenzimidazole 1-benzyl-2-aminobenzimidazole and 1-(4-methylbenzyl-2-aminobenzimidazole. All the ligands and their cobalt(II complexes were evaluated for their in vitro antimicrobial activity against Pseudomonas aeruginosa, Bacillus sp. Staphylococcus aureus, Sarcina lutea and Saccharomyces cerevisiae. The minimum inhibitory concentration (MIC was determined for all ligands and their complexes. It was found that tested compounds were more active against gram-positive than gram-negative bacteria. None of the compounds were significantly effective against yeast Saccharomyces cerevisiae, except 2-aminobenzimidazole complex, which moderately inhibited the growth of yeast. 1-(4-methylbenzil-2-aminobenzimidazole was found to be slightly active against Saccharomyces cerevisiae. The same ligand showed the lowest MIC value of 60 (g/ml against Pseudomonas aeruginosa, as well as 125 (g/ml, against Bacillus sp. and Sarcina lutea. The MIC value of its cobalt(II complex was 60 (g/ml against Pseudomonas aeruginosa. Cobalt(II complex with 1-benzyl-2-aminobenzimidazole showed the lowest MIC value of 60 (g/ml against Staphylococcus aureus. The effect of ligand and complex structure on the antimicrobial activity was discussed.

  5. Evaluation of Factors Affecting Cesium Extraction Performance by Calix[4]Arene Derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Rumppe, J.L.; Delmau, L.

    2004-01-01

    Novel aza-crown derivatives of dioctyloxy-calix[4]arene crown-6 were examined for their cesium extraction performance at different pH levels. These studies are of interest in addressing high-level waste tank remediation and the removal of 137Cs, a major contributor to heat and radiation generation. Preliminary studies were done to assess the performance of these calixarene compounds under varying conditions. Results showed an increase of cesium extraction with pH as well as expected trends in diluent effects and anion selectivity. Poor extraction performance of some aza-crown derivatives raised questions regarding the possibility of intramolecular hydrogen-bonding. A novel methylated derivative was used to address these questions. Additional experiments were conducted to determine the extraction effect on pH. Results indicate an increase in cesium extraction with pH, as shown in preliminary studies. Mono-aza derivatives were shown to exhibit better cesium extraction performance than their di-aza counterparts. The methylated derivative showed poorer extraction performance than the non-methylated derivative, indicating that completely removing the possibility of intramolecular hydrogen-bonding has negative effects on extraction performance. This suggests that the hydrogen-bonding facilitates anion co-extraction, which would lead to better overall extraction. Mono-aza derivatives were shown to cause unexpected changes in pH. This could possibly be attributed to protonation of the calix crown.

  6. 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

  7. 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.

  8. Benzothiazole incorporated thiazolidin-4-ones and azetidin-2-ones derivatives: Synthesis and in vitro antimicrobial evaluation

    Directory of Open Access Journals (Sweden)

    Sadaf J. Gilani

    2016-11-01

    Full Text Available In this study, a series of novel thiazolidin-4-ones (5a–g and azetidin-2-ones (6a–g were synthesized from N-(6-chlorobenzo[d]thiazol-2-ylhydrazine carboxamide derivatives of the benzothiazole class. Antimicrobial properties of the title compound derivatives were investigated against one Gram (+ bacteria (Staphylococcus aureus, three Gram (− bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and five fungi (Candida albicans, Aspergillus niger, Aspergillus flavus, Monascus purpureus and Penicillium citrinum using serial plate dilution method. The investigation of antibacterial and antifungal screening data revealed that all the tested compounds showed moderate to good inhibition at 12.5–200 μg/mL in DMSO. It has been observed that azetidin-2-ones derivatives are found to be more active than thiazolidin-4-ones derivatives against all pathogenic bacterial and fungal strains.

  9. Synthesis and evaluation of phenylalanine-derived trifluoromethyl ketones for peptide-based oxidation catalysis.

    Science.gov (United States)

    Featherston, Aaron L; Miller, Scott J

    2016-10-15

    We report the synthesis of phenylalanine-derived trifluoromethyl ketones for the in situ generation of dioxiranes for the purpose of oxidation catalysis. The key features of this synthesis include the use of a masked ketone strategy and a Negishi cross-coupling to access the parent amino acid. The derivatives can be readily incorporated into a peptide for use in oxidation chemistry and exhibit good stability and reactivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Synthesis and biological evaluation of quinoxaline di-N-oxide derivatives with in vitro trypanocidal activity.

    Science.gov (United States)

    Pérez-Silanes, Silvia; Torres, Enrique; Arbillaga, Leire; Varela, Javier; Cerecetto, Hugo; González, Mercedes; Azqueta, Amaya; Moreno-Viguri, Elsa

    2016-02-01

    We report the synthesis and in vitro activity against Trypanosoma cruzi epimastigotes of 15 novel quinoxaline derivatives. Ten of the derivatives presented IC50 values lower than the reference drugs Nfx and Bzn; four of them standed out with IC50 values lower than 1.5 μM. Moreover, unspecific cytotoxicity and genotoxicity studies are also reported. Compound 14 showed a SI higher than 24, whereas compound 10 was the only one that was negative in the genotoxicity screening.

  12. Synthesis and Evaluation of 2,4-Disubstituted Quinazoline Derivatives with Potent Anti-Angiogenesis Activities

    Directory of Open Access Journals (Sweden)

    Guangjin Yu

    2014-06-01

    Full Text Available A series of 2,4-disubstituted quinazoline derivatives were designed and synthesized. The biological results showed that most of quinazoline derivatives exhibited potent antiproliferative activities against a panel of three tumor cell lines and a good inhibitory effect against the adhesion and migration of human umbilical vein endothelial cells (HUVECs. Among these compounds, 11d was the most potent agent, that also exhibited the highest anti-angiogenesis activities in the chick embryo chorioallantoic membrane (CAM assay.

  13. Synthesis and biological evaluation of quinoxaline di-N-oxide derivatives with in vitro trypanocidal activity

    OpenAIRE

    Perez-Silanes, S. (Silvia); Torres, E; L. Arbillaga; Varela, J; H. Cerecetto; Gonzalez, M.; Azqueta, A.; Moreno-Viguri, E. (Elsa)

    2016-01-01

    Abstract: We report the synthesis and in vitro activity against T. cruzi epimastigotes of 15 novel quinoxaline derivatives. Ten of the derivatives presented IC50 values lower than the reference drugs Nfx and Bzn; four of them standed out with IC50 values lower than 1.5 M. Moreover, unspecific cytotoxicity and genotoxicity studies are also reported. Compound 14 showed a SI higher than 24, whereas compound 10 was the only one that was negative in the genotoxicity screening.

  14. 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

  15. 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; Fattah, Azza M Abdel; Attaby, Fawzy A; Al-Shayea, Oqba N

    2014-01-17

    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.

  16. 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.

  17. Synthesis and evaluation of structurally constrained quinazolinone derivatives as potent and selective histamine H3 receptor inverse agonists.

    Science.gov (United States)

    Nagase, Tsuyoshi; Mizutani, Takashi; Sekino, Etsuko; Ishikawa, Shiho; Ito, Sayaka; Mitobe, Yuko; Miyamoto, Yasuhisa; Yoshimoto, Ryo; Tanaka, Takeshi; Ishihara, Akane; Takenaga, Norihiro; Tokita, Shigeru; Sato, Nagaaki

    2008-11-13

    A series of structurally constrained derivatives of the potent H 3 inverse agonist 1 was designed, synthesized, and evaluated as histamine H 3 receptor inverse agonists. As a result, the N-cyclobutylpiperidin-4-yloxy group as in 2f was identified as an optimal surrogate structure for the flexible 1-pyrrolidinopropoxy group of 1. Subsequent optimization of the quinazolinone core of 2f revealed that substitution at the 5-position of the quinazolinone ring influences potency. Representative derivatives 5a and 5s showed improved potency in a histamine release assay in rats and a receptor occupancy assay in mice.

  18. Synthesis and Biological Evaluation of Novel Aryl-2H-pyrazole Derivatives as Potent Non-purine Xanthine Oxidase Inhibitors.

    Science.gov (United States)

    Sun, Zhi-Gang; Zhou, Xiao-Jing; Zhu, Ming-Li; Ding, Wen-Ze; Li, Zhen; Zhu, Hai-Liang

    2015-01-01

    A series of aryl-2H-pyrazole derivatives were synthesized and evaluated for inhibitory activity against xanthine oxidase in vitro as potent xanthine oxidase inhibitors. Among them, 2 aryl-2H-pyrazole derivatives showed significant inhibitory activities against xanthine oxidase. Compound 19 emerged as the most potent xanthine oxidase inhibitor (IC50=9.8 µM) in comparison with allopurinol (IC50=9.5 µM). The docking study revealed that compound 19 might have strong interactions with the active site of xanthine oxidase. This compound is thus a new candidate for further development for the treatment of gout.

  19. Synthesis and biological evaluation of a new series of 2-amino-3-aroyl thiophene derivatives as agonist allosteric modulators of the A1 adenosine receptor. A position-dependent effect study.

    Science.gov (United States)

    Romagnoli, Romeo; Baraldi, Pier Giovanni; Lopez-Cara, Carlota; Cruz-Lopez, Olga; Moorman, Allan R; Massink, Arnault; IJzerman, Adriaan P; Vincenzi, Fabrizio; Borea, Pier Andrea; Varani, Katia

    2015-08-28

    The 2-amino-3-(p-chlorobenzoyl)thiophene scaffold has been widely employed as a pharmacophore for the identification of small molecules acting as allosteric modulators at the adenosine A1 receptor. A new series of 2-amino-3-(p-chlorobenzoyl)-4-benzyl-5-arylthiophene derivatives, characterized by the absence as well as the presence of electron-releasing or electron-withdrawing groups on the phenyl ring at the 4- and 5-positions of the thiophene ring, were identified as positive allosteric enhancers at the adenosine A1 receptor in binding (saturation, competition and dissociation kinetics) and functional assays. To better understand the positional requirements of substituents on the 2-amino-3-(p-chlorobenzoyl)thiophene core, the corresponding regioisomeric 4-aryl-5-benzylthiophene analogues were synthesized and found to possess reduced allosteric enhancer activity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  20. 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

  1. 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

  2. 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.

  3. Evaluation of antimicrobial activity of extracts of Tibouchina candolleana (melastomataceae, isolated compounds and semi-synthetic derivatives against endodontic bacteria

    Directory of Open Access Journals (Sweden)

    Fernanda M. dos Santos

    2012-06-01

    Full Text Available This work describes the phytochemical study of the extracts from aerial parts of Tibouchina candolleana as well as the evaluation of the antimicrobial activity of extracts, isolated compounds, and semi-synthetic derivatives of ursolic acid against endodontic bacteria. HRGC analysis of the n-hexane extract of T. candolleana allowed identification of b-amyrin, a-amyrin, and b-sitosterol as major constituents. The triterpenes ursolic acid and oleanolic acid were isolated from the methylene chloride extract and identified. In addition, the flavonoids luteolin and genistein were isolated from the ethanol extract and identified. The antimicrobial activity was investigated via determination of the minimum inhibitory concentration (MIC using the broth microdilution method. Amongst the isolated compounds, ursolic acid was the most effective against the selected endodontic bacteria. As for the semi-synthetic ursolic acid derivatives, only the methyl ester derivative potentiated the activity against Bacteroides fragilis.

  4. A domino Knoevenagel hetero-Diels-Alder reaction for the synthesis of polycyclic chromene derivatives and evaluation of their cytotoxicity.

    Science.gov (United States)

    Reddy, B V Subba; Divya, Baddula; Swain, Manisha; Rao, T Prabhakar; Yadav, J S; Vishnu Vardhan, M V P S

    2012-03-01

    A novel octahydrochromeno[4,3-a]xanthen-1(2H)-one derivatives has been prepared using 10mol% dl-proline in ethanol via a domino Knoevenagel hetero-Diels-Alder reaction of alkene-tethered chromene-3-carboxaldehyde with cyclic 1,3-diketones. This is not only the first example on the preparation of highly diastereoselective pentacyclic chromene derivatives from alkene appended chromene-3-carboxaldehyde in one-pot process at ambient temperature but also preliminary evaluation of the cytotoxic activity of these chromene derivatives. Some of these compounds are found to exhibit potent cytotoxicity against two carcinoma cell lines A549 and B-16. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. 1,2,4-Triazolo[1,5-a]quinoxaline derivatives: synthesis and biological evaluation as adenosine receptor antagonists.

    Science.gov (United States)

    Catarzi, Daniela; Colotta, Vittoria; Varano, Flavia; Filacchioni, Guido; Martini, Claudia; Trincavelli, Letizia; Lucacchini, Antonio

    2004-02-01

    Since most of the reported adenosine receptor antagonists are 2-(hetero)aryl-substituted tricyclic heteroaromatic derivatives, in the present study we report the synthesis and the biological evaluation of a new set of 4-amino-1,2,4-triazolo[1,5-a]quinoxalines containing at position-2 an ethyl carboxylate group or a hydrogen atom. The structure-activity relationships on these compounds were in accordance with those of a previously reported series of analogous size and shape, thus suggesting a similar A(1)-binding mode. In particular, the binding data indicate that alkylation of the 4-amino group of these derivatives lead to potent A(1)-receptor antagonists. Moreover, as new results, this study has pointed out that the ethyl 2-carboxylate group can advantageously replace the 2-(hetero)aryl ring of previously reported triazoloquinoxaline derivatives, affording an ameliorated interaction with the A(1)-receptor subtype.

  6. Synthesis and evaluation of chalcone derivatives as inhibitors of neutrophils' chemotaxis, phagocytosis and production of reactive oxygen species.

    Science.gov (United States)

    Bukhari, Syed N A; Tajuddin, Yasmin; Benedict, Vannessa J; Lam, Kok W; Jantan, Ibrahim; Jalil, Juriyati; Jasamai, Malina

    2014-02-01

    Inhibitory effects on neutrophils' chemotaxis, phagocytosis and production of reactive oxygen species (ROS) are among the important targets in developing anti-inflammatory agents and immunosuppressants. Eight series of chalcone derivatives including five newly synthesized series were assessed for their inhibitory effects on chemotaxis, phagocytosis and ROS production in human polymorphonuclear neutrophils (PMNs). Inhibition of PMNs' chemotaxis and phagocytosis abilities were investigated using the Boyden chamber technique and the Phagotest kit, respectively, while ROS production was evaluated using luminol- and lucigenin-based chemiluminescence assay. The new derivatives (4d and 8d), which contain 4-methylaminoethanol functional group were active in all the assays performed. It was also observed that some of the compounds were active in inhibiting chemotaxis while others suppressed phagocytosis and ROS production. The information obtained gave new insight into chalcone derivatives with the potential to be developed as immunomodulators.

  7. Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents.

    Science.gov (United States)

    Luo, Wen; Wang, Ting; Hong, Chen; Yang, Ya-Chen; Chen, Ying; Cen, Juan; Xie, Song-Qiang; Wang, Chao-Jie

    2016-10-21

    A new series of 4-dimethylamine flavonoid derivatives were designed and synthesized as potential multifunctional anti-Alzheimer agents. The inhibition of cholinesterase activity, self-induced β-amyloid (Aβ) aggregation, and antioxidant activity by these derivatives was investigated. Most of the compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. A Lineweaver-Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. The derivatives showed potent self-induced Aβ aggregation inhibition and peroxyl radical absorbance activity. Moreover, compound 6d significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Thus, these compounds could become multifunctional agents for further development for the treatment of AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Synthesis and anticancer activity evaluation of some benzothiazole-piperazine derivatives.

    Science.gov (United States)

    Gurdal, Enise Ece; Buclulgan, Ebru; Durmaz, Irem; Cetin-Atalay, Rengul; Yarim, Mine

    2015-01-01

    Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Aroyl substituted compounds 1h and 1j were found to be the most active derivatives. In addition, further investigation of compounds 1h and 1j by Hoechst staining and FACS revealed that these compounds cause apoptosis by cell cycle arrest at subG1 phase.

  9. Characterization and Immunological Evaluation of Low-Molecular- Weight Alginate Derivatives.

    Science.gov (United States)

    Xu, Xu; Bi, Decheng; Wan, Min

    2016-01-01

    Alginate is a naturally occurring acidic linear polysaccharide obtained from marine brown seaweed. Low molecular weight structurally diverse derivatives and oligosaccharides derived from alginate have shown various tremendous biological and pharmacological activities. It has been demonstrated that immuno-inflammation is involved in many prevalent human diseases, such as cancer, severe infection and neurodegeneration. Given the activities of marine natural products in the regulation of immune responses, increasing efforts are being made toward the development of lowmolecular- weight natural compounds that aid in the prevention and treatment of immune- and inflammatory-related diseases. In this review, we describe the development of chemical modification and molecular depolymerization methods that modify the physicochemical and biological characteristics of alginate. Additionally, current progress in research on immuno-inflammatory, anti-neurodegenerative and anti-tumor activities of alginate derivatives is highlighted.

  10. The facile insertion of β-keto sulfones to arynes: The direct preparation of polysubstituted ortho-keto benzyl sulfones

    Institute of Scientific and Technical Information of China (English)

    Jian Xue; Lu Ling Wu; Xian Huang

    2008-01-01

    One novel carbon-carbon bond insertion reaction of arynes has been developed. By this reaction β-keto sulfones can insert the triple bond of arynes to prepare polysubstituted ortho-keto benzyl sulfones.

  11. Flight testing techniques for the evaluation of light aircraft stability derivatives: A review and analysis

    Science.gov (United States)

    Smetana, F. O.; Summery, D. C.; Johnson, W. D.

    1972-01-01

    Techniques quoted in the literature for the extraction of stability derivative information from flight test records are reviewed. A recent technique developed at NASA's Langley Research Center was regarded as the most productive yet developed. Results of tests of the sensitivity of this procedure to various types of data noise and to the accuracy of the estimated values of the derivatives are reported. Computer programs for providing these initial estimates are given. The literature review also includes a discussion of flight test measuring techniques, instrumentation, and piloting techniques.

  12. Synthesis and preliminary evaluation of the antimicrobial activity of selected 3-benzofurancarboxylic acid derivatives.

    Science.gov (United States)

    Kossakowski, Jerzy; Krawiecka, Mariola; Kuran, Bozena; Stefańska, Joanna; Wolska, Irena

    2010-07-06

    Halogen derivatives of selected 3-benzofurancarboxylic acids were prepared using 6-acetyl-5-hydroxy-2-methyl-3-benzofuranocarboxylic acid as starting material. (1)H-NMR spectra were obtained for all of the synthesized structures, and for compound VI, an X-ray crystal structure was also obtained. All derivatives were tested for antimicrobial activity against a selection of Gram-positive cocci, Gram-negative rods and yeasts. Three compounds, III, IV, and VI, showed antimicrobial activity against Gram-positive bacteria (MIC 50 to 200 microg/mL). Compounds VI and III exhibited antifungal activity against the Candida strains C. albicans and C. parapsilosis (MIC-100 microg/mL).

  13. Paraneoplastic Galactorrhea in Childhood T-ALL: An Evaluation of Tumor-derived Prolactin.

    Science.gov (United States)

    Grimes, Allison; Mirkheshti, Nooshin; Chatterjee, Bandana; Tomlinson, Gail; Assanasen, Chatchawin

    2017-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) comprises 15% of childhood leukemia. Although multiagent pulse chemotherapy has improved event-free survival in recent decades, the lack of reliable prognosticators and high rate of relapse remain a challenge. Described is a novel discovery of tumor-derived hyperprolactinemia in childhood T-ALL through a case associated with paraneoplastic galactorrhea. Prolactin production by tumor cells, although a rare phenomenon, is previously demonstrated in several adult cancers and 2 pediatric malignancies with unknown implications. This is the first report demonstrating tumor-derived prolactin in pediatric T-ALL and offers potential as a disease marker and therapeutic drug target.

  14. Immobilization of Zidovudine Derivatives on the SBA-15 Mesoporous Silica and Evaluation of Their Cytotoxic Activity.

    Science.gov (United States)

    Lewandowski, Dawid; Lewandowska, Marta; Ruszkowski, Piotr; Pińska, Anita; Schroeder, Grzegorz

    2015-01-01

    Novel zidovudine derivatives, able to be covalently conjugated to silica surface, have been obtained and grafted to SBA-15 mesoporous silica. Cytotoxic activity of the hybrid organic-inorganic (zidovudine derivatives-silica) systems against HeLa and KB cell lines has been analyzed. Addition of folic acid had a positive influence on the cytotoxicity. Up to 69% of HeLa and 65% of KB tumor cells growth inhibition has been achieved at low silica concentration used (10 μg/mL).

  15. 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

    as a new method where 10 mul of a spore suspension is placed in a spot on the test sample. The new method gave additional information about fungal growth on biologically derived materials, revealing a clear difference between survival and growth. PHB and PIA turned out to be most suitable for food......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...

  16. Design, synthesis, and evaluation of carnosine derivatives as selective and efficient sequestering agents of cytotoxic reactive carbonyl species.

    Science.gov (United States)

    Vistoli, Giulio; Orioli, Marica; Pedretti, Alessandro; Regazzoni, Luca; Canevotti, Renato; Negrisoli, Gianpaolo; Carini, Marina; Aldini, Giancarlo

    2009-06-01

    Carnosine aryl derivatives as sequestering agents of RCS: Reactive carbonyl species (RCS) are cytotoxic mediators representing a novel drug target, as they are presumed to play a pathogenic role in several diseases. Carnosine is a selective RCS-sequestering agent, but is rapidly hydrolyzed by serum carnosinase. Herein we describe the in silico design, synthesis, and evaluation of a set of carnosine aryl derivatives.Reactive carbonyl species (RCS) are important cytotoxic mediators generated by lipid oxidation of polyunsaturated fatty acids (PUFAs) and represent a novel drug target, as they are presumed to play a pathogenic role in several diseases. L-Carnosine (L-CAR, beta-alanyl-L-histidine) is a specific detoxifying agent of RCS, but is rapidly hydrolyzed in human serum by carnosinase, a specific dipeptidase. Herein we describe the in silico design, synthesis, and biological evaluation of carnosine derivatives that are resistant to carnosinase and that have increased quenching efficacy. Stability against carnosinase-mediated turnover was achieved by isomerization of the histidine residue, leading to D-carnosine (D-CAR, beta-alanyl-D-histidine), which maintains the same quenching activity of L-carnosine. A molecular modeling approach was then used to design derivatives characterized by an increased quenching efficacy. The most promising candidates were synthesized, and their stability and quenching activity were evaluated. This study describes a set of aryl derivatives that are characterized by high stability in human plasma and a quenching activity toward 4-hydroxy-trans-2-nonenal (HNE), chosen as a model of RCS, up to threefold greater than D-carnosine.

  17. Exploring the Phe-Gly Dipeptide-Derived Piperazinone Scaffold in the Search for Antagonists of the Thrombin Receptor PAR1

    Directory of Open Access Journals (Sweden)

    Ángel M. Valdivielso

    2014-04-01

    Full Text Available A series of Phe-Gly dipeptide-derived piperazinones containing an aromatic urea moiety and a basic amino acid has been synthesized and evaluated as inhibitors of human platelet aggregation induced by the PAR1 agonist SFLLRN and as cytotoxic agents in human cancer cells. The synthetic strategy involves coupling of a protected basic amino acid benzyl amide to 1,2- and 1,2,4-substituted-piperazinone derivatives, through a carbonylmethyl group at the N1-position, followed by formation of an aromatic urea at the exocyclic moiety linked at the C2 position of the piperazine ring and removal of protecting groups. None of the compounds showed activity in the biological evaluation.

  18. (2S,4S-3-Benzoyl-4-benzyl-2-tert-butyl-1,3-oxazolidin-5-one

    Directory of Open Access Journals (Sweden)

    Victoria J. Dungan

    2012-09-01

    Full Text Available In the title compound, C21H23NO3, the central oxazolidinone ring is approximately planar, the maximum deviation from the plane through the central ring being 0.043 (1 Å. The tert-butyl and benzyl substituents are cis to each other and trans to the N-benzoyl group. The interplanar angle between the aromatic rings of the C-benzyl and N-benzoyl groups is 81.10 (4°.

  19. A general strategy for organocatalytic activation of C-H bonds via photoredox catalysis: direct arylation of benzylic ethers.

    Science.gov (United States)

    Qvortrup, Katrine; Rankic, Danica A; MacMillan, David W C

    2014-01-15

    Direct C-H functionalization and arylation of benzyl ethers has been accomplished via photoredox organocatalysis. The productive merger of a thiol catalyst and a commercially available iridium photoredox catalyst in the presence of household light directly affords benzylic arylation products in good to excellent yield. The utility of this methodology is further demonstrated in direct arylation of 2,5-dihydrofuran to form a single regioisomer.

  20. 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.

  1. Novel pleuromutilin derivatives as antibacterial agents: synthesis, biological evaluation and molecular docking studies.

    Science.gov (United States)

    Wang, Xinyang; Ling, Yong; Wang, Hui; Yu, Jianghe; Tang, Junming; Zheng, Heng; Zhao, Xi; Wang, Donggeng; Chen, Guangtong; Qiu, Wenqian; Tao, Jinhua

    2012-10-01

    Owing to the increasingly serious problems caused by multidrug resistance in community-acquired infection pathogens, it has become an urgent need to develop new classes of antibiotics for overcoming the resistance. In this paper, we describe the design and synthesis of novel pleuromutilin derivatives containing the (2-aminothiazol-4-yl)-4-methyl group, as well as their in vitro antibacterial activities against Gram-positive clinical bacteria. Most of the tested compounds displayed strong antibacterial activities against these methicillin-susceptible and methicillin-resistant bacteria. Particularly noteworthy compound 15 and its derivative 16e, both showed potent antibacterial properties (0.0625-0.5μg/mL) that are superior to amoxicillin and tiamulin. Molecular docking studies suggested that the amino thiazole ring on the side chains of the pleuromutilin derivatives can in general be accommodated near the mutilin core in the binding pocket, and thus play an important role in the activity of the whole molecule. The findings reported herein may provide a new insight into the design of novel pleuromutilin derivatives for human clinical use. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Synthesis, physicochemical and biological evaluation of 2-amino-5-chlorobenzophenone derivatives as potent skeletal muscle relaxants

    Directory of Open Access Journals (Sweden)

    Rajesh K. Singh

    2015-05-01

    Full Text Available A series of novel 2-amino-5-chlorobenzophenone derivatives (3a–3g were prepared by the reaction of 2-(chloroacetamido-5-chlorobenzophenone and different aniline derivatives by both conventional and microwave methods and structures were confirmed on the basis of their TLC, IR, 1H NMR and CHN elemental studies. Out of the two methods, microwave methods was found to give better yield. All the synthesized compounds were subjected to physicochemical parameters determination for BBB penetration through online software. The logP values of most of our test compounds indicate that test compounds have the potential to be CNS active. The experimentally determined and calculated values of logP are very much similar to values of logP calculated by the online software chemsilico and are in the range required for good CNS activity. The values of other physicochemical parameters like molecular weight, nON value, nOHNH value, n-violations and the number of rotatable bonds of all the test compounds also lie between the ranges that are required for good BBB penetration. The compounds were screened for the skeletal muscle relaxant activity and from the investigation, it is quite apparent that all the 2-amino-5-chlorobenzophenone derivatives (3a–3g possess significant differences between control group and treated group, P < 0.001. Among these 2-amino-5-chlorobenzophenone derivatives, the compound bearing o-toluidine as a substituent (3e possesses the highest skeletal muscle relaxant activity.

  3. Evaluation of the antioxidant effects of four main theaflavin derivatives through chemiluminescence and DNA damage analyses

    Institute of Scientific and Technical Information of China (English)

    Yuan-yuan WU; Wei LI; Yi XU; En-hui JIN; You-ying TU

    2011-01-01

    Theaflavins (TFs) are the dimers of a couple of epimerized catechins,which are specially formed during black tea fermentation.To explore the differences among four main TF derivatives (theaflavin (TF1),theaflavin3-gallate (TF2A),theaflavin-3′-gallate (TF2B),and theaflavin-3,3′-digallate (TF3)) in scavenging reactive oxygen species (ROS) in vitro,their properties of inhibiting superoxide,singlet oxygen,hydrogen peroxide,and the hydroxyl radical,and their effects on hydroxyl radical-induced DNA oxidative damage were systematically analyzed in the present study.The results show that,compared with (-)-epigallocatechin gallate (EGCG),TF derivatives were good antioxidants for scavenging ROS and preventing the hydroxyl radical-induced DNA damage in vitro.TF3 was the most positive in scavenging hydrogen peroxide and hydroxyl radical,and TF1 suppressed superoxide.Positive antioxidant capacities of TF2B on singlet oxygen,hydrogen peroxide,hydroxyl radical,and the hydroxyl radical-induced DNA damage in vitro were found.The differences between the antioxidant capacities of four main TF derivatives in relation to their chemical structures were also discussed.We suggest that these activity differences among TF derivatives would be beneficial to scavenge different ROS with therapeutic potential.

  4. Synthesis and Evaluation of Selected Benzimidazole Derivatives as Potential Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Fatmah A. S. Alasmary

    2015-08-01

    Full Text Available A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA strains with minimum inhibitory concentrations (MICs comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl-1H-benzo[d]imidazole and (1H-benzo[d]imidazol-2-ylmethanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications.

  5. 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)

  6. Novel pyrazole and indazole derivatives: synthesis and evaluation of their anti-proliferative and anti-angiogenic activities

    OpenAIRE

    Tzanetou, Evangelia; Liekens, Sandra; Kasiotis, Konstantinos M.; Fokialakis, Nikolas; Haroutounian, Serkos A

    2012-01-01

    The synthesis of several new pyrazole and indazole derivatives from acetophenone and tetralone substrates is reported. The bioactivities of the new compounds were evaluated through in vitro assays for endothelial cell proliferation and tube formation. Results herein indicate that the easily prepared compounds containing the indazole structural framework exhibit potent cytostatic properties against all cell lines tested, with compounds 13 and 14 being the most active displaying IC(50) values o...

  7. Synthesis, Characterization and Biological Evaluation of Some Quinoxaline Derivatives: A Promising and Potent New Class of Antitumor and Antimicrobial Agents

    OpenAIRE

    Al-Marhabi, Aisha; Abbas, Hebat-Allah; Ammar, Yousry

    2015-01-01

    the present work deals with the synthesis of some novel tetrazolo[1,5-a]quinoxalines, N-pyrazoloquinoxalines, the corresponding Schiff bases, 1,2,4-triazinoquinoxalines and 1,2,4-triazoloquinoxalines. These compounds were synthesized via the reaction of the key intermediate hydrazinoquinoxalines with various reagents and evaluated for anticancer and antimicrobial activity. The results indicated that tetrazolo[1,5-a]quinoxaline derivatives showed the best result, with the highest inhibitory ef...

  8. 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)-.

  9. Synthesis and evaluation of novel prenylated chalcone derivatives as anti-leishmanial and anti-trypanosomal compounds.

    Science.gov (United States)

    Passalacqua, Thais Gaban; Dutra, Luiz Antonio; de Almeida, Letícia; Velásquez, Angela Maria Arenas; Torres, Fabio Aurelio Esteves; Yamasaki, Paulo Renato; dos Santos, Mariana Bastos; Regasini, Luis Octavio; Michels, Paul A M; Bolzani, Vanderlan da Silva; Graminha, Marcia A S

    2015-08-15

    Chalcones form a class of compounds that belong to the flavonoid family and are widely distributed in plants. Their simple structure and the ease of preparation make chalcones attractive scaffolds for the synthesis of a large number of derivatives enabling the evaluation of the effects of different functional groups on biological activities. In this Letter, we report the successful synthesis of a series of novel prenylated chalcones via Claisen-Schmidt condensation and the evaluation of their effect on the viability of the Trypanosomatidae parasites Leishmania amazonensis, Leishmania infantum and Trypanosoma cruzi.

  10. Flotation of kaolinite and diaspore with hexadecyl dimethyl benzyl ammonium chloride

    Institute of Scientific and Technical Information of China (English)

    HU Yue-hua; OUYANG Kui; CAO Xue-feng; ZHANG Li-min

    2008-01-01

    Tertiary amine was synthesized from fatty amine and formaldehyde. And then the synthesized tertiary amine was used toreact with benzyl chloride to synthesize hexadecyl dimethyl benzyl ammonium chloride (1627) at ambient pressure. Using thesynthesized 1627 as collector, the flotation properties of diaspore and kaolinite were investigated by single mineral and mixedmineral test. The flotation mechanism of diaspore, kaolinite and 1627 was discussed based on FTIR spectra. The results show that themass ratio of aluminum to silicate achieves 15.02 and the recovery of alumina in concentrate is 43.07% using 1627 as a collector. The 1627 is found to be a more effective and a promising collector for reverse flotation to remove aluminum-silicate minerals frombauxite.

  11. Structural micellar transition for fluorinated and hydrogenated sodium carboxylates induced by solubilization of benzyl alcohol.

    Science.gov (United States)

    González-Pérez, Alfredo; Ruso, Juan M; Prieto, Gerardo; Sarmiento, Félix

    2004-09-28

    The solubility of benzyl alcohol in micellar solutions of sodium octanoate and sodium perfluorooctanoate was studied. From the isotherms of specific conductivity versus molality at different alcohol concentrations, the critical micelle concentration and the degree of ionization of the micelles were determined. The cmc linearly decreases upon increasing the amount of benzyl alcohol present in aqueous solutions with two distinct slopes. This phenomenon was interpreted as a clustering of alcohol molecules above a critical point, around 0.1 mol kg(-1). Attending to the equivalent conductivity versus square root of molality, the presence of a second micellar structure for the fluorinated compound was assumed. The thermodynamic parameters associated with the process of micellization were estimated by applying Motomura's model for binary surfactant mixtures, modified by Pérez-Villar et al. (Colloid Polym. Sci 1990, 268, 965) for the case of alcohol-surfactant solutions. A comparison of the hydrogenated and fluorinated compounds was carried out and discussed.

  12. Comparison of ivermectin and benzyl benzoate lotion for scabies in Nigerian patients.

    Science.gov (United States)

    Sule, Halima M; Thacher, Tom D

    2007-02-01

    Few studies have compared ivermectin directly with topical agents in developing countries. We compared the effectiveness of oral ivermectin (200 microg/kg) with topical 25% benzyl benzoate and monosulfiram soap in 210 subjects of age 5 to 65 years with scabies. Subjects with persistent lesions after 2 weeks received a second course of treatment. All lesions had resolved after 2 weeks in 77 of 98 (79%) subjects treated with ivermectin and in 60 of 102 (59%) subjects treated topically (P = 0.003). The improvement in severity score was greater in the ivermectin group than in the topical treatment group (P topical treatment group (P = 0.04). Compared with topical benzyl benzoate and monosulfiram in the treatment of scabies, ivermectin was at least as effective and led to more rapid improvement.

  13. Crystal structure of O-benzyl-l-tyrosine N-carb-oxy anhydride.

    Science.gov (United States)

    Inada, Aya; Kanazawa, Hitoshi

    2017-04-01

    In the title compound, C17H15NO4 (alternative name; O-benzyl-l-tyrosine N-carb-oxy anhydride), the oxazolidine ring is planer, with an r.m.s. deviation of 0.039 Å. The benz-yloxy and benzyl rings are almost coplanar, making a dihedral angle of 0.078 (10)°, and are inclined to the oxazolidine ring by 59.16 (11) and 58.42 (11)°, respectively. In the crystal, mol-ecules are linked by N-H⋯O and C-H⋯O hydrogen bonds, forming ribbons propagating along [010]. The ribbons are linked by C-H⋯π inter-actions, forming a three-dimensional supra-molecular structure. The oxazolidine rings of adjacent ribbons are arranged into a layer parallel to the ab plane. This arrangement is favourable for the polymerization of the compound in the solid state.

  14. Crystal structure of β-benzyl dl-aspartate N-carb-oxyanhydride.

    Science.gov (United States)

    Kanazawa, Hitoshi; Inada, Aya

    2017-03-01

    In the title racemic compound, C12H11NO5 [systematic name: benzyl 2-(2,5-dioxooxazolidin-4-yl)acetate], the oxazolidine ring is planar, with an r.m.s. deviation of 0.03 Å. The benzyl ring is almost normal to the oxazolidine ring, making a dihedral angle of 80.11 (12)°. In the crystal, inversion dimers are formed between the l- and d-enanti-omers via pairs of N-H⋯O hydrogen bonds. This arrangement is favourable for the polymerization of the compound in the solid state. The dimers are linked by C-H⋯O hydrogen bonds, forming layers parallel to the ab plane.

  15. Enantioselective, intermolecular benzylic C-H amination catalysed by an engineered iron-haem enzyme

    Science.gov (United States)

    Prier, Christopher K.; Zhang, Ruijie K.; Buller, Andrew R.; Brinkmann-Chen, Sabine; Arnold, Frances H.

    2017-07-01

    C-H bonds are ubiquitous structural units of organic molecules. Although these bonds are generally considered to be chemically inert, the recent emergence of methods for C-H functionalization promises to transform the way synthetic chemistry is performed. The intermolecular amination of C-H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist. Here we report the directed evolution of an iron-containing enzymatic catalyst—based on a cytochrome P450 monooxygenase—for the highly enantioselective intermolecular amination of benzylic C-H bonds. The biocatalyst is capable of up to 1,300 turnovers, exhibits excellent enantioselectivities, and provides access to valuable benzylic amines. Iron complexes are generally poor catalysts for C-H amination: in this catalyst, the enzyme's protein framework confers activity on an otherwise unreactive iron-haem cofactor.

  16. Evaluation of Calcarea carbonica derivative complex (M8 on milk parameters in the dairy cow

    Directory of Open Access Journals (Sweden)

    Daniel Ollhoff

    2012-09-01

    Full Text Available Background Any dairy herd that continually has a somatic cell count (SCC above 200,000 cells/ml has an indication of mammary gland inflammation (mastitis. Routine use of antibiotics to prevent mastitis is prohibited by organic farming regulations. This limitation has lead researchers to focus on cows natural defense mechanisms [1]. Calcarea carbonica derivative complex (M8 is a complex high diluted medication comprised of comprised of Calcarea carbonica 16x, Aconitum napellus 20x, Arsenicum album 18x, Asa foetida 20x, Conium maculatum 17x, Ipecacuanha 13x, Phosphorus 20x, Rhus toxicodendron 17x, Silicea 20x, Sulphur 24x, and Thuya occidentalis 19x. Dilution procedures have followed standard methodology described at the Brazilian Homeopathic Pharmacopoeia. This medication has enhanced immune system responses both in vitro and in vivo in a murine model [2]. Aims In the present study, we investigate the response of dairy cows after M8 treatment. Methodology The study was performed as a randomized, observer double-blinded and placebo-controlled trial, with a stratified design, using lactation number and SCC as stratification factors. The study sample consisted of 42 lactating dairy cows (Holstein in one high producing dairy herd with 52 cows in milk in southern Brazil, divided into two experimental groups (n=21. Exclusion criteria were cows with clinical mastitis or receiving any other medical treatment. Pre- and post-milking teat disinfection was practiced in the herd. All cows were clinically examined, with udder and milk samples being appraised according to Rosenberger (1990 [3]. During 3 months one group received daily M8 treatment, the other placebo. Oral administration of 5 ml/day/cow was performed using an automatic dosage dispenser. Monthly, milk production, SCC, fat and total protein content were carefully recorded for each animal by an official milk recording program. SCC were log transformed for analysis. ANOVA and Tukey test were

  17. Benzyl 2-β-Glucopyranosyloxybenzoate, a New Phenolic Acid Glycoside from Sarcandra glabra

    OpenAIRE

    Xudong Xu; Haifeng Wu; Xiaoru Hu; Shilin Chen; Junshan Yang; Xiaopo Zhang

    2012-01-01

    From the whole plant of Sarcandra glabra, a new phenolic acid glycoside, benzyl 2-β-glucopyranosyloxybenzoate (1), together with seven known compounds including eleutheroside B1 (2), 5-O-caffeoylshikimic acid (3), (–)-(7S, 8R)-dihydrodehydro-diconiferyl alcohol (

  18. Lipase-catalysed selective deacetylation of phenolic/enolic acetoxy groups in peracetylated benzyl phenyl ketones.

    Science.gov (United States)

    Parmar, V S; Pati, H N; Azim, A; Kumar, R; Himanshu; Bisht, K S; Prasad, A K; Errington, W

    1998-01-01

    Highly chemo- and regioselective de-esterification has been observed in the deacetylation of peracetylated enolic forms of polyphenolic benzyl phenyl ketones by lipase from porcine pancreas (PPL) suspended in tetrahydrofuran (THF). The enzyme selectively deacetylates the enolic acetoxy over the phenolic acetoxy group(s) and continuation of the reaction resulted, in addition the regioselective deacetylation of acetoxy function para to the nuclear carbonyl group.

  19. Crystal-phase control of molybdenum carbide nanobelts for dehydrogenation of benzyl alcohol.

    Science.gov (United States)

    Li, Zhongcheng; Chen, Chunhui; Zhan, Ensheng; Ta, Na; Li, Yong; Shen, Wenjie

    2014-05-04

    Belt-shaped molybdenum carbides in α- and β-phases were synthesized by reducing and carburizing a nano-sized α-MoO3 precursor with hydrocarbon-hydrogen mixtures at appropriate temperatures; the β-Mo2C nanobelts with a higher fraction of coordinatively unsaturated Mo sites were more active than the α-MoC1-x nanobelts in dehydrogenation of benzyl alcohol to benzaldehyde.

  20. Linear free energy relationship in reactions between diphenyl amine and benzyl bromides

    Indian Academy of Sciences (India)

    S Ranga Reddy; P Manikyamba

    2006-05-01

    Rate of reaction between benzyl bromide and diphenyl amine is retarded by electron-donating groups and enhanced by electron-withdrawing groups present on the benzene ring of the substrate. Hammett's reaction constant of the reaction decreases with increase in temperature according to the equation, \\rho = -11.92 + 3.54/ T. Minimal structural effects observed are attributed to the fact that the isokinetic temperature of the reaction is close to the reaction temperature.