Potential role of retinoids in ovarian physiology and pathogenesis of polycystic ovary syndrome.

Science.gov (United States)

Jiang, Yanwen; Li, Chunjin; Chen, Lu; Wang, Fengge; Zhou, Xu

2017-06-01

Retinoids (retinol and its derivatives) are required for maintaining vision, immunity, barrier function, reproduction, embryogenesis, cell proliferation and differentiation. Furthermore, retinoid signaling plays a key role in initiating meiosis of germ cells of the mammalian fetal ovary. Recently, studies indicated that precise retinoid level regulation in the ovary provides a molecular control of ovarian development, steroidogenesis and oocyte maturation. Besides, abnormal retinoid signaling may be involved in the pathogenesis of polycystic ovary syndrome (PCOS), one of the most common ovarian endocrinopathies in reproductive-aged women worldwide. This review primarily summarizes recent advancements made in investigating the action of retinoid signaling in ovarian physiology as well as the abnormal retinoid signaling in PCOS. Copyright © 2017. Published by Elsevier B.V.

Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders

NARCIS (Netherlands)

Qi, Xin-Rui; Zhao, Juan; Liu, Ji; Fang, Hui; Swaab, Dick F; Zhou, Jiang-Ning

The prefrontal cortex shows structural and functional alterations in mood disorders. Retinoid signaling, brain-derived neurotrophic factor (BDNF), and its receptor TrkB are reported to be involved in depression. Here, we found that mRNA levels of key elements of retinoid signaling were significantly

Photodecomposition and Phototoxicity of Natural Retinoids

Directory of Open Access Journals (Sweden)

Peter P. Fu

2005-04-01

Full Text Available Sunlight is a known human carcinogen. Many cosmetics contain retinoid-based compounds, such as retinyl palmitate (RP, either to protect the skin or to stimulate skin responses that will correct skin damaged by sunlight. However, little is known about the photodecomposition of some retinoids and the toxicity of these retinoids and their sunlight-induced photodecomposition products on skin. Thus, studies are required to test whether topical application of retinoids enhances the phototoxicity and photocarcinogenicity of sunlight and UV light. Mechanistic studies are needed to provide insight into the disposition of retinoids in vitro and on the skin, and to test thoroughly whether genotoxic damage by UV-induced radicals may participate in any toxicity of topically applied retinoids in the presence of UV light. This paper reports the update information and our experimental results on photostability, photoreactions, and phototoxicity of the natural retinoids including retinol (ROH, retinal, retinoid acid (RA, retinyl acetate, and RP (Figure 1.

Changes in the skeleton after long-term treatment with retinoids

Energy Technology Data Exchange (ETDEWEB)

Montag, M.; Reiser, M.; Hamm, H.; Traupe, H.; Vogt, H.J.

1988-07-01

The synthetic retinoids, the vitamin-A-derivatives ethretinate and isotretinoin, have substantially enlarged the therapeutic arsenal in dermatology. They are primarily used in severe cases of acne and cornification disorders. In the majority of cases, long-term treatment is necessary. Certain side effects in the skeletal system can occur, e.g., osteoporosis, premature epiphyseal closure, and changes similar to DISH (diffuse idiopathic skeletal hyperostosis). We discuss the reports in the literature and our own observations in 31 patients treated at the Westphalian Wilhelms University in Muenster, as well as at the Technical University in Munich. In 3 out of 31 patients treated by retinoids on a long-term basis, skeletal changes were found radiologically as a result of the retinoid medication.

Photo-fragmentation behavior of methyl- and methoxy-substituted derivatives of hexa-peri-hexabenzocoronene (HBC) cations

Science.gov (United States)

Zhen, Junfeng; Castellanos, Pablo; Linnartz, Harold; Tielens, Alexander G. G. M.

2016-11-01

A systematic study, using ion trap time-of-flight mass spectrometry, is presented for the photo-fragmentation of methyl- and methoxy-substituted derivatives of HBC cations, (OCH3)6HBC+ and (CH3)4(OCH3)2HBC+. Both substituted HBC cations fragment through sequential loss of CH3CO units upon laser (595nm) irradiation, resulting in a PAH-like derivative C36H12+ and a methyl-substituted PAH derivative C44H24+ , respectively. Upon ongoing irradiation, these species further fragment. For lower laser energy C44H24+ dehydrogenates and photo-fragments through CH3 and CHCH2 unit losses; for higher laser energy isomerization takes place, yielding a regular PAH-like configuration, and both stepwise dehydrogenation and C2/C2H2 loss pathways are found. C36H12+ follows largely this latter fragmentation scheme upon irradiation. It is concluded that the photo-dissociation mechanism of the substituted PAH cations studied here is site selective in the substituted subunit. This work also shows experimental evidence that photo-fragmentation of substituted PAHs may contribute to the formation in space of smaller species that are normally considered to form by merging atoms and molecules.

Cis-retinoids and the chemistry of vision.

Science.gov (United States)

Cascella, Michele; Bärfuss, Simon; Stocker, Achim

2013-11-15

We discuss here principal biochemical transformations of retinoid molecules in the visual cycle. We focus our analysis on the accumulating evidence of alternate pathways and functional redundancies in the cycle. The efficiency of the visual cycle depends, on one hand, on fast regeneration of the photo-bleached chromophores. On the other hand, it is crucial that the cyclic process should be highly selective to avoid accumulation of byproducts. The state-of-the-art knowledge indicates that single enzymatically active components of the cycle are not strictly selective and may require chaperones to enhance their rates. It appears that protein-protein interactions significantly improve the biological stability of the visual cycle. In particular, synthesis of thermodynamically less stable 11-cis-retinoid conformers is favored by physical interactions of the isomerases present in the retina with cellular retinaldehyde binding protein. Copyright © 2013 Elsevier Inc. All rights reserved.

Synthesis and solar-cell applications of novel furanyl-substituted anthracene derivatives

Science.gov (United States)

Kivrak, Arif; Er, Ömer Faruk; Kivrak, Hilal; Topal, Yasemin; Kuş, Mahmut; Çamlısoy, Yesim

2017-11-01

At present, novel furanyl-substituted anthracene derivatives; namely 9,10-di(furan-2-yl)anthracene (DFA), 5,5‧-(anthracene-9,10-diyl)bis(furan-2-carbaldehyde) (DAFA) and 2,2‧-((5,5‧-(anthracene-9,10-diyl)bis(furan-5,2-diyl))bis(methanylylidene))dimalononitrile (DCNFA) were designed and synthesized successfully by employing Stille Cross-Coupling, Vilsmeier-Haack and Knoevenagel condensation reactions, respectively. This methodology provides a practical new route for the synthesis of furanyl-substituted anthracene derivatives bearing strong electron-withdrawing groups. The electrochemical and electro-optical properties of these novel furanyl-substituted anthracene derivatives were also examined with strong acceptor-π-donor-π-acceptor interactions. Furthermore, Highest occupied molecular orbital (HOMO), Lowest Unoccupied molecular orbital (LUMO), and band gap (Eg) values were investigated by using spectroscopic methods. Electrochemical and electro-optical properties were calculated and compared to DFA, DAFA and DCNFA. Eg was found as 2.85, 2.71, and 2.33 eV, respectively. Consequently, Organic Solar Cells (OSC) were fabricated to investigate their solar cell performances. The strong electron withdrawing groups did not increase the solar cell performance of furanyl-anthracenes. Surprisingly, DFA was found to exhibit the best OSCs performance (Efficiency = 3.36). As a result, one could note that these novel furanyl-substituted anthracene derivatives are good candidate for the applications of the OSCs. Our results might help in the development of new materials with important electrochemical functions by giving the advantage of designing and further derivatization of new generation small organic molecules for photovoltaic device applications.

Photophysical investigation of cyano-substituted terrylenediimide derivatives.

Science.gov (United States)

Kennes, Koen; Baeten, Yannick; Vosch, Tom; Sempels, Wouter; Yordanov, Stoyan; Stappert, Sebastian; Chen, Long; Müllen, Klaus; Hofkens, Johan; Van der Auweraer, Mark; Fron, Eduard

2014-12-18

Two new terrylenediimide (TDI) chromophores with cyano substituents in the bay and core area (BCN-TDI and OCN-TDI, respectively) have been characterized by a wide range of techniques, and their applicability for stimulated emission depletion (STED) microscopy has been tested. By cyano substitution an increase of the fluorescence quantum yield and a decrease of the nonradiative rate constant is achieved and attributed to a reduced charge-transfer character of the excited state due to a lower electron density of the TDI core. For BCN-TDI, the substitution in the bay area induces a strong torsional twist in the molecule which, similar to phenoxy bay-perylenediimide (PDI), has a strong effect on the fluorescence lifetime but appears to prevent the aggregation that is observed for OCN-TDI. The single-molecule photobleaching stability of BCN- and OCN-TDI is lower than that of a reference TDI without cyano substitution (C7-TDI), although less so for OCN-TDI. The photophysical properties of the excited singlet state are only slightly influenced by the cyano groups. The observed intense stimulated emission, the pump-dump-probe experiments, and STED single-molecule imaging indicate that STED experiments with the cyano-substituted TDIs are possible. However, because of aggregation and more efficient photobleaching, the performance of BCN- and OCN-TDI is worse than that of the reference compound without cyano groups (C7-TDI). Bay-substituted TDIs are less suitable for STED microscopy.

Quantitation of biological retinoids by high-pressure liquid chromatography: primary internal standardization using tritiated retinoids

International Nuclear Information System (INIS)

Cullum, M.E.; Zile, M.H.

1986-01-01

A single method is described for quantitation of 14 retinoids found in biological material. The method consists of reversed-phase HPLC, internal standardization, and carrier extraction procedures with three synthetic retinoids. Primary standardization of HPLC uv detector is achieved using tritiated all-trans-retinoic acid, all-trans-retinol, all-trans-retinyl palmitate, and all-trans-retinyl acetate. Extraction methods are standardized by correlating the uv absorbance of retinoids at 340 nm with radioactivity of tritiated retinoids of known specific activity. Quantitation of 10 pg of tritiated or 5 ng of nonradioactive retinoid per 0.1 g sample in a polarity range from 4-oxo-retinoic acid to retinyl stearate can be achieved in a single, 50-min chromatographic run. A single HPLC pump, a C 18 reversed-phased analytical column, a multistep three-solvent gradient, and inexpensive solvents based on methanol, water, and chloroform comprise this cost-effective chromatographic system. Our primary standardization method allows investigators employing different procedures to compare results between laboratories by standardizing the HPLC uv detector with commercially available tritiated retinoids. With this method we were able to quantitate nanomolar amounts of endogenous retinoic acids and retinyl esters, that HPLC uv only conditions usually would not detect in the circulation and liver of rats under physiological conditions

Molecular Recognition of Vesicles : Host-Guest Interactions Combined with Specific Dimerization of Zwitterions

NARCIS (Netherlands)

Voskuhl, Jens; Fenske, Tassilo; Stuart, Marc C. A.; Wibbeling, Birgit; Schmuck, Carsten; Ravoo, Bart Jan

2010-01-01

The aggregation of beta-cyclodextrin vesicles can be induced by an adamantyl-substituted zwitterionic guanidiniocarbonylpyrrole carboxylate guest molecule (1). Upon addition of 1 to the cyclodextrin vesicles at neutral pH, the vesicles aggregate (but do not fuse), as shown by using UV/Vis and

Influence of substitution on the proton donor and proton acceptor abilities of molecules. III. Study of chlorine and ftorine substitution alcohol

International Nuclear Information System (INIS)

Nurulloev, M.; Narziev, B.N.; Islomov, Z.; Fayzieva, M.

2006-01-01

This work gives the study of influence of chlorine and ftorine atoms as substitutions to proton donor and proton acceptor ability of primary, secondary and tertiary alifatic alcohol. In accordance to developed method the proton donor ability of studied substances are determined. It is shown that the quantity of proton donor ability of reactionary center of the molecules depend on substitution nature and its proton acceptor quantity. Proposed that substitution influence of these molecule mainly transferred by inductive effect

Retinoid Signaling in Pancreatic Cancer, Injury and Regeneration

Science.gov (United States)

Colvin, Emily K.; Susanto, Johana M.; Kench, James G.; Ong, Vivienna N.; Mawson, Amanda; Pinese, Mark; Chang, David K.; Rooman, Ilse; O'Toole, Sandra A.; Segara, Davendra; Musgrove, Elizabeth A.; Sutherland, Robert L.; Apte, Minoti V.; Scarlett, Christopher J.; Biankin, Andrew V.

2011-01-01

Background Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. Methodology/Principal Findings We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1), a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A). However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. Conclusions/Significance In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1. PMID:22220202

Retinoid signaling in pancreatic cancer, injury and regeneration.

Directory of Open Access Journals (Sweden)

Emily K Colvin

Full Text Available BACKGROUND: Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC. These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1, a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A. However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. CONCLUSIONS/SIGNIFICANCE: In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1.

High-throughput screening (HTS) and modeling of the retinoid ...

Science.gov (United States)

Presentation at the Retinoids Review 2nd workshop in Brussels, Belgium on the application of high throughput screening and model to the retinoid system Presentation at the Retinoids Review 2nd workshop in Brussels, Belgium on the application of high throughput screening and model to the retinoid system

"CH"/N substituted mer-Gaq3 and mer-Alq3 derivatives: an effective approach for the tuning of emitting color.

Science.gov (United States)

Gahungu, Godefroid; Zhang, Jingping

2005-09-22

Equilibrium geometry configurations of the "CH"/N substituted Alq3 and Gaq3 derivatives are calculated by density functional theory (B3LYP/6-31G). The frontier molecular orbital and gap energy calculations for all complexes have been performed at the HF/6-31G level. It was shown that, compared to the pristine molecules, the HOMO and LUMO are stabilized, the net effect being however an increasing/decreasing of the gap (Eg) depending on the position of the substituted group. On the basis of the equilibrium geometries, the effect of the substitution on the absorption and emission spectra was evaluated using TDB3LYP/3-21G. It was shown that the change of "CH"/N substituted position on 8-hydroxyquinoline ligand is a powerful approach for the tuning of emitting color. An important blue shift was predicted for 5-substituted 8-hydroxyquinoline derivatives, an important red one being observed for 4-substituted ones. Interestingly, relatively significant blue and red shifts were also predicted for the 7- and 2-substituted derivatives. In this work, the correlation between the spectrum shifts and the metal-ligand bonding is also discussed.

Banana-shaped molecules derived from substituted isophthalic acids

Indian Academy of Sciences (India)

Different precursors inducing the bending angle of the banana-shaped molecules. Figure 2. ... Pramana – J. Phys., Vol. 61, No. 2, August ... isotropic liquid; N: nematic; SmA: smectic A; SmC: smectic C. For other phase assign- ments, see text.

Potential radiosensitizing agents. 5. 2-Substituted benzimidazole derivatives

International Nuclear Information System (INIS)

Gupta, R.P.; Larroquette, C.A.; Agrawal, K.C.

1982-01-01

A series of 2-substituted benzimidazoles and their derivatives have been synthesized and tested for their ability to selectively sensitize hypoxic Chinese hamster cells (V-79) toward the lethal effect of ionizing radiation. These compounds were prepared by reacting the 2-substituted benzimidazoles with 1,2-epoxy-3-methoxypropane in the presence of potassium carbonate. Reaction of the 2-nitro and 2-methylfonyl analogue with the epoxide also yielded a cyclized material, which was confirmed to be a benzimidazo[2,1-b]oxazole. In an attempt to increase the electron affinity, 5- or 6-nitro-2-substituted-benzimidazoles were also synthesized and then reacted with the epoxide to yield the corresponding 1-substituted derivatives. The results of the biological tests for the radiosensitizing activity of these agents against Chinese hamster cells (V-79) in culture indicated that the 2-nitro-substituted analogues were the most effective sensitizers in this series

Srtucture and properties of intracomplexes of 2-substituted 8-mercaptoquinoline derivatives

International Nuclear Information System (INIS)

Sturis, A.P.; Bankovskij, Yu.A.; Pech, L.Ya.

1990-01-01

The results of investigation of the molecular and crystal structure of 2-substituted 8-mercaptoquinoline internal complexes (in particular complexes of cadmium and indium) have been reviewed. Substitution of hydrogen atom in o-position in relation to the nitrogen atom in the ligand molecule causes the steric hindrance in the molecules of complexes. Due to it the changes in structure of the central atom coordination center in the MR 2 complexes from the planar (8-mercaptoquinolinates) to the distored tetrahedral (2-substituted 8-mercaptoquinolinates) occur. The ascertainment of such effect allows to explain the changes in physicochemical properties of 2-substituted 8-mercaptoquinolinates (hypsochromic shift of absorption maxima, decrease of the amount of ligands connected to the central atom, decrease of stability, increase of solubility in organic solvents) in comparison with 8-mercaptoquinolinates

Studies of muonium-substituted molecules in 2-propanone and in aqueous solutions of 2-propanone

International Nuclear Information System (INIS)

Cox, S.F.J.; Renzi, R. De; Scott, C.A.; Hill, A.; Symons, M.C.R.; Bucci, C.; Vecli, A.

1984-04-01

The paper deals with muonium substituted molecules, which are formed when positive muons are implanted in pure 2-propanone and in binary aqueous systems; and are studied by the muon spin rotation technique. Studies of muonium substituted molecules are discussed under five topic headings: hyperfine interaction, influence of the solvent, radical formation, diamagnetic fraction and linewidths. (U.K.)

Signalling with retinoids in the human lung: validation of new tools for the expression study of retinoid receptors

International Nuclear Information System (INIS)

Poulain, Stéphane; Lacomme, Stéphanie; Battaglia-Hsu, Shyue-Fang; Manoir, Stanislas du; Brochin, Lydia; Vignaud, Jean-Michel; Martinet, Nadine

2009-01-01

Retinoid Receptors are involved in development and cell homeostasis. Alterations of their expressions have been observed in lung cancer. However, retinoid chemoprevention trials in populations at risk to develop such tumors have failed. Therefore, the pertinence of new clinical trials using second generation retinoid requires prior better understanding of retinoid signalling. This is our aim when validating extensively research tools, focused on Retinoic Acid Receptor beta, whose major role in lung cancer is documented. Biocomputing was used to assess the genomic organization of RAR beta. Its putative RAR-beta1' promoter features were investigated experimentally. Specific measures realized, with qRT-PCR Syber Green assays and a triplex of Taqman probes, were extensively validated to establish Retinoid Receptors mRNAs reference values for in vivo normal human bronchial cells, lung tumors and cell lines. Finally, a pan-RAR-beta antibody was generated and extensively validated by western-blot and immunoprecipitation. No promoter-like activity was found for RAR-beta1'. RAR-beta2 mRNAs increase signs the normal differentiation of the human bronchial epithelium while a decrease is observed in most lung cancer cell lines. Accordingly, it is also, along with RXR beta, down-regulated in lung tumors. When using nuclear extracts of BEAS-2B and normal lung cells, only the RAR-beta2 long protein isoform was recognized by our antibody. Rigorous samples processing and extensive biocomputing, were the key factors for this study. mRNA reference values and validated tools can now be used to advance researches on retinoid signalling in the lung

Hepatic retinoid levels in seven fish species (teleosts) from a tropical coastal lagoon receiving effluents from iron-ore mining and processing.

Science.gov (United States)

Pereira, Adriana A; van Hattum, Bert; Brouwer, Abraham

2012-02-01

The present study was undertaken to investigate the possible effects of Fe and trace element exposure on hepatic levels of retinoids in seven fish species. Concentrations of retinoids were measured in fish collected from a coastal lagoon in Brazil that receives effluents from an iron-ore mining and processing plant. Fish from nearby coastal lagoons were also included to assess possible differences related to chemical exposure. Results indicated considerable differences in hepatic retinoid composition among the various species investigated. The most striking differences were in retinol and derivative-specific profiles and in didehydro retinol and derivative-specific profiles. The Perciformes species Geophagus brasiliensis, Tilapia rendalli, Mugil liza, and Cichla ocellaris and the Characiforme Hoplias malabaricus were characterized as retinol and derivative-specific, while the Siluriformes species Hoplosternum littorale and Rhamdia quelen were didehydro retinol and derivative-specific fish species. A negative association was observed between Al, Pb, As, and Cd and hepatic didehydro retinoid levels. Fish with higher levels of hepatic Fe, Cu, and Zn showed unexpectedly significant positive correlations with increased hepatic retinol levels. This finding, associated with the positive relationships between retinol and retinyl palmitate with lipid peroxidation, may suggest that vitamin A is mobilized from other tissues to increase hepatic antioxidant levels for protection against oxidative damage. These data show significant but dissimilar associations between trace element exposure and hepatic retinoid levels in fish species exposed to iron-ore mining and processing effluents, without apparent major impacts on fish health and condition. Copyright © 2011 SETAC.

Topical retinoids in the management of photodamaged skin: from theory to evidence-based practical approach.

Science.gov (United States)

Darlenski, R; Surber, C; Fluhr, J W

2010-12-01

Skin, being exposed directly to the environment, represents a unique model for demonstrating the synergistic effects of intrinsic and extrinsic factors on the ageing process. Ultraviolet radiation (UVR) is the major factor among exogenous stressors responsible for premature skin ageing. The problem of skin ageing has captured public attention and has an important social impact. Different therapeutic approaches have been developed to treat cutaneous ageing and to diminish or prevent the negative effects of UVR. Topical retinoids represent an important and powerful class of molecules in the dermatologist's hands for the treatment of photodamaged skin. Since their introduction more than 20 years ago, topical retinoids have shown beneficial efficacy and good safety profiles in the management of photodamaged skin, and as therapeutic anti-ageing agents. This review provides a brief retrospective of the development of topical retinoids in the treatment of photodamaged skin, elucidates their mechanism of action, delineates their use and addresses clinical, pharmaceutical and regulatory issues in connection with their intended use. © 2010 The Authors. BJD © 2010 British Association of Dermatologists.

Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

International Nuclear Information System (INIS)

Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J.; Bridges, Lance C.

2014-01-01

Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH) 2 D 3 , a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion

Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

Energy Technology Data Exchange (ETDEWEB)

Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J. [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); Bridges, Lance C., E-mail: bridgesl@ecu.edu [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); East Carolina Diabetes and Obesity Institute, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States)

2014-11-28

Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH){sub 2}D{sub 3}, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion.

Chromosomal locations and modes of action of genes of the retinoid (vitamin A) system support their involvement in the etiology of schizophrenia

Energy Technology Data Exchange (ETDEWEB)

Goodman, A.B. [Columbia Univ. School of Public Health, New York, NY (United States)

1995-08-14

Vitamin A (retinoid), an essential nutrient for fetal and subsequent mammalian development, is involved in gene expression, cell differentiation, proliferation, migration, and death. Retinoic acid (RA) the morphogenic derivative of vitamin A is highly teratogenic. In humans retinoid excess or deficit can result in brain anomalies and psychosis. This review discusses chromosomal loci of genes that control the retinoid cascade in relation to some candidate genes in schizophrenia. The paper relates the knowledge about the transport, delivery, and action of retinoids to what is presently known about the pathology of schizophrenia, with particular reference to the dopamine hypothesis, neurotransmitters, the glutamate hypothesis, neurotransmitters, the glutamate hypothesis, retinitis pigmentosa, dermatologic disorders, and craniofacial anomalies. 201 refs., 1 tab.

Retinoid quantification by HPLC/MS(n)

Science.gov (United States)

McCaffery, Peter; Evans, James; Koul, Omanand; Volpert, Amy; Reid, Kevin; Ullman, M. David

2002-01-01

Retinoic acid (RA) mediates most of the biological effects of vitamin A that are essential for vertebrate survival. It acts through binding to receptors that belong to the nuclear receptor transcription factor superfamily (Mangelsdorf et al. 1994). It is also a highly potent vertebrate teratogen. To determine the function and effects of endogenous and exogenous RA, it is important to have a highly specific, sensitive, accurate, and precise analytical procedure. Current analyses of RA and other retinoids are labor intensive, of poor sensitivity, have limited specificity, or require compatibility with RA reporter cell lines (Chen et al. 1995. BIOCHEM: Pharmacol. 50: 1257-1264; Creech Kraft et al. 1994. BIOCHEM: J. 301: 111-119; Lanvers et al. 1996. J. Chromatogr. B Biomed. Appl. 685: 233-240; Maden et al. 1998. DEVELOPMENT: 125: 4133-4144; Wagner et al. 1992. DEVELOPMENT: 116: 55-66). This paper describes an HPLC/mass spectrometry/mass spectrometry product ion scan (HPLC/MS(n)) procedure for the analysis of retinoids that employs atmospheric pressure chemical ionization MS. The retinoids are separated by normal-phase column chromatography with a linear hexane-isopropanol-dioxane gradient. Each retinoid is detected by a unique series of MS(n) functions set at optimal collision-induced dissociation energy (30% to 32%) for all MS(n) steps. The scan events are divided into three segments, based on HPLC elution order, to maximize the mass spectrometer duty cycle. The all-trans, 9-cis, and 13-cis RA isomers are separated, if desired, by an isocratic hexane-dioxane-isopropanol mobile phase. This paper describes an HPLC/MS(n) procedure possessing high sensitivity and specificity for retinoids.

Mefloquine use, psychosis, and violence: a retinoid toxicity hypothesis.

Science.gov (United States)

Mawson, Anthony

2013-07-15

Mefloquine use has been linked to severe gastrointestinal and neuropsychiatric adverse effects, including cognitive disturbances, anxiety, depression, psychosis, and violence. The adverse effects of the drug are thought to result from the secondary consequences of hepatocellular injury; in fact, mefloquine is known to cause a transient, anicteric chemical hepatitis. However, the mechanism of mefloquine-associated liver damage and the associated neuropsychiatric and behavioral effects of the drug are not well understood. Mefloquine and other 8-amino-quinolines are the only antimalarial drugs that target the liver-stage malaria parasites, which selectively absorb vitamin A from the host. Vitamin A is also stored mainly in the liver, in potentially poisonous concentrations. These observations suggest that both the therapeutic effectiveness of mefloquine and its adverse effects are related to the ability of the 8-aminoquinolines to alter the metabolism of retinoids (vitamin A and its congeners). Several lines of evidence support the hypothesis that mefloquine neurotoxicity and other adverse effects reflect an endogenous form of hypervitaminosis A due to a process involving: mefloquine-induced dehydrogenase inhibition; the accumulation of retinoids in the liver; retinoid-induced hepatocellular damage; the spillage of stored retinoids into the circulation; and the transport of these compounds to the gut and brain in toxic concentrations. The retinoid hypothesis could be tested clinically by comparing cases of mefloquine toxicity and untreated controls in terms of retinoid profiles (retinol, retinyl esters, percent retinyl esters, and retinoic acid). Subject to such tests, retinoid profiling could provide an indicator for assessing mefloquine-associated adverse effects.

Breastfeeding, retinoids, and postpartum depression: a new theory.

Science.gov (United States)

Mawson, Anthony R; Xueyuan, Wang

2013-09-25

Postpartum depression (PPD) is an international public health problem affecting at least 1 in 8 mothers. Known risk factors include: giving birth to a preterm or low birth weight infant, babies with greater symptoms of illness at age 4-6 weeks, formula feeding, younger maternal age, smoking, and fatigue. Prolonged breastfeeding is associated with a reduced risk of PPD but the mechanisms are not well understood. Interventions for PPD focusing on psychosocial risk factors have been largely unsuccessful, suggesting that the condition has a mainly biological basis. The hypothesis proposed for consideration is that breastfeeding protects against PPD by maintaining endogenous retinoids (vitamin A-related compounds) below a threshold concentration. In fact, breast milk is rich in retinoids; pregnant women accumulate retinoids in liver and breast in preparation for lactation; there is increasing evidence that retinoids in higher concentration are associated with cognitive disturbances and mood disorders, including depression and suicide; and prolonged lactation reduces maternal stores of retinoids. Consistent with this hypothesis, it is estimated that an amount of vitamin A is transferred from mother to infant during the first six months of exclusive breastfeeding equivalent to 76% of a dose known to cause acute vitamin A poisoning in an adult. Breastfeeding may thus have evolutionary-adaptive functions for both mother and infant, transferring vital nutrients to an infant unable to feed itself, yet at the same time providing a natural means of reducing potentially toxic concentrations of retinoids in the mother. © 2013 Elsevier B.V. All rights reserved.

Manganese(I-Based CORMs with 5-Substituted 3-(2-PyridylPyrazole Ligands

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Ralf Mede

2017-01-01

Full Text Available The reaction of [(OC5MnBr] with substituted 3-(2-pyridylpyrazoles 2-PyPzRH (1a-l in methanol or diethyl ether yields the yellow to orange manganese(I complexes [(OC3Mn(Br(2-PyPzRH] (2a-l, the substituents R being phenyl (a, 1-naphthyl (b, 2-anthracenyl (c, 1-pyrenyl (d, 4-bromophenyl (e, 3-bromophenyl (f, duryl (g, 2-pyridyl (h, 2-furanyl (i, 2-thienyl (j, ferrocenyl (k, and 1-adamantyl (l. The carbonyl ligands are arranged facially, leading to three chemically different CO ligands due to different trans-positioned Lewis donors. The diversity of the substituent R demonstrates that this photoCORM backbone can easily be varied with a negligible influence on the central (OC3MnBr fragment, because the structural parameters and the spectroscopic data of this unit are very similar for all these derivatives. Even the ferrocenyl complex 2k shows a redox potential for the ferrocenyl subunit which is identical to the value of the free 5-ferrocenyl-3-(2-pyridylpyrazole (1k. The ease of variation of the starting 5-substituted 3-(2-pyridylpyrazoles offers a modular system to attach diverse substituents at the periphery of the photoCORM complex.

Synthesis and biological evaluation of 2-substituted benzimidazole derivatives

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Gurusamy Mariappan

2015-09-01

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

Alcohol and retinoids

DEFF Research Database (Denmark)

Crabb, D.W.; Pinairs, J.; Hasanadka, R.

2001-01-01

, M. Fang, and David W. Crabb; (2) Alcohol, vitamin A, and beta-carotene: Adverse interactions, by M. A. Leo and Charles S. Lieber; (3) Retinoic acid, hepatic stellate cells, and Kupffer cells, by Hidekazu Tsukamoto, K. Motomura, T. Miyahara, and M. Ohata; (4) Retinoid storage and metabolism in liver...

Chromatographic analysis of endogenous retinoids in tissues and serum

NARCIS (Netherlands)

Schmidt, C.K.; Brouwer, A.; Nau, H.

2003-01-01

We present a reliable, highly sensitive, and versatile method for the simultaneous determination of endogenous polar (acidic) and apolar (retinol, retinal, and retinyl esters) retinoids in various biological matrices. Following a single liquid extraction of retinoids from tissues or plasma with

Acyclic retinoid in chemoprevention of hepatocellular carcinoma: Targeting phosphorylated retinoid X receptor-α for prevention of liver carcinogenesis

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Masahito Shimizu

2012-01-01

Full Text Available One of the key features of hepatocellular carcinoma (HCC is the high rate of intrahepatic recurrence that correlates with poor prognosis. Therefore, in order to improve the clinical outcome for patients with HCC, development of a chemopreventive agent that can decrease or delay the incidence of recurrence is a critical issue for urgent investigation. Acyclic retinoid (ACR, a synthetic retinoid, successfully improves HCC patient survival by preventing recurrence and the formation of secondary tumors. A malfunction of the retinoid X receptor-α (RXRα due to phosphorylation by the Ras-MAPK signaling pathway plays a critical role in liver carcinogenesis, and ACR exerts chemopreventive effects on HCC development by inhibiting RXRα phosphorylation. Here, we review the relationship between retinoid signaling abnormalities and liver disease, the mechanisms of how RXRα phosphorylation contributes to liver carcinogenesis, and the detailed effects of ACR on preventing HCC development, especially based on the results of our basic and clinical research. We also outline the concept of "clonal deletion and inhibition" therapy, which is defined as the removal and inhibition of latent malignant clones from the liver before they expand into clinically detectable HCC, because ACR prevents the development of HCC by implementing this concept. Looking toward the future, we discuss "combination chemoprevention" using ACR as a key drug since it can generate a synergistic effect, and may thus be an effective new strategy for the prevention of HCC.

Synthesis, characterization and pharmacological evaluation of substituted phenoxy acetamide derivatives

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Rani Priyanka

2015-01-01

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

Effects of retinoids on ultraviolet-induced carcinogenesis

International Nuclear Information System (INIS)

Epstein, J.H.

1981-01-01

The evidence for effects of the retinoids on UV-induced carcinogenesis is sparse. Clinical observations indicate that topical RA can cause significant regression of premalignant actinic keratoses. Also there is some evidence that this agent can cause dissolution of some basal cell epitheliomas. However this latter effect does not appear to be of therapeutic value. Systemic retinoids are of little value in the treatment of premalignant and malignant cutaneous lesions though 13-cis-retinoic acid might be of use in the basal cell nevus syndrome. Examination of the influence of the retinoids on photocarcinogenesis essentially has been confined to RA and animal experimentation. RA in nontoxic concentrations can both stimulate and inhibit photocarcinogenesis depending upon the circumstances of the study. The mechanisms of these responses are not clear. Influences on DNA synthesis directly and/or indirectly or on immune responses may be involved in both effects. Preliminary studies with oral 13-cis-retinoic acid have not demonstrated any effects to date on UV-induced skin cancer formation

Side effects of retinoid therapy on the quality of vision

Directory of Open Access Journals (Sweden)

Bergler-Czop Beata

2016-12-01

Full Text Available Retinoids are compounds chemically related to vitamin A, which are frequently used in dermatological practice (1. They are characterized by numerous mechanisms of action leading to normalization of keratinocyte proliferation and maturation. They have anti-seborrhoeic, immunomodulatory and anti-inflammatory effects (1, 2. A number of side effects to retinoid treatment have been recorded; one group of such side effects relates to eyes and vision. Dry eye syndrome and blepharoconjunctivitis are the most common side effects, appearing in 20-50 % of patients treated with retinoids. They often contribute to the occurrence of other side-effects such as eye discomfort and contact lens intolerance. Due to the widespread use in clinical practice, the adverse effects, including ocular side effects, should be studied. To confirm the variety of adverse effects of retinoids, several case reports of rare side-effects are presented.

Substitution Structures of Large Molecules and Medium Range Correlations in Quantum Chemistry Calculations

Science.gov (United States)

Evangelisti, Luca; Pate, Brooks

2017-06-01

A study of the minimally exciting topic of agreement between experimental and measured rotational constants of molecules was performed on a set of large molecules with 16-18 heavy atoms (carbon and oxygen). The molecules are: nootkatone (C_{15}H_{22}O), cedrol (C_{15}H_{26}O), ambroxide (C_{16}H_{28}O), sclareolide (C_{16}H_{22}O_{2}), and dihydroartemisinic acid (C_{15}H_{24}O_{2}). For this set of molecules we obtained 13C-subsitution structures for six molecules (this includes two conformers of nootkatone). A comparison of theoretical structures and experimental substitution structures was performed in the spirit of the recent work of Grimme and Steinmetz.[1] Our analysis focused the center-of-mass distance of the carbon atoms in the molecules. Four different computational methods were studied: standard DFT (B3LYP), dispersion corrected DFT (B3LYP-D3BJ), hybrid DFT with dispersion correction (B2PLYP-D3), and MP2. A significant difference in these theories is how they handle medium range correlation of electrons that produce dispersion forces. For larger molecules, these dispersion forces produce an overall contraction of the molecule around the center-of-mass. DFT poorly treats this effect and produces structures that are too expanded. MP2 calculations overestimate the correction and produce structures that are too compact. Both dispersion corrected DFT methods produce structures in excellent agreement with experiment. The analysis shows that the difference in computational methods can be described by a linear error in the center-of-mass distance. This makes it possible to correct poorer performing calculations with a single scale factor. We also reexamine the issue of the "Costain error" in substitution structures and show that it is significantly larger in these systems than in the smaller molecules used by Costain to establish the error limits. [1] Stefan Grimme and Marc Steinmetz, "Effects of London dispersion correction in density functional theory on

Effect of different substitution position on the switching behavior in single-molecule device with carbon nanotube electrodes

Science.gov (United States)

Yang, Jingjuan; Han, Xiaoxiao; Yuan, Peipei; Bian, Baoan; Wang, Yixiang

2018-01-01

We investigate the electronic transport properties of dihydroazulene (DHA) and vinylheptafulvene (VHF) molecule sandwiched between two carbon nanotubes using density functional theory and non-equilibrium Green's function. The device displays significantly switching behavior between DHA and VHF isomerizations. It is found the different substitution position of F in the molecule influences the switching ratio of device, which is analyzed by transmission spectra and molecular projected self-consistent Hamiltonian. The observed negative differential resistance effect is explained by transmission spectra and transmission eigenstates of transmission peak in the bias window. The observed reverse of current in VHF form in which two H atoms on the right side of the benzene ring of the molecule are replaced by F is explained by transmission spectra and molecule-electrode coupling with the varied bias. The results suggest that the reasonable substitution position of molecule may improve the switching ratio, displaying a potential application in future molecular circuit.

Design, Synthesis and Optoelectronic Properties of Unsymmetrical Oxadiazole Based Indene Substituted Derivatives as Deep Blue Fluoroscent Materials.

Science.gov (United States)

Belavagi, Ningaraddi S; Deshapande, Narahari; Pujar, G H; Wari, M N; Inamdar, S R; Khazi, Imtiyaz Ahmed M

2015-09-01

A series of novel unsymmetrically substituted indene-oxadiazole derivatives (3a-f) have been designed and synthesized by employing palladium catalysed Suzuki cross coupling reaction in high yields. The structural integrity of all the novel compounds was established by (1)H, (13)C NMR and LC/MS analysis. These compounds are amorphous in nature and are remarkably stable to long term storage under ambient conditions. The optoelectronic properties have been studied in detail using UV-Vis absorption and Fluorescence spectroscopy. All compounds emit intense blue to green-blue fluoroscence with high quantum yields. Time resolved measurments have shown life times in the range of 1.28 to 4.51 ns. The density functional theory (DFT) calculations were carried out for all the molecules to understand their structure-property relationships. Effect of concentration studies has been carried out in different concentrations for both absorption and emission properties and from this we have identified the optimized fluoroscence concentrations for all these compounds. The indene substituted anthracene-oxadiazole derivative (3f) showed significant red shift (λmax (emi) = 490 nm) and emits intense green-blue fluoroscence with largest stokes shift of 145 nm. This compound also exhibited highest fluoroscence life time (τ) of 4.51 ns, which is very close to the standard dye coumarin-540A (4.63 ns) and better than fluorescein-548 (4.10 ns). The results demonstrated that the novel unsymmetrical indene-substituted oxadiazole derivatives could play important role in organic optoelectronic applications, such as organic light-emitting diodes (OLEDs) or as models for investigating the fluorescent structure-property relationship of the indene-functionalized oxadiazole derivatives.

Lecithin:Retinol Acyltransferase: A Key Enzyme Involved in the Retinoid (visual) Cycle

OpenAIRE

Sears, Avery E.; Palczewski, Krzysztof

2016-01-01

Lecithin:retinol acyltransferase (LRAT) catalyzes the acyl transfer from the sn-1 position of phosphatidylcholine (PC) to all-trans-retinol, creating fatty acid retinyl esters (palmitoyl, stearoyl, and some unsaturated derivatives). In the eye, these retinyl esters are substrates for the 65 kDa retinoid isomerase (RPE65). LRAT is well characterized biochemically, and recent structural data from closely related family members of the NlpC/P60 superfamily and a chimeric protein have established ...

Organochlorine contaminant and retinoid levels in blubber of common dolphins (Delphinus delphis) off northwestern Spain

International Nuclear Information System (INIS)

Tornero, Victoria; Borrell, Assumpcio; Aguilar, Alex; Forcada, Jaume; Lockyer, Christina

2006-01-01

The effect of age, sex, nutritive condition and organochlorine concentration on blubber retinoid concentrations was examined in 74 common dolphins incidentally caught off northwestern Spain. Age and blubber lipid content were strong determinants of the retinoid concentrations in males, while these variables did not account for the variation found in females. Retinoids were positively correlated with organochlorines in males and negatively in females. However, pollution levels were moderate and likely to be below threshold levels above that a toxicological response is to be expected. Thus, a cause-effect relationship between organochlorine and retinoid concentrations could not be properly established, and the observed correlation may be the result of an independent association of the two variables with age. Further research on the influence of the best predictor variables on retinoid dynamics is required to implement the use of retinoids as biomarkers of pollutant exposure in cetaceans. - Organochlorine contaminants and retinoids in common dolphins

Retinoids, race and the pathogenesis of dengue hemorrhagic fever.

Science.gov (United States)

Mawson, Anthony R

2013-12-01

Dengue hemorrhagic fever (DHF) is the most significant mosquito-borne viral disease worldwide in terms of illness, mortality and economic cost, but the pathogenesis of DHF is not well understood and there is no specific treatment or vaccine. Based on evidence of liver involvement, it is proposed that dengue virus and retinoids interact to cause cholestatic liver damage, resulting in the spillage of stored retinoids into the circulation and in an endogenous form of hypervitaminosisis A manifested by the signs and symptoms of the disease, including: fever, severe joint and bone pain, capillary leakage, thrombocytopenia, headache, and gastrointestinal symptoms. While retinoids in low concentration are essential for numerous biological functions, they are prooxidant, cytotoxic, mutagenic and teratogenic in higher concentration, especially when unbound to protein, and an endogenous form of vitamin A intoxication is recognized in cholestasis. The model tentatively explains the observations that 1) repeat infections are more severe than initial dengue virus infections; 2) the incidence of denue has increased dramatically worldwide in recent decades; 3) DHF is less prevalent in people of African ancestry than those of other racial backgrounds; and 4) infants are protected from dengue. The retinoid toxicity hypothesis of DHF predicts the co-existence of low serum concentrations of retinol coupled with high concentrations of retinoic acid and an increased percentage of retinyl esters to total vitamin A. Subject to such tests, it may be possible to treat DHF effectively using drugs that target the metabolism and expression of retinoids. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

N-6 substituted deoxygenated derivatives of L-like 5'-noraristeromycin

African Journals Online (AJOL)

Several N-6 substituted derivatives (4-11) of (+)-4'-deoxy-5'-noraristeromycin (2) and its unsaturated counterpart (3) have been prepared. The derivatives are designed to systematically vary the hydrophobic/hydrophilic balance of the lead compounds. These compounds were evaluated against a large number of viruses but ...

A possible contribution of retinoids to regulation of fetal B lymphopoiesis.

Science.gov (United States)

Chen, Xinrong; Welner, Robert S; Kincade, Paul W

2009-09-01

We recently found that all trans retinoic acid (ATRA) accelerated B lymphocyte formation. In the current study, we address the question whether retinoids account for the rapid lymphopoiesis that is characteristic of fetal progenitors. Surprisingly, addition of ATRA to fetal liver cultures actually reduced B lymphopoiesis. A pan-retinoid receptor antagonist selectively suppressed lymphocyte formation from fetal and adult progenitors, suggesting some normal contribution of retinoids to this process. Consistent with this role, B lymphopoiesis was compromised in the marrow of mice with prolonged vitamin A deficiency. Recently identified B1 progenitors from adult marrow were similar to adult B2 progenitors in that their differentiation was stimulated by ATRA. The inhibitory response observed with fetal cells was seen when adult progenitors were exposed to high doses in culture or when adult mice were treated with ATRA for 2 wk. In addition to explosive lymphocyte generation, fetal progenitors tend to be less IL-7 dependent than their adult counterparts, but ATRA did not make fetal progenitors IL-7 independent. We conclude that all known categories of B lineage progenitors are responsive to retinoids and probably regulated by these compounds under physiological conditions. Retinoids may account in part for rapid differentiation in fetal life, but not all unique features of fetal progenitors.

Temperature and Recognition Dual Responsive Poly(N-Isopropylacrylamide) and Poly(N,N-Dimethylacrylamide) with Adamantyl Side Group.

Science.gov (United States)

Dong, Qiujing; Luo, Chunhua; Li, Na; Chi, Jiaxiang; Zhang, Qingqing

2018-03-22

A series of copolymers with an adamantyl side group (poly(NIPAM-co-AdMA) and poly(DMAM-co-AdMA)) were prepared by radical copolymerization of N -isopropylacrylamide (NIPAM) and N , N -dimethylacrylamide (DMAM) with a 2-methyl-2-adamantylmethacrylate (AdMA) monomer. The structure and composition of the as-synthesized copolymers were characterized by Fourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (¹H NMR) spectroscopy, gel permeation chromatography (GPC), thermogravimetric analysis (TGA), and elemental analysis. Temperature and recognition dual responsivity of the copolymers was investigated by cloud point (T cp ) and dynamic light scattering (DLS), respectively. The results show that the as-synthesized copolymers are a kind of temperature-responsive polymer with a lower critical solution temperature (LCST). T cp was approximately consistent with the critical temperature of intermolecular copolymer association (T ass ) from DLS. For these copolymers, T cp decreases with increasing content of AdMA unit in the copolymers. After the addition of β-cyclodextrins (β-CD), T cp increases, and the increment of T cp values gradually became large with increasing content of AdMA in the copolymers. It is host-guest molecular recognition of β-CD and adamantyl groups that endows the as-synthesized copolymers with recognition-tunable thermosensitivity.

Synthesis, characterization and properties of lanthanide trifluoroacetate complexes with N-(1-adamantyl) acetamide

International Nuclear Information System (INIS)

Miranda Junior, P.; Isolani, P.C.; Vicentini, G.; Zinner, L.B.

1999-01-01

Complexes of lanthanide trifluoacetates and N-(1-adamantyl) acetamide (ADA) with composition Ln (TFA) 3 .ADA (Ln=Nd, Sm, Eu, Gd, Tb, Dy; TFA trifluoroacetate) were synthesized by titration of lanthanides with EDTA and CHN microanalytical procedures. According to IR spectra the bonding of ADA occurs through the carbonyl oxygen. Compounds of Nd 3+ , Sm 3+ and Eu 3+ present two bands attributed to v aa COO and that of Gd 3+ Tb 3+ only one. In all cases only one band is attributed to v a -s COO. The absorption spectra of the neodymium and the emission spectra of the europium compounds were determined and interpreted. (author)

Retinoids in the treatment of glioma: a new perspective

Directory of Open Access Journals (Sweden)

Mawson AR

2012-08-01

Full Text Available Anthony R MawsonDepartment of Health Policy and Management, School of Health Sciences, College of Public Service, Jackson State University, Jackson, MS, USAAbstract: Primary brain tumors are among the top ten causes of cancer-related deaths in the US. Malignant gliomas account for approximately 70% of the 22,500 new cases of malignant primary brain tumors diagnosed in adults each year and are associated with high morbidity and mortality. Despite optimal treatment, the prognosis for patients with gliomas remains poor. The use of retinoids (vitamin A and its congeners in the treatment of certain tumors was originally based on the assumption that these conditions were associated with an underlying deficiency of vitamin A and that supplementation with pharmacological doses would correct the deficiency. Yet the results of retinoid treatment have been only modestly beneficial and usually short-lived. Studies also indicate that vitamin A excess and supplementation have pro-oxidant effects and are associated with increased risks of mortality from cancer and other diseases. The therapeutic role of vitamin A in cancer thus remains uncertain and a new perspective on the facts is needed. The modest and temporary benefits of retinoid treatment could result from a process of feedback inhibition, whereby exogenous retinoid temporarily inhibits the endogenous synthesis of these compounds. In fact, repeated and/or excessive exposure of the tissues to endogenous retinoic acid may contribute to carcinogenesis. Gliomas, in particular, may result from an imbalance in retinoid receptor expression initiated by environmental factors that increase the endogenous production of retinoic acid in glia. At the receptor level, it is proposed that this imbalance is characterized by excessive expression of retinoic acid receptor-α(RARα and reduced expression of retinoic acid receptor-β (RARβ. This suggests a potential new treatment strategy for gliomas, possibly even at a

Evolution of Retinoid and Steroid Signaling: Vertebrate Diversification from an Amphioxus Perspective

Science.gov (United States)

Albalat, Ricard; Brunet, Frédéric; Laudet, Vincent; Schubert, Michael

2011-01-01

Although the physiological relevance of retinoids and steroids in vertebrates is very well established, the origin and evolution of the genetic machineries implicated in their metabolic pathways is still very poorly understood. We investigated the evolution of these genetic networks by conducting an exhaustive survey of components of the retinoid and steroid pathways in the genome of the invertebrate chordate amphioxus (Branchiostoma floridae). Due to its phylogenetic position at the base of chordates, amphioxus is a very useful model to identify and study chordate versus vertebrate innovations, both on a morphological and a genomic level. We have characterized more than 220 amphioxus genes evolutionarily related to vertebrate components of the retinoid and steroid pathways and found that, globally, amphioxus has orthologs of most of the vertebrate components of these two pathways, with some very important exceptions. For example, we failed to identify a vertebrate-like machinery for retinoid storage, transport, and delivery in amphioxus and were also unable to characterize components of the adrenal steroid pathway in this invertebrate chordate. The absence of these genes from the amphioxus genome suggests that both an elaboration and a refinement of the retinoid and steroid pathways took place at the base of the vertebrate lineage. In stark contrast, we also identified massive amplifications in some amphioxus gene families, most extensively in the short-chain dehydrogenase/reductase superfamily, which, based on phylogenetic and genomic linkage analyses, were likely the result of duplications specific to the amphioxus lineage. In sum, this detailed characterization of genes implicated in retinoid and steroid signaling in amphioxus allows us not only to reconstruct an outline of these pathways in the ancestral chordate but also to discuss functional innovations in retinoid homeostasis and steroid-dependent regulation in both cephalochordate and vertebrate evolution

Computational Study on Substituted s-Triazine Derivatives as Energetic Materials

Directory of Open Access Journals (Sweden)

Vikas D. Ghule

2012-01-01

Full Text Available s-Triazine is the essential candidate of many energetic compounds due to its high nitrogen content, enthalpy of formation and thermal stability. The present study explores s-triazine derivatives in which different -NO2, -NH2 and -N3 substituted azoles are attached to the triazine ring via C-N linkage. The density functional theory is used to predict geometries, heats of formation and other energetic properties. Among the designed compounds, -N3 derivatives show very high heats of formation. The densities for designed compounds were predicted by using the crystal packing calculations. Introduction of -NO2 group improves density as compared to -NH2 and -N3, their order of increasing density can be given as NO2>N3>NH2. Analysis of the bond dissociation energies for C-NO2, C-NH2 and C-N3 bonds indicates that substitutions of the -N3 and -NH2 group are favorable for enhancing the thermal stability of s-triazine derivatives. The nitro and azido derivatives of triazine are found to be promising candidates for the synthetic studies.

Asymmetric syntheses of 3,4-disubstituted tetrahydroquinoline derivatives using (+)- sparteine-mediated electrophilic substitution

International Nuclear Information System (INIS)

Choi, Yun Soo; Kang, Kyoung Hee; Park, Yong Sun

2015-01-01

Tetrahydroquinolines bearing substituents are frequently found as a substructure in a number of alkaloids and natural products. Since their individual stereoisomers displays different biological activities, it is desirable to develop a highly stereoselective synthetic method for tetrahydroquinolines. While some progress has recently been made toward the development of asymmetric synthetic methods for tetrahydroquinolines, it is still a challenging topic in organic synthesis. In order to investigate the source of diastereoselection attained in the substitution reaction with a racemic epoxide, we examined the substitution of 2 with an excess amount of racemic p-chlorophenyl-substituted oxirane. We have developed a novel method for the asymmetric synthesis of trans-3,4-diaryl-substituted tetrahy- droquinolines from ortho-substituted N-pivaloyl anilines. The enantioselective process includes (+)-sparteine-mediated stereoselective lithiati on, kinetic resolution of epoxides in substitution, and stereospecific Mitsu nobu cyclization as the key reactions. The simple protocol can provide highly functionalized tetrahydroqu inoline rings and would allow their further functionalization to access more complex target molecules

Asymmetric syntheses of 3,4-disubstituted tetrahydroquinoline derivatives using (+)- sparteine-mediated electrophilic substitution

Energy Technology Data Exchange (ETDEWEB)

Choi, Yun Soo; Kang, Kyoung Hee; Park, Yong Sun [Dept. of Chemistry, Konkuk University, Seoul (Korea, Republic of)

2015-05-15

Tetrahydroquinolines bearing substituents are frequently found as a substructure in a number of alkaloids and natural products. Since their individual stereoisomers displays different biological activities, it is desirable to develop a highly stereoselective synthetic method for tetrahydroquinolines. While some progress has recently been made toward the development of asymmetric synthetic methods for tetrahydroquinolines, it is still a challenging topic in organic synthesis. In order to investigate the source of diastereoselection attained in the substitution reaction with a racemic epoxide, we examined the substitution of 2 with an excess amount of racemic p-chlorophenyl-substituted oxirane. We have developed a novel method for the asymmetric synthesis of trans-3,4-diaryl-substituted tetrahy- droquinolines from ortho-substituted N-pivaloyl anilines. The enantioselective process includes (+)-sparteine-mediated stereoselective lithiati on, kinetic resolution of epoxides in substitution, and stereospecific Mitsu nobu cyclization as the key reactions. The simple protocol can provide highly functionalized tetrahydroqu inoline rings and would allow their further functionalization to access more complex target molecules.

Therapy of psoriasis with retinoid plus PUVA

International Nuclear Information System (INIS)

Heidbreder, G.; Christophers, E.

1979-01-01

In a group of 40 patients suffering from wide-spread psoriasis oral administration of a retinoid (Ro 10-9359) was followed by PUVA therapy. The clearance rate was increased by 30% as compared to PUVA alone. Except for cheilitis no side effects were seen. Histological analysis in 20 patients before, during and after therapy revealed an intensification of psoriatic tissue changes after retinoid treatment. Loss of corneal layers, massive exoserosis, and neutrophil migration were prominent features. Mitotic counts were not increased by the pretreatment. The increased susceptibility of diseased skin to PUVA as produced by this drug appears to be based on several factors related to the tissue changes revealed by histology. (orig.) [de

Uptake and processing of [3H]retinoids in rat liver studied by electron microscopic autoradiography

International Nuclear Information System (INIS)

Hendriks, H.F.; Elhanany, E.; Brouwer, A.; de Leeuw, A.M.; Knook, D.L.

1988-01-01

The role of rat liver cell organelles in retinoid uptake and processing was studied by electron microscopic autoradiography. [ 3 H]Retinoids were administered either orally, to make an inventory of the cell organelles involved, or intravenously as chylomicron remnant constituents to study retinoid processing by the liver with time. No qualitative differences were observed between the two routes of administration. Time-related changes in the distribution of grains were studied using chylomicron remnant [ 3 H]retinoids. The percentages of grains observed over cells and the space of Disse at 5 and 30 min after administration were, respectively: parenchymal cells, 72.6 and 70.4%; fat-storing cells, 5.0 and 18.1%, and the space of Disse, 14.4 and 8.9%. Low numbers of grains were observed over endothelial and Kupffer cells. The percentages of grains observed over parenchymal cell organelles were, respectively: sinusoidal area, 59.6 and 34.4%; smooth endoplasmic reticulum associated with glycogen, 13.8 and 13.4%; mitochondria, 5.4 and 13.6%; rough endoplasmic reticulum, 4.2 and 7.3%, and rough endoplasmic reticulum associated with mitochondria, 3.7 and 6.5%. It is concluded that chylomicron remnant [ 3 H]retinoids in combination with electron microscopic autoradiography provide a good system to study the liver processing of retinoids in vivo. These results, obtained in the intact liver under physiological conditions, further substantiate that retinoids are processed through parenchymal cells before storage occurs in fat-storing cell lipid droplets, that retinoid uptake is not mediated through lysosomes and that the endoplasmic reticulum is a major organelle in retinoid processing

Optical properties of new 5-(4-phenylethynyl)-substituted-1,10-phenanthroline derivatives

International Nuclear Information System (INIS)

Guerin, Juliette; Aronica, Christophe; Boeuf, Gaelle; Chauvin, Jerome; Moreau, Juliette; Lemercier, Gilles

2011-01-01

The synthesis and optical properties of a novel family of 5-substituted-1,10-phenanthroline derivatives are reported herein. One carbon-carbon triple-bond function was introduced using a Sonogashira cross-coupling reaction. The effects on optical properties, of the substitution with electro-withdrawing or -donating substituents in the 5th position of the 1,10-phenanthroline are investigated. Experimental chemical structure-polarisability relationship is analyzed according to the Lippert-Mataga correlation and compared to a theoretical study carried out with DFT calculations. These compounds are promising candidates for a fine-tuning of the internal charge-transfers but also as potential nonlinear chromophores and ligands within multifunctional coordination complexes. - Highlights: → Synthesis and optical properties of new 5-substituted-1,10-phenanthroline derivatives. → Sonogashira reaction was used for the substitution. → Structure-polarisability relationship analyzed according to Lippert-Mataga correlation. → Theoretical study was carried out with DFT calculations. → Fine-tuning of the internal charge-transfers within nonlinear compounds.

DISSOCIATIVE PHOTOIONIZATION OF POLYCYCLIC AROMATIC HYDROCARBON MOLECULES CARRYING AN ETHYNYL GROUP

Energy Technology Data Exchange (ETDEWEB)

Rouillé, G.; Krasnokutski, S. A.; Fulvio, D.; Jäger, C. [Laboratory Astrophysics Group of the Max Planck Institute for Astronomy at the Friedrich Schiller University Jena, Institute of Solid State Physics, Helmholtzweg 3, D-07743 Jena (Germany); Henning, Th. [Max Planck Institute for Astronomy, Königstuhl 17, D-69117 Heidelberg (Germany); Garcia, G. A.; Tang, X.-F.; Nahon, L., E-mail: cornelia.jaeger@uni-jena.de [Synchrotron SOLEIL, L’Orme des Merisiers, Saint-Aubin BP 48, F-91192 Gif-sur-Yvette Cedex (France)

2015-09-10

The life cycle of the population of interstellar polycyclic aromatic hydrocarbon (PAH) molecules depends partly on the photostability of the individual species. We have studied the dissociative photoionization of two ethynyl-substituted PAH species, namely, 9-ethynylphenanthrene and 1-ethynylpyrene. Their adiabatic ionization energy and the appearance energy of fragment ions have been measured with the photoelectron photoion coincidence spectroscopy technique. The adiabatic ionization energy has been found at 7.84 ± 0.02 eV for 9-ethynylphenanthrene and at 7.41 ± 0.02 eV for 1-ethynylpyrene. These values are similar to those determined for the corresponding non-substituted PAH molecules phenanthrene and pyrene. The appearance energy of the fragment ion indicative of the loss of a H atom following photoionization is also similar for either ethynyl-substituted PAH molecule and its non-substituted counterpart. The measurements are used to estimate the critical energy for the loss of a H atom by the PAH cations and the stability of ethynyl-substituted PAH molecules upon photoionization. We conclude that these PAH derivatives are as photostable as the non-substituted species in H i regions. If present in the interstellar medium, they may play an important role in the growth of interstellar PAH molecules.

Liposomal Formulation of Retinoids Designed for Enzyme Triggered Release

DEFF Research Database (Denmark)

Pedersen, Palle Jacob; Adolph, Sidsel Kramshøj; Subramanian, Arun Kumar

2010-01-01

The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesi...... displayed IC50 values in the range of 3-19 mu M toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A(2), while no significant cell death was observed in the absence of the enzyme....

Versatility of 7-Substituted Coumarin Molecules as Antimycobacterial Agents, Neuronal Enzyme Inhibitors and Neuroprotective Agents

Directory of Open Access Journals (Sweden)

Erika Kapp

2017-09-01

Full Text Available A medium-throughput screen using Mycobacterium tuberculosis H37Rv was employed to screen an in-house library of structurally diverse compounds for antimycobacterial activity. In this initial screen, eleven 7-substituted coumarin derivatives with confirmed monoamine oxidase-B and cholinesterase inhibitory activities, demonstrated growth inhibition of more than 50% at 50 µM. This prompted further exploration of all the 7-substituted coumarins in our library. Four compounds showed promising MIC99 values of 8.31–29.70 µM and 44.15–57.17 µM on M. tuberculosis H37Rv in independent assays using GAST-Fe and 7H9+OADC media, respectively. These compounds were found to bind to albumin, which may explain the variations in MIC between the two assays. Preliminary data showed that they were able to maintain their activity in fluoroquinolone resistant mycobacteria. Structure-activity relationships indicated that structural modification on position 4 and/or 7 of the coumarin scaffold could direct the selectivity towards either the inhibition of neuronal enzymes or the antimycobacterial effect. Moderate cytotoxicities were observed for these compounds and slight selectivity towards mycobacteria was indicated. Further neuroprotective assays showed significant neuroprotection for selected compounds irrespective of their neuronal enzyme inhibitory properties. These coumarin molecules are thus interesting lead compounds that may provide insight into the design of new antimicrobacterial and neuroprotective agents.

Cumulative irritation potential of topical retinoid formulations.

Science.gov (United States)

Leyden, James J; Grossman, Rachel; Nighland, Marge

2008-08-01

Localized irritation can limit treatment success with topical retinoids such as tretinoin and adapalene. The factors that influence irritant reactions have been shown to include individual skin sensitivity, the particular retinoid and concentration used, and the vehicle formulation. To compare the cutaneous tolerability of tretinoin 0.04% microsphere gel (TMG) with that of adapalene 0.3% gel and a standard tretinoin 0.025% cream. The results of 2 randomized, investigator-blinded studies of 2 to 3 weeks' duration, which utilized a split-face method to compare cumulative irritation scores induced by topical retinoids in subjects with healthy skin, were combined. Study 1 compared TMG 0.04% with adapalene 0.3% gel over 2 weeks, while study 2 compared TMG 0.04% with tretinoin 0.025% cream over 3 weeks. In study 1, TMG 0.04% was associated with significantly lower cumulative scores for erythema, dryness, and burning/stinging than adapalene 0.3% gel. However, in study 2, there were no significant differences in cumulative irritation scores between TMG 0.04% and tretinoin 0.025% cream. Measurements of erythema by a chromameter showed no significant differences between the test formulations in either study. Cutaneous tolerance of TMG 0.04% on the face was superior to that of adapalene 0.3% gel and similar to that of a standard tretinoin cream containing a lower concentration of the drug (0.025%).

Retinoids in the treatment of glioma: a new perspective.

Science.gov (United States)

Mawson, Anthony R

2012-01-01

Primary brain tumors are among the top ten causes of cancer-related deaths in the US. Malignant gliomas account for approximately 70% of the 22,500 new cases of malignant primary brain tumors diagnosed in adults each year and are associated with high morbidity and mortality. Despite optimal treatment, the prognosis for patients with gliomas remains poor. The use of retinoids (vitamin A and its congeners) in the treatment of certain tumors was originally based on the assumption that these conditions were associated with an underlying deficiency of vitamin A and that supplementation with pharmacological doses would correct the deficiency. Yet the results of retinoid treatment have been only modestly beneficial and usually short-lived. Studies also indicate that vitamin A excess and supplementation have pro-oxidant effects and are associated with increased risks of mortality from cancer and other diseases. The therapeutic role of vitamin A in cancer thus remains uncertain and a new perspective on the facts is needed. The modest and temporary benefits of retinoid treatment could result from a process of feedback inhibition, whereby exogenous retinoid temporarily inhibits the endogenous synthesis of these compounds. In fact, repeated and/or excessive exposure of the tissues to endogenous retinoic acid may contribute to carcinogenesis. Gliomas, in particular, may result from an imbalance in retinoid receptor expression initiated by environmental factors that increase the endogenous production of retinoic acid in glia. At the receptor level, it is proposed that this imbalance is characterized by excessive expression of retinoic acid receptor-α (RARα) and reduced expression of retinoic acid receptor-β (RARβ). This suggests a potential new treatment strategy for gliomas, possibly even at a late stage of the disease, ie, to combine the use of a RARα antagonist and a RARβ agonist. According to this hypothesis, the RARα antagonist would be expected to inhibit RAR�

Retinoids in the treatment of glioma: a new perspective

International Nuclear Information System (INIS)

Mawson, Anthony R

2012-01-01

Primary brain tumors are among the top ten causes of cancer-related deaths in the US. Malignant gliomas account for approximately 70% of the 22,500 new cases of malignant primary brain tumors diagnosed in adults each year and are associated with high morbidity and mortality. Despite optimal treatment, the prognosis for patients with gliomas remains poor. The use of retinoids (vitamin A and its congeners) in the treatment of certain tumors was originally based on the assumption that these conditions were associated with an underlying deficiency of vitamin A and that supplementation with pharmacological doses would correct the deficiency. Yet the results of retinoid treatment have been only modestly beneficial and usually short-lived. Studies also indicate that vitamin A excess and supplementation have pro-oxidant effects and are associated with increased risks of mortality from cancer and other diseases. The therapeutic role of vitamin A in cancer thus remains uncertain and a new perspective on the facts is needed. The modest and temporary benefits of retinoid treatment could result from a process of feedback inhibition, whereby exogenous retinoid temporarily inhibits the endogenous synthesis of these compounds. In fact, repeated and/or excessive exposure of the tissues to endogenous retinoic acid may contribute to carcinogenesis. Gliomas, in particular, may result from an imbalance in retinoid receptor expression initiated by environmental factors that increase the endogenous production of retinoic acid in glia. At the receptor level, it is proposed that this imbalance is characterized by excessive expression of retinoic acid receptor-α (RARα) and reduced expression of retinoic acid receptor-β (RARβ). This suggests a potential new treatment strategy for gliomas, possibly even at a late stage of the disease, ie, to combine the use of a RARα antagonist and a RARβ agonist. According to this hypothesis, the RARα antagonist would be expected to inhibit RAR�

Modeling of flux, binding and substitution of urea molecules in the urea transporter dvUT.

Science.gov (United States)

Zhang, Hai-Tian; Wang, Zhe; Yu, Tao; Sang, Jian-Ping; Zou, Xian-Wu; Zou, Xiaoqin

2017-09-01

Urea transporters (UTs) are transmembrane proteins that transport urea molecules across cell membranes and play a crucial role in urea excretion and water balance. Modeling the functional characteristics of UTs helps us understand how their structures accomplish the functions at the atomic level, and facilitates future therapeutic design targeting the UTs. This study was based on the crystal structure of Desulfovibrio vulgaris urea transporter (dvUT). To model the binding behavior of urea molecules in dvUT, we constructed a cooperative binding model. To model the substitution of urea by the urea analogue N,N'-dimethylurea (DMU) in dvUT, we calculated the occupation probability of DMU along the urea pore and the ratio of the occupation probabilities of DMU at the external (S ext ) and internal (S int ) binding sites, and we established the mutual substitution rule for binding and substitution of urea and DMU. Based on these calculations and modelings, together with the use of the Monte Carlo (MC) method, we further modeled the urea flux in dvUT, equilibrium urea binding to dvUT, and the substitution of urea by DMU in the dvUT. Our modeling results are in good agreement with the existing experimental functional data. Furthermore, the modelings have discovered the microscopic process and mechanisms of those functional characteristics. The methods and the results would help our future understanding of the underlying mechanisms of the diseases associated with impaired UT functions and rational drug design for the treatment of these diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Muonium substituted molecules

International Nuclear Information System (INIS)

Cox, S.F.J.

1990-12-01

The manner in which Muon Spin Rotation and Level Crossing Resonance are used to characterise muonium substituted organic radicals is described, and illustrated with spectra for the ethyl radical and related species. Comparison with electron spin resonance data for the unsubstituted radicals reveals significant structural and hyperfine isotope effects which can be traced to the effects of zero point motion. The first comparable results for a diamagnetic species, exhibiting a quadrupole isotope effect by comparison with conventional nuclear quadrupole resonance data, are presented and discussed. (author)

Effect of five-membered ring and heteroatom substitution on charge transport properties of perylene discotic derivatives: A theoretical approach

Energy Technology Data Exchange (ETDEWEB)

Navarro, Amparo, E-mail: anavarro@ujaen.es; Fernández-Liencres, M. Paz; Peña-Ruiz, Tomás; Granadino-Roldán, José M.; Fernández-Gómez, Manuel [Departamento de Química Física y Analítica, Universidad de Jaén, Campus Las Lagunillas, E23071 Jaén (Spain); García, Gregorio [Instituto de Energía Solar and Departamento TFB, E.T.S.I. Telecomunicación, Universidad Politécnica de Madrid, Ciudad Universitaria, Madrid 28040 (Spain)

2016-08-07

Density functional theory calculations were carried out to investigate the evolvement of charge transport properties of a set of new discotic systems as a function of ring and heteroatom (B, Si, S, and Se) substitution on the basic structure of perylene. The replacement of six-membered rings by five-membered rings in the reference compound has shown a prominent effect on the electron reorganization energy that decreases ∼0.2 eV from perylene to the new carbon five-membered ring derivative. Heteroatom substitution with boron also revealed to lower the LUMO energy level and increase the electron affinity, therefore lowering the electron injection barrier compared to perylene. Since the rate of the charge transfer between two molecules in columnar discotic systems is strongly dependent on the orientation of the stacked cores, the total energy and transfer integral of a dimer as a disc is rotated with respect to the other along the stacking axis have been predicted. Aimed at obtaining a more realistic approach to the bulk structure, the molecular geometry of clusters made up of five discs was fully optimized, and charge transfer rate and mobilities were estimated for charge transport along a one dimensional pathway. Heteroatom substitution with selenium yields electron transfer integral values ∼0.3 eV with a relative disc orientation of 25°, which is the preferred angle according to the dimer energy profile. All the results indicate that the tetraselenium-substituted derivative, not synthetized so far, could be a promising candidate among those studied in this work for the fabrication of n-type semiconductors based on columnar discotic liquid crystals materials.

N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor-specific ABC transporter ABCA4 (ABCR).

Science.gov (United States)

Beharry, Seelochan; Zhong, Ming; Molday, Robert S

2004-12-24

ABCA4, a member of the family of ATP binding cassette (ABC) proteins found in rod and cone photoreceptors, has been implicated in the transport of retinoid compounds across the outer segment disk membrane following the photoactivation of rhodopsin. Mutations in the ABCA4 gene are responsible for Stargardt macular dystrophy and related retinal degenerative diseases that cause a loss in vision. To identify the retinoid substrate that interacts with ABCA4, we have isolated ABCA4 from rod outer segment disk membranes on an immunoaffinity matrix and analyzed retinoid compounds that bind to ABCA4 using high performance liquid chromatography and radiolabeling methods. When all-trans-retinal was added to ABCA4 in the presence of phosphatidylethanolamine, approximately 0.9 mol of N-retinylidene-phosphatidylethanolamine and 0.3 mol of all-trans-retinal were bound per mol of ABCA4 with an apparent K(d) of 2-5 microm. ATP and GTP released these retinoids from ABCA4, whereas ADP, GDP, and nonhydrolyzable derivatives, adenosine 5'-(beta,gamma-imido)triphosphate and guanosine 5'-(beta,gamma-imido)triphosphate, were ineffective. One mole of N-retinyl-phosphatidylethanolamine, the reduced form of N-retinylidene-phosphatidylethanolamine, bound per mol of ABCA4, whereas 0.3 mol of all-trans-retinal were bound in the absence of phosphatidylethanolamine. No binding of all-trans-retinol to ABCA4 was observed. Our results indicate that ABCA4 preferentially binds N-retinylidene-phosphatidylethanolamine with high affinity in the absence of ATP. Our studies further suggest that ATP binding and hydrolysis induces a protein conformational change that causes N-retinylidene-phosphatidylethanolamine to dissociate from ABCA4.

Retinoid inhibition of in vitro invasion of human amnion basement membrane by human tumor cells

International Nuclear Information System (INIS)

Fazely, F.; Ledinko, N.; Smith, D.J.

1986-01-01

The biological activity of retinoids was assayed in an in vitro quantitative assay of human tumor cell invasion using human amnion basement membrane (BM). The effects measured were the inhibition of tumor cell migration through the BM and tumor cell degradative enzyme activity on 14 C-proline labeled collagenous and noncollagenous components of the BM. The human lung carcinoma A549 or the human Ewing's sarcoma TC-106 cell lines treated with retinoids for two days were incubated on the BM in the absence of retinoids. A dose-dependent inhibition of cell invasion was produced by retinoids. Among the retinoids tested, the most powerful was retinol acetate which inhibited invasion by 50% of A549 cells at a concentration of 0.009 μg/mL, and of TC-106 cells at 0.07 μg/mL. Retinol acetate inhibited A549 and TC-106 cell growth by approximately 50% at levels over 100-fold higher than those needed for antiinvasive activity. Retinol acetate was about 20 times more potent than retinoic acid and 30 times more potent than retinol palmitate. The model system will be useful for investigating antiinvasive activity of other retinoids as well as other compounds

Identification of Novel Retinoid Targets in Prostate Cancer

National Research Council Canada - National Science Library

Piedrafita, F. J

2006-01-01

.... However except for the efficient treatment of acute promyelocytic leukemia and certain skin disorders most natural and synthetic retinoids have failed in clinical trials because of toxicity and limited activity...

Synthesis, characterization of bay-substituted perylene diimide based D-A-D type small molecules and their applications as a non-fullerene electron acceptor in polymer solar cells

Directory of Open Access Journals (Sweden)

Ramasamy Ganesamoorthy

2018-03-01

Full Text Available We report a series of bay substituted perylene diimide based donor-acceptor-donor (D-A-D type small molecule acceptor derivatives such as S-I, S-II, S-III and S-IV for small molecule based organic solar cell (SM-OSC applications. The electron rich thiophene derivatives such as thiophene, 2-hexylthiophene, 2,2′-bithiophene, and 5-hexyl-2,2′-bithiophene were used as a donor (D, and perylene diimide was used as an acceptor (A. The synthesized small molecules were confirmed by FT-IR, NMR, and HR-MS. The small molecules showed wide and strong absorption in the UV-vis region up to 750 nm, which reduced the optical band gap to <2 eV. The calculated highest occupied molecular orbital (HOMO and the lowest unoccupied molecular orbital (LUMO were comparable with those of the PC61BM. Scanning electron microscope (SEM studies confirmed the aggregation of the small molecules, S-I to S-IV. Small molecules showed thermal stability up to 300 °C. In bulk heterojunction organic solar cells (BHJ-OSCs, the S-I based device showed a maximum power conversion efficiency (PCE of 0.12% with P3HT polymer donor. The PCE was declined with respect to the number of thiophene units and the flexible alkyl chain in the bay position. Keywords: Perylene diimide, Donor–acceptor, Small molecule, Non-fullerene, Suzuki coupling

Bovine cumulus-granulosa cells contain biologically active retinoid receptors that can respond to retinoic acid

Directory of Open Access Journals (Sweden)

Malayer Jerry

2003-11-01

Full Text Available Abstract Retinoids, a class of compounds that include retinol and its metabolite, retinoic acid, are absolutely essential for ovarian steroid production, oocyte maturation, and early embryogenesis. Previous studies have detected high concentrations of retinol in bovine large follicles. Further, administration of retinol in vivo and supplementation of retinoic acid during in vitro maturation results in enhanced embryonic development. In the present study, we hypothesized that retinoids administered either in vivo previously or in vitro can exert receptor-mediated effects in cumulus-granulosa cells. Total RNA extracted from in vitro cultured cumulus-granulosa cells was subjected to reverse transcription polymerase chain reaction (RT-PCR and mRNA expression for retinol binding protein (RBP, retinoic acid receptor alpha (RARalpha, retinoic acid receptor beta (RARbeta, retinoic acid receptor gamma (RARgamma, retinoid X receptor alpha (RXRalpha, retinoid X receptor beta (RXRbeta, retinaldehyde dehydrogenase-2 (RALDH-2, and peroxisome proliferator activated receptor gamma (PPARgamma. Transcripts were detected for RBP, RARalpha, RARgamma, RXRalpha, RXRbeta, RALDH-2, and PPARgamma. Expression of RARbeta was not detected in cumulus-granulosa cells. Using western blotting, immunoreactive RARalpha, and RXRbeta protein was also detected in bovine cumulus-granulosa cells. The biological activity of these endogenous retinoid receptors was tested using a transient reporter assay using the pAAV-MCS-betaRARE-Luc vector. Addition of 0.5 and 1 micro molar all-trans retinoic acid significantly (P trans retinol stimulated a mild increase in reporter activity, however, the increase was not statistically significant. Based on these results we conclude that cumulus cells contain endogenously active retinoid receptors and may also be competent to synthesize retinoic acid using the precursor, retinol. These results also indirectly provide evidence that retinoids

Amino acid derived 1,4-dialkyl substituted imidazolones

DEFF Research Database (Denmark)

Diness, Frederik; Meldal, Morten Peter

2010-01-01

A general method for synthesis of 1,4-substituted imidazolones from amino acids on solid support or in solution has been developed. Amino acid derived 3-Boc-(1,3)-oxazinane (Box) protected amino aldehyde building blocks were coupled through urea bonds to the amino terminal of dipeptides or amino...... acids. Upon acidic release, the aldehyde instantaneously formed the cyclic N-carbamyliminium ion, which rearranged to the corresponding imidazolone. Under strongly acidic conditions the imidazolones acted as nuclophiles in the Pictet-Spengler reaction....

Antiseptic Effects of New 3'-N-Substituted Carbazole Derivatives In Vitro and In Vivo.

Science.gov (United States)

Lee, Wonhwa; Kwak, Soyoung; Yun, Eunju; Lee, Jee Hyun; Na, MinKyun; Song, Gyu-Yong; Bae, Jong-Sup

2015-08-01

Inhibition of high-mobility group box 1 (HMGB1) protein and restoration of endothelial integrity are emerging as attractive therapeutic strategies in the management of sepsis. Here, new five structurally related 3'-N-substituted carbazole derivatives were examined for their effects on lipopolysaccharide (LPS)-mediated or cecal ligation and puncture (CLP)-mediated release of HMGB1 and on modulation of HMGB1-mediated inflammatory responses. We accessed this question by monitoring the effects of posttreatment carbazole derivatives on LPS- and CLP-mediated release of HMGB1 and HMGB1-mediated regulation of proinflammatory responses in human umbilical vein endothelial cells (HUVECs) and septic mice. The new 3'-N-substituted carbazole derivatives 1-5 inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. New compounds also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with each compound reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in mice. These results indicate that the new 3'-N-substituted carbazole derivatives could be candidate therapeutic agents for various severe vascular inflammatory diseases owing to their inhibition of the HMGB1 signaling pathway.

Cu-catalyzed aerobic oxidative cyclizations of 3-N-hydroxyamino-1,2-propadienes with alcohols, thiols, and amines to form α-O-, S-, and N-substituted 4-methylquinoline derivatives.

Science.gov (United States)

Sharma, Pankaj; Liu, Rai-Shung

2015-03-16

A one-pot, two-step synthesis of α-O-, S-, and N-substituted 4-methylquinoline derivatives through Cu-catalyzed aerobic oxidations of N-hydroxyaminoallenes with alcohols, thiols, and amines is described. This reaction sequence involves an initial oxidation of N-hydroxyaminoallenes with NuH (Nu = OH, OR, NHR, and SR) to form 3-substituted 2-en-1-ones, followed by Brønsted acid catalyzed intramolecular cyclizations of the resulting products. Our mechanistic analysis suggests that the reactions proceed through a radical-type mechanism rather than a typical nitrone-intermediate route. The utility of this new Cu-catalyzed reaction is shown by its applicability to the synthesis of several 2-amino-4-methylquinoline derivatives, which are known to be key precursors to several bioactive molecules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of retinoid vitamin A-vitamin B6 conjugate analogues for antiviral chemotherapy

International Nuclear Information System (INIS)

Kesel, Andreas J.

2003-01-01

The synthesis of retinoid vitamin A-vitamin B 6 conjugate analogues from a vitamin B 6 coenzyme analogue and putative HIV-1 trans-activating transcriptional regulatory protein Tat antagonist (Z)-5 ' -O-phosphono-pyridoxylidenerhodanine (B6PR) monosodium salt hemiheptadecahydrate [(Z)-B6PRNa8.5H 2 O] is discussed here. All-trans-retinoic acid (ATRA) is coupled to B6PR by a modified Stork enamine acylation. It results in a product library of more than eight compounds, each with at least one intact all-trans or 13-cis vitamin A double bond system. This yellow oily concentrate mixture was subjected to matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry (MS), UV/VIS-spectrophotometry, and proton nuclear magnetic resonance spectroscopy ( 1 H-NMR). The chemical structures of six components of the concentrate mixture could be established by combination of these analytical methods. The two main components are 65% 2 ' C,3O-(all-trans-retinylidyne)B6PT (B6RA) and 25% 2 ' C-(all-trans-retinoyl)B6PT, chemically derived from (5RS)-5-(5 ' -O-phosphono-pyridoxyl)-2,4-thiazolidinedione (B6PT). This new retinoid selection could be of further interest in antiviral applications, especially treating conditions caused by RNA viruses like HIV

Exploring (novel) gene expression during retinoid-induced maturation and cell death of acute promyelocytic leukemia.

Science.gov (United States)

Benoit, G R; Tong, J H; Balajthy, Z; Lanotte, M

2001-01-01

During recent years, reports have shown that biological responses of acute promyelocytic leukemia (APL) cells to retinoids are more complex than initially envisioned. PML-RARalpha chimeric protein disturbs various biological processes such as cell proliferation, differentiation, and apoptosis. The distinct biological programs that regulate these processes stem from specific transcriptional activation of distinct (but overlapping) sets of genes. These programs are sometimes mutually exclusive and depend on whether the signals are delivered by RAR or RXR agonists. Furthermore, evidence that retinoid nuclear signaling by retinoid, on its own, is not enough to trigger these cellular responses is rapidly accumulating. Indeed, work with NB4 cells show that the fate of APL cells treated by retinoid depends on complex signaling cross-talk. Elucidation of the sequence of events and cascades of transcriptional regulation necessary for APL cell maturation will be an additional tool with which to further improve therapy by retinoids. In this task, the classical techniques used to analyze gene expression have proved time consuming, and their yield has been limited. Global analyses of the APL cell transcriptome are needed. We review the technical approaches currently available (differential display, complementary DNA microarrays), to identify novel genes involved in the determination of cell fate.

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

Science.gov (United States)

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

2018-04-01

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

Evaluation of retinoids for induction of the redundant gene ABCD2 as an alternative treatment option in X-linked adrenoleukodystrophy.

Directory of Open Access Journals (Sweden)

Franziska D Weber

Full Text Available X-linked adrenoleukodystrophy (X-ALD, the most common peroxisomal disorder, is a clinically heterogeneous disease that can manifest as devastating inflammatory cerebral demyelination (CALD leading to death of affected males. Currently, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT. However, HSCT is only effective when performed at an early stage because the inflammation may progress for eighteen months after HSCT. Thus, alternative treatment options able to immediately halt the progression are urgently needed. X-ALD is caused by mutations in the ABCD1 gene, encoding the peroxisomal membrane protein ABCD1, resulting in impaired very long-chain fatty acid metabolism. The related ABCD2 protein is able to functionally compensate for ABCD1-deficiency both in vitro and in vivo. Recently, we demonstrated that of the cell types derived from CD34+ stem cells, predominantly monocytes but not lymphocytes are metabolically impaired in X-ALD. As ABCD2 is virtually not expressed in these cells, we hypothesize that a pharmacological up-regulation of ABCD2 should compensate metabolically and halt the inflammation in CALD. Retinoids are anti-inflammatory compounds known to act on ABCD2. Here, we investigated the capacity of selected retinoids for ABCD2 induction in human monocytes/macrophages. In THP-1 cells, 13-cis-retinoic acid reached the highest, fivefold, increase in ABCD2 expression. To test the efficacy of retinoids in vivo, we analyzed ABCD2 mRNA levels in blood cells isolated from acne patients receiving 13-cis-retinoic acid therapy. In treated acne patients, ABCD2 mRNA levels were comparable to pre-treatment levels in monocytes and lymphocytes. Nevertheless, when primary monocytes were in vitro differentiated into macrophages and treated with 13-cis-retinoic acid, we observed a fourfold induction of ABCD2. However, the level of ABCD2 induction obtained by retinoids alone is probably not of therapeutic relevance

Multicomponent One-Pot Synthesis of Substituted Hantzsch Thiazole Derivatives Under Solvent Free Conditions

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Bhaskar S. Dawane

2009-01-01

Full Text Available Thiazole derivatives were prepared by one-pot procedure by the reaction of α-haloketones, thiourea and substituted o-hydroxybenzaldehyde under environmentally solvent free conditions.

Natural derivatives of diphenolic acid as substitutes for bisphenol-A

Science.gov (United States)

Ertl, Johanna; Cerri, Elisa; Rizzuto, Matteo; Caretti, Daniele

2014-05-01

Diphenolic acid had been originally used in the first epoxy resins and was later on forgotten as it was substituted by the cheaper bisphenol A. But in the recent years major health concerns have been raised as bisphenol A has a pseudo-hormonal effect on the body, playing the role of estrogen it can cause a severe impact on the organism, especially in males. Moreover it is produced from acetone and phenol, both from fossil, and thus limited resources. On the contrary, diphenolic acid is synthesized from levulinic acid and phenol. Levulinic acid being directly produced by hydrolysis of biomass. By substituting the fossil phenol with natural phenols from lignin or plant extraction we are able to synthesize a fully renewable substitute for bisphenol A. The reactions to yield an epoxy resin have been examined and the reactivity with epichlorohydrin is satisfying. Moreover, some of the derivatives of diphenolic acid have interesting curing properties and preliminary results show excellent properties of the cured resin, including thermal stability and pencil hardness.

In silico binding affinity studies of N-9 substituted 6-(4-(4-propoxyphenylpiperazin-1-yl-9H-purine derivatives-Target for P70-S6K1 & PI3K-δ kinases

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Manjunath G. Sunagar

2018-03-01

Full Text Available P70-S6K1 & PI3K-δ kinases are identified to be involved in many physiological processes associated with cancer, therefore many of the inhibitors being designed to target these kinases are in clinical trials. In the current study we have exploited the N-9 substituted 6-(4-(4-propoxyphenyl piperazin-1-yl-9H-purine derivatives for their inhibitory properties with the above kinases. We have used an in silico docking study with seventeen purine derivatives for their binding affinity calculations. The binding affinities of these small molecules with P70-S6K1 & PI3K-δ were performed using AutoDock Vina. Among all the compounds, PP16 showed highest binding affinity of −14.7 kcal/mol with P70-S6K1 kinase & −17.2 kcal/mol with PI3K-δ kinases as compared to the molecules under clinical trials (PF-4708671 & IC-87114. Docking studies revealed that N-9 coumarine substituted purine derivative could be one of the potential ligands for the inhibition of P70-S6K1 & PI3K-δ kinases. Hence, this compound can be further investigated by in vitro and in vivo experiments for further validation.

Effect of Am-80, A Novel Retinoid Derivative, On Contact Hypersensitivity Caused by Repeated Applications of Hapten in Mice

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Satoru Niwa

2000-01-01

Full Text Available Some retinoids show an anti-inflammatory action through regulation of transcription of various genes. In the present study, the inhibitory effect of 4-((5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2-naphthyl carbamoyl benzoic acid (Am-80, a synthetic retinoid, on mouse contact hypersensitivity provoked by repeated applications of 2,4-dinitrofluorobenzene (DNFB to the ear was investigated. Five-fold applications of DNFB on ears once per week elicited severe contact dermatitis with marked infiltration of inflammatory cells and elevation of anti-dinitrophenyl (DNP-IgE antibody in the serum. The Am-80 significantly inhibited ear swelling in a dose-dependent manner. In the histopathologic study, infiltration of inflammatory cells was clearly decreased by Am-80. However, Am-80 did not affect the production of DNP-specific IgE antibody both at the transcriptional and post-transcriptional levels. The effects of Am-80 on the transcriptional level of cytokines, interferon (IFN-γ, interleukin (IL-1 and IL-4 in cervical lymph nodes were investigated. Marked elevation of mRNA for all cytokines was observed and Am-80 potently inhibited the expression of IFN-γ mRNA, but not IL-1 and IL-4 mRNA. These findings indicated that Am-80 may inhibit the contact dermatitis at the post-sensitization phase by inhibiting IFN-γ production at the transcriptional level in mice.

Alkaloid-derived molecules in low rank Argonne premium coals.

Energy Technology Data Exchange (ETDEWEB)

Winans, R. E.; Tomczyk, N. A.; Hunt, J. E.

2000-11-30

Molecules that are probably derived from alkaloids have been found in the extracts of the subbituminous and lignite Argonne Premium Coals. High resolution mass spectrometry (HRMS) and liquid chromatography mass spectrometry (LCMS) have been used to characterize pyridine and supercritical extracts. The supercritical extraction used an approach that has been successful for extracting alkaloids from natural products. The first indication that there might be these natural products in coals was the large number of molecules found containing multiple nitrogen and oxygen heteroatoms. These molecules are much less abundant in bituminous coals and absent in the higher rank coals.

Adamantoylated biologically active small peptides and glycopeptides structurally related to the bacterial peptidoglycan.

Science.gov (United States)

Frkanec, Ruža; Vranešić, Branka; Tomić, Srdjanka

2013-01-01

A large number of novel synthetic compounds representing smaller parts of original peptidoglycan molecules have been synthesized and found to possess versatile biological activity, particularly immunomodulating properties. A series of compounds containing the adamantyl residues coupled to peptides and glycopeptides characteristic for bacterial peptidoglycan was described. The new adamantylpeptides and adamantylglycopeptides were prepared starting from N-protected racemic adamantylglycine and dipeptide L-Ala-D-isoglutamine. The adamantyl glycopeptides were obtained by coupling the adamantyltripeptides with alpha-D-mannose moiety through spacer molecule of fixed chirality. Since the starting material was D,L-(adamantyl-glycine) the condensation products with the dipeptide were mixtures of diastereoisomers. The obtained diastereoisomers were separated, characterized, and tested for immunostimulating activity. An HPLC method for purity testing was developed and adapted for the particular compounds.

Effects of Substitutions on the Biodegradation Potential of Benzotriazole Derivatives

Science.gov (United States)

Abu-Dalo, M. A.; O'Brien, I.; Hernandez, M. T.

2018-02-01

Fourteen benzotriazole derivatives were subjected to microcosm tests to study the influence of substitutions on their biodegradation potential. Methylated, nitrated, carboxylated, and propionated bezotriazoles, a heterocyclic triazole, as well as methylated benzimidazoles, were introduced to activated sludge and soil enrichment cultures as the only carbon source. Some of the enrichment cultures were derived from airport soils that had been previously contaminated with aircraft deicing fluids and subsequently enriched with the commercially significant corrosion inhibitor methylbenzotriazole. The 5-methylbenzotriazole and only the carboxylated derivatives were degraded by soil or activated sludge biomass regardless of acclimation conditions. Radiotracer studies of [U-14C] 5-methylbenzotriazole, and [U-14C] 5-carboxybenzotriazole confirmed that relatively high concentrations (25mg L-1) of these derivatives can be completely mineralized in relatively short time frames by microbial consortia regardless of prior exposure. Observations suggested that the growth yield on these compounds is likely low. Biodegradation patterns suggested that carboxylated benzotriazole derivatives are more readily biodegradable than their more popular methylated counterparts.

Excitation and dissociation of molecules by low-energy (0-15 eV) electrons

International Nuclear Information System (INIS)

Verhaart, G.J.

1980-01-01

The author deals with excitation and dissociation processes which result from the interaction between low-energy (0.15 eV) electrons and molecules. Low-energy electron-impact spectroscopy is used to gain a better knowledge of the electronic structure of halomethanes, ethylene and some of its halogen substituted derivatives, and some more complex organic molecules. (Auth.)

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

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Madhuri Vangala

2015-11-01

Full Text Available The TMSOTf-mediated synthesis of β-configured spirocyclic 2-substituted-2-oxazoline ribosides was achieved using a “Ritter-like” reaction in toluene through nucleophilic addition of electron-rich nitriles to the oxacarbenium ion intermediate of 1,2;3,4-di-O-isopropylidene-β-D-psicofuranose derivatives with concomitant intramolecular trapping of the C2 hydroxymethyl group on the electrophilic nitrilium carbon. These carbohydrate-derived spirooxazolines are stable and were obtained in good yield with high stereoselectivity due to the conformational rigidity imparted by the 3,4-isopropylidene group.

Metal borohydrides and derivatives

DEFF Research Database (Denmark)

Paskevicius, Mark; Haarh Jepsen, Lars; Schouwink, Pascal

2017-01-01

major classes of metal borohydride derivatives have also been discovered: anion-substituted compounds where the complex borohydride anion, BH4 -, is replaced by another anion, i.e. a halide or amide ion; and metal borohydrides modified with neutral molecules, such as NH3, NH3BH3, N2H4, etc. Here, we...

Crystallographic characterization of single-ortho, N-substituted acetanilide derivatives

International Nuclear Information System (INIS)

Boeyens, J.C.A.; Denner, L.; Painter, S.; Staskun, B.

1987-01-01

The crystal and molecular structures of the three single-ortho, N-substituted amide derivatives, acet-2'-bromo-N-(p-nitrobenzyl)anilide, 3',5'-dimethyl-N-ethyl-2,2,2',4'-tetrachlorobenzoylacetanilide, and difluoro[(1-phenyl-2-(o-ethylphenyl-N-benzylcarbamoyl)vinyl)oxy]borane, have been determined by X-ray diffraction analysis. In each case, the amide carbonyl group was found in the exo-conformation, independent of the nature of the acyl group. The observed conformations correlate well with solution structures, inferred from n.m.r. data

Subpicosecond pulse radiolysis in liquid methyl-substituted benzene derivatives

International Nuclear Information System (INIS)

Okamoto, Kazumasa; Kozawa, Takahiro; Saeki, Akinori; Yoshida, Yoichi; Tagawa, Seiichi

2007-01-01

The early processes of radiation chemistry in the picosecond time region in methyl-substituted benzene derivatives have been investigated using subpicosecond pulse radiolysis. In o-xylene, a fairly slow geminate ion recombination was observed within 50 ps after the electron beam irradiation; this is due to the smaller electron mobility. The kinetic traces were analyzed using the Smoluchowski equation with exponential and modified-Gaussian (YGP) functions as the distribution of thermalized electrons. Only exponential functions well reproduced the experimental data within 50 ps after the electron pulse

Retinoids: literature review and suggested algorithm for use prior to facial resurfacing procedures

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Patrick J Buchanan

2016-01-01

Full Text Available Vitamin A-containing products have been used topically since the early 1940s to treat various skin conditions. To date, there are four generations of retinoids, a family of Vitamin A-containing compounds. Tretinoin, all-trans-retinoic acid, is a first-generation, naturally occurring, retinoid. It is available, commercially, as a gel or cream. The authors conducted a complete review of all studies, clinical- and basic science-based studies, within the literature involving tretinoin treatment recommendations for impending facial procedures. The literature currently lacks definitive recommendations for the use of tretinoin-containing products prior to undergoing facial procedures. Tretinoin pretreatment regimens vary greatly in terms of the strength of retinoid used, the length of the pre-procedure treatment, and the ideal time to stop treatment before the procedure. Based on the current literature and personal experience, the authors set forth a set of guidelines for the use of tretinoin prior to various facial procedures.

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

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NALILU SUCHETHA KUMARI

2011-02-01

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

Synthesis and Cytotoxicity of Novel Hexahydrothienocycloheptapyridazinone Derivatives

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Irene Marchesi

2009-09-01

Full Text Available Designed as a new group of tricyclic molecules containing the thienocycloheptapyridazinone ring system, a number of 2N-substituted-hexahydrothienocycloheptapyridazinone derivatives were synthesized and their biological activity evaluated. Among the synthesized compounds, derivatives 7d and 7h were found to possess cytotoxic activity against non-small cell lung cancer and central nervous system cancer cell lines, respectively.

Copper-catalyzed aerobic oxidative C-H functionalization of substituted pyridines: synthesis of imidazopyridine derivatives.

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Yu, Jipan; Jin, Yunhe; Zhang, Hao; Yang, Xiaobo; Fu, Hua

2013-12-02

A novel, efficient, and practical method for the synthesis of imidazopyridine derivatives has been developed through the copper-catalyzed aerobic oxidative C-H functionalization of substituted pyridines with N-(alkylidene)-4H-1,2,4-triazol-4-amines. The procedure occurs by cleavage of the N-N bond in the N-(alkylidene)-4H-1,2,4-triazol-4-amines and activation of an aryl C-H bond in the substituted pyridines. This is the first example of the preparation of imidazopyridine derivatives by using pyridines as the substrates by transition-metal-catalyzed C-H functionalization. This method should provide a novel and efficient strategy for the synthesis of other nitrogen heterocycles. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A new class of synthetic retinoid antibiotics effective against bacterial persisters.

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Kim, Wooseong; Zhu, Wenpeng; Hendricks, Gabriel Lambert; Van Tyne, Daria; Steele, Andrew D; Keohane, Colleen E; Fricke, Nico; Conery, Annie L; Shen, Steven; Pan, Wen; Lee, Kiho; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Vlahovska, Petia M; Wuest, William M; Gilmore, Michael S; Gao, Huajian; Ausubel, Frederick M; Mylonakis, Eleftherios

2018-04-05

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant 'persister' subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

A new class of synthetic retinoid antibiotics effective against bacterial persisters

Science.gov (United States)

Kim, Wooseong; Zhu, Wenpeng; Hendricks, Gabriel Lambert; van Tyne, Daria; Steele, Andrew D.; Keohane, Colleen E.; Fricke, Nico; Conery, Annie L.; Shen, Steven; Pan, Wen; Lee, Kiho; Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Vlahovska, Petia M.; Wuest, William M.; Gilmore, Michael S.; Gao, Huajian; Ausubel, Frederick M.; Mylonakis, Eleftherios

2018-04-01

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant ‘persister’ subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans–MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

Molecular-weight-enlarged multiple-pincer ligands: synthesis and application in palladium-catalyzed allylic substitution reactions

NARCIS (Netherlands)

Ronde, N.J.; Totev, D.; Müller, Christian; Lutz, M.; Spek, A.L.; Vogt, D.

2009-01-01

Three different pincer ligand systems are synthesized via nucleophilic substitution reactions of polyaromatic benzyl bromides as support molecules and phenol derivatives as ligand precursors. Retention tests using a polymeric nanofiltration membrane show moderate to good retention in THF and CH2Cl2.

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

Science.gov (United States)

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

2015-01-01

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

Retinoid-induced expression and activity of an immediate early tumor suppressor gene in vascular smooth muscle cells.

Directory of Open Access Journals (Sweden)

Jeffrey W Streb

2011-04-01

Full Text Available Retinoids are used clinically to treat a number of hyper-proliferative disorders and have been shown in experimental animals to attenuate vascular occlusive diseases, presumably through nuclear receptors bound to retinoic acid response elements (RARE located in target genes. Here, we show that natural or synthetic retinoids rapidly induce mRNA and protein expression of a specific isoform of A-Kinase Anchoring Protein 12 (AKAP12β in cultured smooth muscle cells (SMC as well as the intact vessel wall. Expression kinetics and actinomycin D studies indicate Akap12β is a retinoid-induced, immediate-early gene. Akap12β promoter analyses reveal a conserved RARE mildly induced with atRA in a region that exhibits hyper-acetylation. Immunofluorescence microscopy and protein kinase A (PKA regulatory subunit overlay assays in SMC suggest a physical association between AKAP12β and PKA following retinoid treatment. Consistent with its designation as a tumor suppressor, inducible expression of AKAP12β attenuates SMC growth in vitro. Further, immunohistochemistry studies establish marked decreases in AKAP12 expression in experimentally-injured vessels of mice as well as atheromatous lesions in humans. Collectively, these results demonstrate a novel role for retinoids in the induction of an AKAP tumor suppressor that blocks vascular SMC growth thus providing new molecular insight into how retiniods may exert their anti-proliferative effects in the injured vessel wall.

Retinoid inhibition of in vitro invasion of human amnion basement membrane by human tumor cells

International Nuclear Information System (INIS)

Fazely, F.

1988-01-01

The effects measured were the inhibition of tumor cell migration through the basement membrane (BM) and tumor cell degradative enzyme activity on 3 H-proline labeled collagenous and non collagenous components of the BM. The human lung carcinoma A549 or the human Ewing's sarcoma TC-106 cell lines treated with retinoids for two days were incubated on the BM in the absence of retinoids. A dose-dependent inhibition of cell invasion was produced by retinoids. Among the retinoids tested the most powerful was retinol acetate which inhibited invasion by 50% of A549 cells at a concentration of 0.09 μg/ml, and TC-106 cells at 0.08 μg/ml. Retinol acetate inhibited A549 and TC-106 cell growth by approximately 50% at levels almost 100-fold higher than those needed for antiinvasive activity. Retinol acetate was about 20 times more potent than retinoic acid and 30 times more than retinol palmitate. Furthermore, A549 cells treated with retinol acetate, under conditions whereby an anti-invasive state was induced,showed an increase in the number of cellular retinoic acid binding proteins (CRABP), a decrease in the activity of type IV collagenase and ectosialyltransferase, and no change in the activity of transglutaminase

Single Molecule Conductance of Oligothiophene Derivatives

Science.gov (United States)

Dell, Emma J.

This thesis studies the electronic properties of small organic molecules based on the thiophene motif. If we are to build next-generation devices, advanced materials must be designed which possess requisite electronic functionality. Molecules present attractive candidates for these ad- vanced materials since nanoscale devices are particularly sought after. However, selecting a molecule that is suited to a certain electronic function remains a challenge, and characterization of electronic behavior is therefore critical. Single molecule conductance measurements are a powerful tool to determine properties on the nanoscale and, as such, can be used to investigate novel building blocks that may fulfill the design requirements of next-generation devices. Combining these conductance results with strategic chemical synthesis allows for the development of new families of molecules that show attractive properties for future electronic devices. Since thiophene rings are the fruitflies of organic semiconductors on the bulk scale, they present an intriguing starting point for building functional materials on the nanoscale, and therefore form the structural basis of all molecules studied herein. First, the single-molecule conductance of a family of bithiophene derivatives was measured. A broad distribution in the single-molecule conductance of bithiophene was found compared with that of a biphenyl. This increased breadth in the conductance distribution was shown to be explained by the difference in 5-fold symmetry of thiophene rings as compared to the 6-fold symmetry of benzene rings. The reduced symmetry of thiophene rings results in a restriction on the torsion angle space available to these molecules when bound between two metal electrodes in a junction, causing each molecular junction to sample a different set of conformers in the conductance measurements. By contrast, the rotations of biphenyl are essentially unimpeded by junction binding, allowing each molecular junction

Synthesis and Fungicidal activity of some sulphide derivatives of O-Ethyl-N-substituted phenylcarbamates

International Nuclear Information System (INIS)

Imeokparia, F.A.

2006-01-01

Monosulphides of O-ethyl-N-substituted phenylcarbamates were prepared by the reaction between O-ethyl-N-substituted phenylcarbamates and sulphur dichloride, while the corresponding disulphides were prepared by the reaction between O-ethyl-N-substituted phenylcarbamates and sulphur monochloride. The synthesized compounds were characterized by elemental analysis, thin layer chromatography (TLC), Fourier-transform infrared, and /sup 1/H and /sup 13/C nuclear magnetic resonance spectroscopic techniques. In vitro fungicidal assay of these sulphides against Fusarium oxysporum, Aspergillus niger, Aspergillus flavus and Rhizopus stolonifer showed that they had Greater fungicidal activity than their parent carbamates. The synthesized sulphides were more active towards A. Niger and A. flavus. Unlike the parent carbamates, the type of substituents attached to the aromatic nucleus of these sulphides had little or no effect on their fungicidal activity as there was insignificant variation in the fungicidal activity of the monosulphide and the disulphide derivatives of O-ethyl-N-substituted phenylcarbamates. (author)

MHC class II-derived peptides can bind to class II molecules, including self molecules, and prevent antigen presentation

DEFF Research Database (Denmark)

Rosloniec, E F; Vitez, L J; Buus, S

1990-01-01

the alpha k-3 peptide binds slightly less well. These combined data, suggesting that class II-derived peptides can bind to MHC class II molecules, including the autologous molecule from which they are derived, have important implications for the molecular basis of alloreactivity and autoreactivity. Further...... found in the first and third polymorphic regions (PMR) of the A alpha k chain (alpha k-1 and alpha k-3) were capable of inhibiting the presentation of three different HEL-derived peptide antigens to their appropriate T cells. In addition, the alpha k-1 peptide inhibited the presentation of the OVA(323......-339) immunodominant peptide to the I-Ad-restricted T cell hybridomas specific for it. Prepulsing experiments demonstrated that the PMR peptides were interacting with the APC and not with the T cell hybridomas. These observations were confirmed and extended by the demonstration that the alpha k-1 and alpha k-3...

Chemical Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with Substituted Amino Moiety

Science.gov (United States)

Shang, Ruofeng; Wang, Shengyu; Xu, Ximing; Yi, Yunpeng; Guo, Wenzhu; YuLiu; Liang, Jianping

2013-01-01

Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC) of 23S rRNA. PMID:24376551

Chemical synthesis and biological activities of novel pleuromutilin derivatives with substituted amino moiety.

Directory of Open Access Journals (Sweden)

Ruofeng Shang

Full Text Available Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC of 23S rRNA.

Substitution pattern elucidation of hydroxypropyl Pinus pinaster (Ait.) bark polyflavonoid derivatives by ESI(-)-MS/MS.

Science.gov (United States)

García Marrero, Danny E; Glasser, Wolfgang G; Pizzi, Antonio; Paczkowski, Sebastian; Laborie, Marie-Pierre G

2014-10-01

The structure of condensed tannins (CTs) from Pinus pinaster bark extract and their hydroxypropylated derivatives with four degrees of substitution (DS 1, 2, 3 and 4) has been characterized for the first time using negative-ion mode electrospray ionization tandem mass spectrometry (ESI(-)-MS/MS). The results showed that P. pinaster bark CTs possess structural homogeneity in terms of monomeric units (C(15), catechin). The oligomer sizes were detected to be dimers to heptamers. The derivatives showed typical phenyl-propyl ether mass fragmentation by substituent elimination (58 amu) and inherent C(15) flavonoid fissions. The relative abundance of the product ions revealed a preferential triple, tetra-/penta- and octa- hydroxypropylation substitution pattern in the monomer, dimer and trimer derivatives, respectively. A defined order of -OH reactivity towards propylene oxide was established by means of multistage experiments (A-ring ≥ B-ring > C-ring). A high structural heterogeneity of the modified oligomers was detected. Copyright © 2014 John Wiley & Sons, Ltd.

CASTING A BROAD NETWORK: FISHING FOR MECHANISMS OF RETINOID TERATOGENICITY

Science.gov (United States)

This is a short essay that serves to introduce a featured paper for an issue of Toxicological Sciences. The paper being introduced describes a study of mechanisms of retinoid induced abnormal limb development in mice. The paper was notable because the authors used gene expressi...

The neurobehavioral teratology of retinoids: a 50-year history.

Science.gov (United States)

Adams, Jane

2010-10-01

This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

The formation of [M-H]+ ions in N-alkyl-substituted thieno[3,4-c]-pyrrole-4,6-dione derivatives during atmospheric pressure photoionization mass spectrometry

KAUST Repository

Sioud, Salim

2014-10-09

RESULTS [M-H]+ ions were observed under APPI conditions. The type of dopant and the length of the alkyl chain affected the formation of these ions. MS/MS fragmentation of [M-H]+ and [M + H]+ ions exhibited completely different patterns. Theoretical calculations revealed that the loss of hydrogen molecules from the [M + H]+ ions is the most favourable condition under which to form [M-H]+ ions.CONCLUSIONS [M-H]+ ions were detected in all the TPD derivatives studied here under the special experimental conditions during APPI, using a halogenated benzene dopant, and TPD containing substituted N-alkyl side chains with a minimum of four carbon atoms. Density functional theory calculations showed that for [M-H]+ ions to be formed under these conditions, the loss of hydrogen molecules from the [M + H]+ ions is proposed to be necessary.RATIONALE The formation of ions during atmospheric pressure photoionization (APPI) mass spectrometry in the positive mode usually provides radical cations and/or protonated species. Intriguingly, during the analysis of some N-alkyl-substituted thieno[3,4-c]pyrrole-4,6-dione (TPD) derivatives synthesized in our laboratory, unusual [M-H]+ ion peaks were observed. In this work we investigate the formation of [M-H]+ ions observed under APPI conditions.METHODS Multiple experimental parameters, including the type of ionization source, the composition of the solvent, the type of dopant, the infusion flow rate, and the length of the alkyl side chain were investigated to determine their effects on the formation of [M-H]+ ions. In addition, a comparison study of the gas-phase tandem mass spectrometric (MS/MS) fragmentation of [M + H]+ vs [M-H]+ ions and computational approaches were used.

Exohedral and skeletal rearrangements in the molecules of fullerene derivatives

Energy Technology Data Exchange (ETDEWEB)

Ignat' eva, Daria V; Ioffe, I N; Troyanov, Sergey I; Sidorov, Lev N [Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow (Russian Federation)

2011-07-31

The data on the migration of monoatomic addends, perfluoroalkyl and more complex organic groups in the molecules of fullerene derivatives published mainly in the last decade are analyzed. Skeletal rearrangements of the carbon cage occurring during chemical reactions are considered.

Synthesis and Analgesic Activity of Novel Derivatives of 1,2-Substituted Benzimidazoles

Directory of Open Access Journals (Sweden)

Shobhit Srivastava

2013-01-01

Full Text Available A series of novel 2-phenylhydrazinomethyl and 2-(2-hydroxyphenyl-benzimidazole derivatives substituted at the N1-position of benzimidazole nucleus were synthesized as well as screened for analgesic activity. Some of these compounds showed promising analgesic activity when compared with the standard drug diclofenac sodium. The incorporation of a phenylhydrazinomethyl nucleus at 2-position of benzimidazole compound gave a biologically active pharmacophore.

Toward precise potential energy curves for diatomic molecules, derived from experimental line positions

International Nuclear Information System (INIS)

Helm, H.

1984-01-01

An inverted, first-order perturbation approach is used to derive potential energy curves for diatomic molecules from experimental line positions of molecular bands. The concept adopted here is based on the inverted perturbation analysis (IPA) proposed by Kozman and Hinze, but uses radial eigenfunctions of the trial potential energy curves as basis sets for the perturbation correction. Using molecular linepositions rather than molecular energy levels we circumvent the necessity of defining molecular constants for the molecule prior to the derivation of the potential energy curves. (Author)

Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.

Science.gov (United States)

Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki

2017-03-01

Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

UV action spectroscopy of protonated PAH derivatives. Methyl substituted quinolines

DEFF Research Database (Denmark)

Klærke, Benedikte; Holm, Anne; Andersen, Lars Henrik

2011-01-01

using the electrostatic storage ring ELISA, an electrospray ion source and 3 ns UV laser pulses. Results. It is shown that the absorption profile is both redshifted and broadened when moving the methyl group from the heterocycle containing nitrogen to the homoatomic ring. The absorption profiles......Aims. We investigate the production of molecular photofragments upon UV excitation of PAH derivatives, relevant for the interstellar medium. Methods. The action absorption spectra of protonated gas-phase methyl-substituted quinolines (CH3−C9H7NH+) have been recorded in the 215–338 nm spectral range...

Photovoltaic Small Molecules of TPA(FxBT-T-Cz)3: Tuning Open-Circuit Voltage over 1.0 V for Their Organic Solar Cells by Increasing Fluorine Substitution.

Science.gov (United States)

Wang, Qiong; Duan, Linrui; Tao, Qiang; Peng, Wenhong; Chen, Jianhua; Tan, Hua; Yang, Renqiang; Zhu, Weiguo

2016-11-09

To simultaneously improve both open-circuit voltage (V oc ) and short-circuit current density (J sc ) for organic solar cells, a novel D(A-π-Ar) 3 type of photovoltaic small molecules of TPA(F x BT-T-3Cz) 3 was designed and synthesized, which contain central triphenylamine (TPA), terminal carbazole (Cz), armed fluorine-substituted benzothiadiazole (F x BT, where x = 1 or 2), and bridged thiophene (T) units. A narrowed ultraviolet-visible absorption and a decreasing highest occupied molecular orbital energy level were observed from TPA(F 1 BT-T-3Cz) 3 to TPA(F 2 BT-T-3Cz) 3 with increasing fluorine substitution. However, the TPA(F 2 BT-T-3Cz) 3 /PC 71 BM-based solar devices showed a rising V oc of 1.01 V and an enhanced J sc of 10.84 mA cm -2 as well as a comparable power conversion efficiency of 4.81% in comparison to the TPA(F 1 BT-T-3Cz) 3 /PC 71 BM-based devices. Furthermore, in comparison to the parent TPA(BT-T-3Cz) 3 molecule without fluorine substitution, the fluorine-substituted TPA(F x BT-T-3Cz) 3 molecules exhibited significantly incremental V oc and J sc values in their bulk heterojunction organic solar cells, owing to fluorine incorporation in the electron-deficient benzothiadiazole unit.

Consequences of the natural retinoid/retinoid X receptor ligands action in human breast cancer MDA-MB-231 cell line: Focus on functional proteomics

Czech Academy of Sciences Publication Activity Database

Flodrová, Dana; Toporová, L.; Laštovičková, Markéta; Macejová, D.; Hunaková, L.; Brtko, J.; Bobálová, Janette

2017-01-01

Roč. 281, NOV (2017), s. 26-34 ISSN 0378-4274 R&D Projects: GA ČR(CZ) GA15-15479S Grant - others:AV ČR(CZ) SAV-15-01 Program:Bilaterální spolupráce Institutional support: RVO:68081715 Keywords : breast cancer * MDA-MB-231 * biomarker * retinoids Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 3.858, year: 2016

Singlet Oxygen and Free Radical Reactions of Retinoids and Carotenoids—A Review

Science.gov (United States)

Truscott, T. George

2018-01-01

We report on studies of reactions of singlet oxygen with carotenoids and retinoids and a range of free radical studies on carotenoids and retinoids with emphasis on recent work, dietary carotenoids and the role of oxygen in biological processes. Many previous reviews are cited and updated together with new data not previously reviewed. The review does not deal with computational studies but the emphasis is on laboratory-based results. We contrast the ease of study of both singlet oxygen and polyene radical cations compared to neutral radicals. Of particular interest is the switch from anti- to pro-oxidant behavior of a carotenoid with change of oxygen concentration: results for lycopene in a cellular model system show total protection of the human cells studied at zero oxygen concentration, but zero protection at 100% oxygen concentration. PMID:29301252

Synthesis of Various Polyaniline / Clay Nanocomposites Derived from Aniline and Substituted Aniline Derivatives by Mechanochemical Intercalation Method

Directory of Open Access Journals (Sweden)

N. Kalaivasan

2010-01-01

Full Text Available Polyaniline clay nanocomposite can be prepared by mechano-chemical method in which intercalation of anilinium ion into the clay lattices accomplished by mechanical grinding of sodium montmorillonite (Na+MMT in presence of anilinium hydrochloride at room temperature using mortar & pestle for about 30 min and subsequent grinding with oxidizing agent, ammonium peroxysulfate. The appearance of green colour indicates the formation of polyaniline/clay nanocomposite (PANI/Clay. Similarly aniline derivatives like o-toludine and o-anisidine in the form of HCl salt can form intercalation into the clay lattices. The intercalated aniline derivatives were ground mechanically in presence of oxidizing agent ammonium peroxysulfate lead to formation of substituted polyaniline/ clay nanocomposites. The characteristics of various polyaniline-clay nanocomposites were investigated using UV-Visible, FT-IR, cyclic voltammetry studies.

Evaluation of substituted ebselen derivatives as potential trypanocidal agents.

Science.gov (United States)

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

2017-02-01

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

Synthetic Methods and Exploring Biological Potential of Various Substituted Quinoxalin-2-one Derivatives

OpenAIRE

Mohammad Asif

2016-01-01

Substituted quinoxaline have considerable interest in chemistry, biology and pharmacology. Quinoxaline derivatives are capable with variety of biological activities and possess different biological activities, of which the most potent are anti-microbial, analgesic and anti-inflammatory activities. It facilitated the researchers to develop various methods for their synthesis and their applications. In this review represented different methods of synthesis, reactivity and various biological act...

Correction: Synthesis of pyrrolidine-3-carboxylic acid derivatives via asymmetric Michael addition reactions of carboxylate-substituted enones.

Science.gov (United States)

Yin, Feng; Garifullina, Ainash; Tanaka, Fujie

2018-04-25

Correction for 'Synthesis of pyrrolidine-3-carboxylic acid derivatives via asymmetric Michael addition reactions of carboxylate-substituted enones' by Feng Yin et al., Org. Biomol. Chem., 2017, 15, 6089-6092.

DFT, FT-IR, FT-Raman and NMR studies of 4-(substituted phenylazo)-3,5-diacetamido-1H-pyrazoles

Science.gov (United States)

Kınalı, Selin; Demirci, Serkan; Çalışır, Zühre; Kurt, Mustafa; Ataç, Ahmet

2011-05-01

We present a detailed analysis of the structural and vibrational spectra of some novel azo dyes. 2-(Substituted phenylazo)malononitriles were synthesized by the coupling reaction of the diazonium salts, which were prepared with the use of various aniline derivatives with malononitrile, and then 4-(substituted phenylazo)-3,5-diamino-1H-pyrazole azo dyes were obtained via the ring closure of the azo compounds with hydrazine monohydrate. The experimental and theoretical vibrational spectra of azo dyes were studied. The structural and spectroscopic analysis of the molecules were carried out by using Becke's three-parameters hybrid functional (B3LYP) and density functional harmonic calculations. The 1H nuclear magnetic resonance (NMR) chemical shifts of the azo dye molecules were calculated using the gauge-invariant-atomic orbital (GIAO) method. The calculated vibrational wavenumbers and chemical shifts were compared with the experimental data of the molecules.

Surface modified liposomes by mannosylated conjugates anchored via the adamantyl moiety in the lipid bilayer.

Science.gov (United States)

Stimac, Adela; Segota, Suzana; Dutour Sikirić, Maja; Ribić, Rosana; Frkanec, Leo; Svetličić, Vesna; Tomić, Srđanka; Vranešić, Branka; Frkanec, Ruža

2012-09-01

The aim of the present study was to encapsulate mannosylated 1-aminoadamantane and mannosylated adamantyltripeptides, namely [(2R)-N-(adamant-1-yl)-3-(α,β-d-mannopyranosyloxy)-2-methylpropanamide and (2R)-N-[3-(α-d-mannopyranosyloxy)-2-methylpropanoyl]-d,l-(adamant-2-yl)glycyl-l-alanyl-d-isoglutamine] in liposomes. The characterization of liposomes, size and surface morphology was performed using dynamic light scattering (DLS) and atomic force microscopy (AFM). The results have revealed that the encapsulation of examined compounds changes the size and surface of liposomes. After the concanavalin A (ConA) was added to the liposome preparation, increase in liposome size and their aggregation has been observed. The enlargement of liposomes was ascribed to the specific binding of the ConA to the mannose present on the surface of the prepared liposomes. Thus, it has been shown that the adamantyl moiety from mannosylated 1-aminoadamantane and mannosylated adamantyltripeptides can be used as an anchor in the lipid bilayer for carbohydrate moiety exposed on the liposome surface. Copyright © 2012 Elsevier B.V. All rights reserved.

Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest.

Science.gov (United States)

Duran, Leidy Tatiana Díaz; Rincón, Nathalia Olivar; Galvis, Carlos Eduardo Puerto; Kouznetsov, Vladimir V; Lorenzo, Jorge Luis Fuentes

2015-03-01

Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure-genotoxicity relationships and bioassay-guided quinoline synthesis. © 2013 Wiley Periodicals, Inc.

Isotope chirality in long-armed multifunctional organosilicon ("Cephalopod") molecules.

Science.gov (United States)

Barabás, Béla; Kurdi, Róbert; Zucchi, Claudia; Pályi, Gyula

2018-07-01

Long-armed multifunctional organosilicon molecules display self-replicating and self-perfecting behavior in asymmetric autocatalysis (Soai reaction). Two representatives of this class were studied by statistical methods aiming at determination of probabilities of natural abundance chiral isotopomers. The results, reported here, show an astonishing richness of possibilities of the formation of chiral isotopically substituted derivatives. This feature could serve as a model for the evolution of biological chirality in prebiotic and early biotic stereochemistry. © 2018 Wiley Periodicals, Inc.

Design, synthesis and inhibitory activities of 8-(substituted styrol-formamido)phenyl-xanthine derivatives on monoamine oxidase B.

Science.gov (United States)

Hu, Suwen; Nian, Siyun; Qin, Kuiyou; Xiao, Tong; Li, Lingna; Qi, Xiaolu; Ye, Faqing; Liang, Guang; Hu, Guoxin; He, Jincai; Yu, Yinfei; Song, Bo

2012-01-01

The design and synthesis of two series of 8-(substituted styrol-formamido)phenyl-xanthine derivatives are described. Their in vitro monoamine oxidase B (MAO-B) inhibition were tested and the effect of substituents on the N-7, phenyl and the substituted positions are discussed. It was observed that compound 9b displayed significant MAO-B inhibition activity and selectivity, fluorine substitution plays a key role in the selectivity of MAO-B inhibition, and the styrol-formamido group at position-3' may enhance the activity and selectivity of 8-phenyl-xanthine analogues. These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for treatment of Parkinson's disease.

Design of ortho-Substituted Donor-Acceptor Molecules as Highly Efficient Green Thermally Activated Delayed Fluorescent Emitters

Science.gov (United States)

Cha, Jae-Ryung; Gong, Myoung-Seon; Lee, Tak Jae; Ha, Tae Hoon; Lee, Chil Won

2018-04-01

The ortho-substituted donor-acceptor molecules 2-(4,6-diphenyl-1, 3, 5-triazin-2-yl)- N,Ndiphenylaniline (DPA- o-Trz) and 2-(4,6-diphenyl-1, 3, 5-triazine-2-yl)- N,N-di- p-tolylaniline (MPA- o-Trz) were designed, synthesized, and found to exhibit green fluorescence characteristics. Notably, the singlet-triplet energy gap was less than 0.1 eV, indicating that reverse intersystem crossing gave rise to thermally activated delayed fluorescence (TADF). The organic light-emitting device performance of MPA- o-Trz showed a high external quantum efficiency of 16.3% and good color stability from 0.1 cd/m2 to 5000 cd/m2.

Aryl substitution of pentacenes

Directory of Open Access Journals (Sweden)

Andreas R. Waterloo

2014-07-01

Full Text Available A series of 11 new pentacene derivatives has been synthesized, with unsymmetrical substitution based on a trialkylsilylethynyl group at the 6-position and various aryl groups appended to the 13-position. The electronic and physical properties of the new pentacene chromophores have been analyzed by UV–vis spectroscopy (solution and thin films, thermoanalytical methods (DSC and TGA, cyclic voltammetry, as well as X-ray crystallography (for 8 derivatives. X-ray crystallography has been specifically used to study the influence of unsymmetrical substitution on the solid-state packing of the pentacene derivatives. The obtained results add to our ability to better predict substitution patterns that might be helpful for designing new semiconductors for use in solid-state devices.

Aryl substitution of pentacenes

Science.gov (United States)

Waterloo, Andreas R; Sale, Anna-Chiara; Lehnherr, Dan; Hampel, Frank

2014-01-01

Summary A series of 11 new pentacene derivatives has been synthesized, with unsymmetrical substitution based on a trialkylsilylethynyl group at the 6-position and various aryl groups appended to the 13-position. The electronic and physical properties of the new pentacene chromophores have been analyzed by UV–vis spectroscopy (solution and thin films), thermoanalytical methods (DSC and TGA), cyclic voltammetry, as well as X-ray crystallography (for 8 derivatives). X-ray crystallography has been specifically used to study the influence of unsymmetrical substitution on the solid-state packing of the pentacene derivatives. The obtained results add to our ability to better predict substitution patterns that might be helpful for designing new semiconductors for use in solid-state devices. PMID:25161729

Packing and Disorder in Substituted Fullerenes

KAUST Repository

Tummala, Naga Rajesh

2016-07-15

Fullerenes are ubiquitous as electron-acceptor and electron-transport materials in organic solar cells. Recent synthetic strategies to improve the solubility and electronic characteristics of these molecules have translated into a tremendous increase in the variety of derivatives employed in these applications. Here, we use molecular dynamics (MD) simulations to examine the impact of going from mono-adducts to bis- and tris-adducts on the structural, cohesive, and packing characteristics of [6,6]-phenyl-C60-butyric acid methyl ester (PCBM) and indene-C60. The packing configurations obtained at the MD level then serve as input for density functional theory calculations that examine the solid-state energetic disorder (distribution of site energies) as a function of chemical substitution. The variations in structural and site-energy disorders reflect the fundamental materials differences among the derivatives and impact the performance of these materials in thin-film electronic devices.

Substituent effects on the electronic characteristics of pentacene derivatives for organic electronic devices: dioxolane-substituted pentacene derivatives with triisopropylsilylethynyl functional groups.

Science.gov (United States)

Griffith, Olga Lobanova; Anthony, John E; Jones, Adolphus G; Shu, Ying; Lichtenberger, Dennis L

2012-08-29

The intramolecular electronic structures and intermolecular electronic interactions of 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS pentacene), 6,14-bis-(triisopropylsilylethynyl)-1,3,9,11-tetraoxa-dicyclopenta[b,m]-pentacene (TP-5 pentacene), and 2,2,10,10-tetraethyl-6,14-bis-(triisopropylsilylethynyl)-1,3,9,11-tetraoxa-dicyclopenta[b,m]pentacene (EtTP-5 pentacene) have been investigated by the combination of gas-phase and solid-phase photoelectron spectroscopy measurements. Further insight has been provided by electrochemical measurements in solution, and the principles that emerge are supported by electronic structure calculations. The measurements show that the energies of electron transfer such as the reorganization energies, ionization energies, charge-injection barriers, polarization energies, and HOMO-LUMO energy gaps are strongly dependent on the particular functionalization of the pentacene core. The ionization energy trends as a function of the substitution observed for molecules in the gas phase are not reproduced in measurements of the molecules in the condensed phase due to polarization effects in the solid. The electronic behavior of these materials is impacted less by the direct substituent electronic effects on the individual molecules than by the indirect consequences of substituent effects on the intermolecular interactions. The ionization energies as a function of film thickness give information on the relative electrical conductivity of the films, and all three molecules show different material behavior. The stronger intermolecular interactions in TP-5 pentacene films lead to better charge transfer properties versus those in TIPS pentacene films, and EtTP-5 pentacene films have very weak intermolecular interactions and the poorest charge transfer properties of these molecules.

SerpentinaDB: a database of plant-derived molecules of Rauvolfia serpentina.

Science.gov (United States)

Pathania, Shivalika; Ramakrishnan, Sai Mukund; Randhawa, Vinay; Bagler, Ganesh

2015-08-04

Plant-derived molecules (PDMs) are known to be a rich source of diverse scaffolds that could serve as a basis for rational drug design. Structured compilation of phytochemicals from traditional medicinal plants can facilitate prospection for novel PDMs and their analogs as therapeutic agents. Rauvolfia serpentina is an important medicinal plant, endemic to Himalayan mountain ranges of Indian subcontinent, reported to be of immense therapeutic value against various diseases. We present SerpentinaDB, a structured compilation of 147 R. serpentina PDMs, inclusive of their plant part source, chemical classification, IUPAC, SMILES, physicochemical properties, and 3D chemical structures with associated references. It also provides refined search option for identification of analogs of natural molecules against ZINC database at user-defined cut-off. SerpentinaDB is an exhaustive resource of R. serpentina molecules facilitating prospection for therapeutic molecules from a medicinally important source of natural products. It also provides refined search option to explore the neighborhood of chemical space against ZINC database to identify analogs of natural molecules obtained as leads. In a previous study, we have demonstrated the utility of this resource by identifying novel aldose reductase inhibitors towards intervention of complications of diabetes.

Prevention of UV irradiation induced suppression of monocyte functions by retinoids and carotenoids in vitro

International Nuclear Information System (INIS)

Schoen, D.J.; Watson, R.R.

1988-01-01

The effects of stimulation of human peripheral blood monocytes in vitro with retinoids and carotenoids, and subsequent exposure to ultraviolet light of the B wavelength were measured. The compounds were applied to the monocytes in culture for 24 h, and the washed cells were then exposed to UVB light up to 220 J/m 2 . The compounds tested protected the monocyte from UVB induced damage to phagocytic activity. This protection may be due to the antioxidant or UVB energy-quenching properties of these compounds. Monocyte cytotoxicity against a melanoma cell line was stimulated by exposure to the retinoids or carotenoids, but a protective effect in vitro against UVB damage was not seen for this cell function. (author)

Integrating protein structures and precomputed genealogies in the Magnum database: Examples with cellular retinoid binding proteins

Directory of Open Access Journals (Sweden)

Bradley Michael E

2006-02-01

Full Text Available Abstract Background When accurate models for the divergent evolution of protein sequences are integrated with complementary biological information, such as folded protein structures, analyses of the combined data often lead to new hypotheses about molecular physiology. This represents an excellent example of how bioinformatics can be used to guide experimental research. However, progress in this direction has been slowed by the lack of a publicly available resource suitable for general use. Results The precomputed Magnum database offers a solution to this problem for ca. 1,800 full-length protein families with at least one crystal structure. The Magnum deliverables include 1 multiple sequence alignments, 2 mapping of alignment sites to crystal structure sites, 3 phylogenetic trees, 4 inferred ancestral sequences at internal tree nodes, and 5 amino acid replacements along tree branches. Comprehensive evaluations revealed that the automated procedures used to construct Magnum produced accurate models of how proteins divergently evolve, or genealogies, and correctly integrated these with the structural data. To demonstrate Magnum's capabilities, we asked for amino acid replacements requiring three nucleotide substitutions, located at internal protein structure sites, and occurring on short phylogenetic tree branches. In the cellular retinoid binding protein family a site that potentially modulates ligand binding affinity was discovered. Recruitment of cellular retinol binding protein to function as a lens crystallin in the diurnal gecko afforded another opportunity to showcase the predictive value of a browsable database containing branch replacement patterns integrated with protein structures. Conclusion We integrated two areas of protein science, evolution and structure, on a large scale and created a precomputed database, known as Magnum, which is the first freely available resource of its kind. Magnum provides evolutionary and structural

Effect of a bulky lateral substitution by chlorine atom and methoxy group on self-assembling properties of lactic acid derivatives

Czech Academy of Sciences Publication Activity Database

Stojanović, M.; Bubnov, Alexej; Obadović, D.Ž.; Hamplová, Věra; Cvetinov, M.; Kašpar, Miroslav

2014-01-01

Roč. 146, 1-2 (2014), s. 18-25 ISSN 0254-0584 R&D Projects: GA ČR GA13-14133S Grant - others:AVČR(CZ) M100101204 Institutional support: RVO:68378271 Keywords : ferroelectric liquid crystal * lactic acid derivative * lateral substitution * methoxy group * chlorine substitution * dielectric spectroscopy Subject RIV: JJ - Other Materials Impact factor: 2.259, year: 2014

Substituted group and side chain effects for the porphyrin and zinc(II)–porphyrin derivatives: A DFT and TD-DFT study

International Nuclear Information System (INIS)

Tai, Chin-Kuen; Chuang, Wen-Hua; Wang, Bo-Cheng

2013-01-01

The DFT/B3LYP/LANL2DZ and TD-DFT calculations have been performed to generate the optimized structures, electronic and photo-physical properties for the porphyrin and zinc(II)–porphyrin (metalloporphyrin) derivatives. The substituted group and side chain effects for these derivatives are discussed in this study. According to the calculation results, the side chain moiety extends the π-delocalization length from the porphyrin core to the side chain moiety. The substituted group with a stronger electron-donating ability increases the energy level of highest occupied molecular orbital (E HOMO ). The side chain moiety with a lower resonance energy decreases E HOMO , the energy level of the lowest unoccupied molecular orbital (E LUMO ), and the energy gap (E g ) between HOMO and LUMO in the porphyrin and zinc(II)–porphyrin derivatives. The natural bonding orbital (NBO) analysis determines the possible electron transfer mechanism from the electron-donating to -withdrawing groups (the side chain moiety) in these porphyrin derivatives. The projected density of state (PDOS) analysis shows that the electron-donating group affects the electron density distribution in both HOMO and LUMO, and the side chain moiety influence the electron density distribution in LUMO. The calculated photo-physical properties (absorption wavelengths and the related oscillator strength, f) in dichloromethane environment for porphyrin and zinc(II)–porphyrin derivatives have been simulated by using the TD-DFT method within the Polarizable Continuum Model (PCM). The present of both of the substituted group and the side chain moiety in these derivatives results in a red shift and broadening of the range of the absorption peaks of the Q/Soret band as compared to porphin. -- Highlights: • Side chain moiety extends the π-delocalization for the porphyrins. • Substituted group increases the energy of highest occupied molecular orbital. • Side chain moiety influences the Q/Soret band of

Phenotypic modulation of auto-reactive cells by insertion of tolerogenic molecules via MSC-derived exosomes.

Science.gov (United States)

Mokarizadeh, Aram; Delirezh, Nowruz; Morshedi, Ahhmad; Mosayebi, Ghasem; Farshid, Amir-Abbas; Dalir-Naghadeh, Bahram

2012-01-01

Auto-reactive cells-mediated immune responses are responsible for the current tissue damages during autoimmunity. Accordingly, functional modulation of auto-reactive cells has been a pivotal aim in many of recent studies. In the current study, we investigated the possibility for insertion of regulatory molecules onto auto-reactive cells through exosomal nano-shuttles as a novel approach for phenotype modification of auto-reactive cells. The exosomes were isolated from supernatant of mesenchymal stem cells culture. Resultant exosomes co-cultured with lymphocytes were harvested from established EAE mice in the presence of antigenic MOG35-55 peptide. After 24 hr, insertion of exosomal tolerogenic molecules (PD-L1, TGF-β, galectin-1) onto auto-reactive cells were explored through flow cytometry. The potency of exosomal inserted membrane molecules to modulate phenotype of auto-reactive lymphocytes was assessed upon ELISA test for their-derived cytokines IFN-γ and IL-17. Incorporation of exosomal molecules into lymohocytes' membrane was confirmed by flow cytometric analyses for surface levels of mentioned molecules. Additionally, the decreased secretion of IFN-γ and IL-17 were detected in exosome pre-treated lymphocytes upon stimulation with MOG peptide. Mesenchymal stem cells -derived exosomes showed to be efficient organelles for insertion of bioactive tolerogenic molecules onto auto-reactive cells and modulation of their phenotypes.

Synergistic Effects of PPARγ Ligands and Retinoids in Cancer Treatment

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Masahito Shimizu

2008-01-01

Full Text Available Peroxisome proliferator-activated receptors (PPARs are members of the nuclear receptor superfamily. The activation of PPARs by their specific ligands is regarded as one of the promising strategies to inhibit cancer cell growth. However, recent clinical trials targeting several common cancers showed no beneficial effect when PPAR ligands are used as a monotherapy. Retinoid X receptors (RXRs, which play a critical role in normal cell proliferation as a master regulator for nuclear receptors, preferentially form heterodimers with PPARs. A malfunction of RXRα due to phosphorylation by the Ras/MAPK signaling pathway is associated with the development of certain types of human malignancies. The activation of PPARγ/RXR heterodimer by their respective ligands synergistically inhibits cell growth, while inducing apoptosis in human colon cancer cells when the phosphorylation of RXRα was inhibited. We herein review the synergistic antitumor effects produced by the combination of the PPAR, especially PPARγ, ligands plus other agents, especially retinoids, in a variety of human cancers. We also focus on the phosphorylation of RXRα because the inhibition of RXRα phosphorylation and the restoration of its physiological function may activate PPAR/RXR heterodimer and, therefore, be a potentially effective and critical strategy for the inhibition of cancer cell growth.

A designated centre for people with disabilities operated by Ability West, Galway

LENUS (Irish Health Repository)

Orfali, Nina

2014-05-15

Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies.

40 CFR Appendix D to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

Science.gov (United States)

2010-07-01

... the following criteria, derived from Society of Automotive Engineers (SAE) standards and recommended... Substitutes] Application Substitute Decision Conditions Comments Electronics Cleaning w/CFC-113 and MCF HFC... Sector [Acceptable Subject to Narrowed Use Limits] Application Substitute Decision Comments Electronics...

A Facile Method for Detection of Substituted Salicylic Acids Using Pyrenesulfonamide-Terminated Self-Assembled Monolayers on Silicon Oxide Surfaces

Energy Technology Data Exchange (ETDEWEB)

Han, Gyeongyeop; Choi, Jaehyuck; Lee, Jungkyu; Kumar, Ashwani; Lee, Ju-Young; Kim, Hong-Seok [Kyungpook Nation al University, Daegu (Korea, Republic of)

2016-05-15

We have developed a method for sensing substituted salicylic acids on silicon oxide surfaces. The receptor molecule was successfully immobilized onto the surface by self-assembly, and, as a demonstration, micropatterns of substituted salicylic acids were generated by soft lithography techniques. We believe that this approach used herein will not only widen the understanding of the specific interactions between salicylic acids and pyrenesulfonamide derivatives, but also be applicable to practical devices such as chemo/bio analytical sensors. We have successfully demonstrated the molecular recognition between salicylic acids and pyrene derivatives in solution by fluorescence measurement. Briefly, selective recognition was achieved using intermolecular interactions, including π-π interactions and multi-hydrogen bonds, and intramolecular hydrogen bonding between the phenolic O-H group and the adjacent C=O group.

A Facile Method for Detection of Substituted Salicylic Acids Using Pyrenesulfonamide-Terminated Self-Assembled Monolayers on Silicon Oxide Surfaces

International Nuclear Information System (INIS)

Han, Gyeongyeop; Choi, Jaehyuck; Lee, Jungkyu; Kumar, Ashwani; Lee, Ju-Young; Kim, Hong-Seok

2016-01-01

We have developed a method for sensing substituted salicylic acids on silicon oxide surfaces. The receptor molecule was successfully immobilized onto the surface by self-assembly, and, as a demonstration, micropatterns of substituted salicylic acids were generated by soft lithography techniques. We believe that this approach used herein will not only widen the understanding of the specific interactions between salicylic acids and pyrenesulfonamide derivatives, but also be applicable to practical devices such as chemo/bio analytical sensors. We have successfully demonstrated the molecular recognition between salicylic acids and pyrene derivatives in solution by fluorescence measurement. Briefly, selective recognition was achieved using intermolecular interactions, including π-π interactions and multi-hydrogen bonds, and intramolecular hydrogen bonding between the phenolic O-H group and the adjacent C=O group

Molecule of the Month

Indian Academy of Sciences (India)

Cyclo bu tadiene (1) has been one of the most popular molecules for experimentalists and theoreticians. This molecule is unstable as . it is antiaromatic ( 4,n electrons in a cyclic array). Even though some highly substituted cyclobutadienes, for example, compound 2 and the Fe(CO)3 complex of cyclobutadiene (3) are ...

Local functional derivative of the total energy and the shell structure in atoms and molecules

NARCIS (Netherlands)

Pino, R.; Markvoort, Albert. J.; Santen, van R.A.; Hilbers, P.A.J.

2003-01-01

The full and local Thomas–Fermi–Dirac energy functional derivatives are evaluated at Hartree–Fock densities for several atoms and molecules. These functions are interpreted as local chemical potentials and related mainly to kinetic energy functional derivatives. They are able to reveal the shell

265 nm laser flash photolysis of some ortho-substituted anilides and related N-formylkynurenine derivatives

Energy Technology Data Exchange (ETDEWEB)

Pileni, M P; Santus, R [Museum National d' Histoire Naturelle, 75 - Paris (France); Land, E J

1978-06-01

The physical and chemical properties of the triplet state of eight ortho-substituted anilides including N-formylkynurenine(FK), the major trp UV-photooxidation product and a remarkable photodynamic agent, have been investigated using both pulse radiolysis and 265 nm laser flash photolysis techniques. The molar extinction coefficient, the inter-system-crossing quantum yield and the oscillator strength of the T/sub 1/..-->..Tsub(n) absorption band (lambdasub(max)approximately equal 450nm) have been determined. It is shown that anilides having n..pi..* triplets readily react with most solvents whereas those having ..pi..,..pi..* triplets slowly react with alcohols. In both cases, the semi-reduced species are formed. In water, the formation of the semi-reduced species most probably involves the first excited singlet state. The triplet state properties of the FK derivatives (i.e. ortho-substituted anilides having a side chain bearing charged groups such as carboxylic or amino groups) are strongly modified by the ionization state of the charged side chain. In the case of the FK derivatives possessing an uncharged amino group, quenching of the triplet state occurs via a fast reversible electron transfer reaction from the NH/sub 2/ to the triplet anilide.

Structural characterization of some substituted azolidine molecules

International Nuclear Information System (INIS)

Andreocci, M.V.; Bossa, M.; Furlani, C.; Mattogno, G.; Zanoni, R.; Consiglio Nazionale delle Ricerche, Rome; Devillanova, F.A.; Verani, G.

1981-01-01

The electronic structure of a series of organic molecules of general formula RN - (CH 2 ) 2 - X - C = Y, which are also of interest in inorganic chemistry because of their properties as ligands towards metals, have been investigated by X-ray photoelectron spectroscopy. The results suggest a general picture of atomic charge distribution within the investigated molecules, and allow an assessment of the effect of the different substituent groups X, Y, R (X = NR', O, S, CH 2 ; Y = O, S, Se; R, R' = H, alkyl) on the electronic structure of the ligands. Satisfactory correlation is found between experimental binding energies and computed CNDO/2 atomic charges, after correction for intramolecular Madelung potentials. (orig.)

Distinct populations of hepatic stellate cells in the mouse liver have different capacities for retinoid and lipid storage.

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Diana N D'Ambrosio

Full Text Available Hepatic stellate cell (HSC lipid droplets are specialized organelles for the storage of retinoid, accounting for 50-60% of all retinoid present in the body. When HSCs activate, retinyl ester levels progressively decrease and the lipid droplets are lost. The objective of this study was to determine if the HSC population in a healthy, uninjured liver demonstrates heterogeneity in its capacity for retinoid and lipid storage in lipid droplets. To this end, we utilized two methods of HSC isolation, which leverage distinct properties of these cells, including their vitamin A content and collagen expression. HSCs were isolated either from wild type (WT mice in the C57BL/6 genetic background by flotation in a Nycodenz density gradient, followed by fluorescence activated cell sorting (FACS based on vitamin A autofluorescence, or from collagen-green fluorescent protein (GFP mice by FACS based on GFP expression from a GFP transgene driven by the collagen I promoter. We show that GFP-HSCs have: (i increased expression of typical markers of HSC activation; (ii decreased retinyl ester levels, accompanied by reduced expression of the enzyme needed for hepatic retinyl ester synthesis (LRAT; (iii decreased triglyceride levels; (iv increased expression of genes associated with lipid catabolism; and (v an increase in expression of the retinoid-catabolizing cytochrome, CYP2S1.Our observations suggest that the HSC population in a healthy, uninjured liver is heterogeneous. One subset of the total HSC population, which expresses early markers of HSC activation, may be "primed" and ready for rapid response to acute liver injury.

Dose-dependent pharmacokinetics and teratogenic activity of topical retinoids

International Nuclear Information System (INIS)

Sharma, R.P.; Willhite, C.C.; Berry, D.L.; Allen, P.V.

1990-01-01

Oral retinoid treatment can be teratogenic and topical applications are used to treat acne and smooth wrinkles. A single topical trace (2.5 μg; 191 μCi/kg) or high (1.3 mg; 195 μCi/kg) dose of all-trans-[10, 11- 3 H 2 ] retinoic acid (RA) dissolved in acetone was applied to 4 cm 2 shaved dorsal hamster skin. Peak plasma radioactivity (C max ) occurred at 12 and 36 hr and mean t1/2 values for parent PA absorption were 48 min and 2.8 hr, for trace and high dose, respectively. The dermal RA C max values were only 2% of that after an equivalent oral dose, but plasma AUC after dermal treatment was 63% of the oral value. The mean t1/2 for rapid elimination was shorter for the high (57 min) than for the trace (6.9 hr) dose, but t1/2 values for slow elimination were comparable (t1/2 high = 51.2 hr; t1/2 trace = 36.8 hr). Single topical application of 10-30 mg/kg RA or 5 mg/kg etretinate (Ro 10-9359) to pregnant hamsters (day 8) caused local hyperkeratosis, but failed to induce terata. Similar application of 10-1000 μg/kg arotinoid Ro 13-6298 caused dose-dependent terata, being twice as embryolethal by parenteral as enteric dosing. Skin toxicity and attenuated maternal blood levels limit the amount of retinoids that can reach the embryo

Retinoides (RARβ y CRBP1 en carcinoma de pulmón a células no pequeñas Retinoid expression (RARβ and CRBP1 in non-small-cell lung carcinoma

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Laura V. Mauro

2008-06-01

involved in cell growth and differentiation and may antagonize cancer progression. Their effects are mediated through nuclear receptors called Retinoic Acid Receptor (RAR and regulated by molecules such as Cellular Retinol-Binding Protein 1 (CRBP1 that function in retinol storage. The aim of this work was to analyze by immunohistochemistry the expression patterns of RARβ and CRBP1, involved in retinoid-mediated signaling, in the tumoral tissue of a cohort of stage I/II NSCLC patients (n=49 who underwent a successful surgical resection. Prognostic evaluation was performed with the multivariate Cox proportional hazard model: 44.9% of tumors were positive for RARβ staining at cytoplasmic level, while 34.7% showed nuclear staining. CRBP1 staining was observed in 61.2% of the lung tumors. No relationship was found between the number of cells expressing the studied molecules and clinical pathological features, including sex, T and N (stage, histopathology and p53 expression. Univariate analysis showed a significant association between positive cytoplasmatic expression of RARβ with shorter overall survival (Log-rank test 4.17, p=0.0412. Multivariate studies indicated that RARβ expression was not influenced by other clinical pathological parameters. In conclusion, in this cohort of stage I and II NSCLC, only the expression of RARβ at cytoplasmatic level is a significant independent unfavorable prognostic factor.

The inhibition performance of long-chain alkyl-substituted benzimidazole derivatives for corrosion of mild steel in HCl

International Nuclear Information System (INIS)

Zhang, Dongqin; Tang, Yongming; Qi, Sijun; Dong, Dawei; Cang, Hui; Lu, Gang

2016-01-01

Highlights: • Inhibition performance of long-chain alkyl-substituted benzimidazole. • Benzimidazole segment donating electrons to metal surface. • Non-polar long chain enhancing inhibition by the barrier effect. • Molecular form of DBI more tightly adsorbs on the steel than its protonated form. - Abstract: The corrosion inhibition of a new benzimidazole derivative, 6-(dodecyloxy)-1H-benzo[d]imidazole (DBI), for mild steel in 1 M HCl was investigated in this paper. Computational chemistry was performed to explore the adsorption of DBI on metal surface. Inhibition performance of DBI is attributed to both the direct interaction of benzimidazole segment with iron surface and the barrier effect of the non-polar long chain against aggressive solution. Compared to the protonated form, the molecular form of DBI could more tightly interact with iron surface. These results show that the long-chain alkyl-substituted benzimidazole derivative is of great potential application as corrosion inhibitor.

Synthesis of substituted 1-metallyl derivatives of o- and m-carboranes and some their transformations

International Nuclear Information System (INIS)

Kovredov, A.I.; Shemyakin, N.F.; Zakharkin, L.I.

1985-01-01

Synthesis of 1-metallyl substituted o- and m- carbonates is carried out, and alkylation of benzene by them is investigated. Synthesis with 30-95% yield has been carried out by the reaction of lithium derivatives with metallylchloride in the ester-benzene solution. The reaction of benzene alkylation is studied in the presence of aluminium chloride and H 2 SO 4 . Reaction mechanisms are considered

Paracetamol, 3-monoalkyl- and 3,5-dialkyl-substituted derivatives. Antioxidant activity and relationship between lipid peroxidation and cytotoxicity

NARCIS (Netherlands)

Van de Straat, R; Bijloo, G.J.; Vermeulen, N P

1988-01-01

The analgesic drug paracetamol is known to cause lipid peroxidation and hepatotoxicity after overdosage. In this paper, the relationship between lipid peroxidation and toxicity in freshly isolated hepatocytes was studied using paracetamol and three 3-monoalkyl-substituted derivatives of paracetamol.

Smart DNA vectors based on cyclodextrin polymers: compaction and endosomal release.

Science.gov (United States)

Wintgens, Véronique; Leborgne, Christian; Baconnais, Sonia; Burckbuchler, Virginie; Le Cam, Eric; Scherman, Daniel; Kichler, Antoine; Amiel, Catherine

2012-02-01

Neutral β-cyclodextrin polymers (polyβCD) associated with cationic adamantyl derivatives (Ada) can be used to deliver plasmid DNA into cells. In absence of an endosomolytic agent, transfection efficiency remains low because most complexes are trapped in the endosomal compartment. We asked whether addition of an imidazole-modified Ada can increase efficiency of polyβCD/cationic Ada-based delivery system. We synthesized two adamantyl derivatives: Ada5, which has a spacer arm between the Ada moiety and a bi-cationic polar head group, and Ada6, which presents an imidazole group. Strength of association between polyβCD and Ada derivatives was evaluated by fluorimetric titration. Gel mobility shift assay, zeta potential, and dark field transmission electron microscopy experiments demonstrated the system allowed for efficient DNA compaction. In vitro transfection experiments performed on HepG2 and HEK293 cells revealed the quaternary system polyβCD/Ada5/Ada6/DNA has efficiency comparable to cationic lipid DOTAP. We successfully designed fine-tuned DNA vectors based on cyclodextrin polymers combined with two new adamantyl derivatives, leading to significant transfection associated with low toxicity.

Effect of a bulky lateral substitution by chlorine atom and methoxy group on self-assembling properties of lactic acid derivatives

International Nuclear Information System (INIS)

Stojanović, Maja; Bubnov, Alexej; Obadović, Dušanka Ž.; Hamplová, Věra; Cvetinov, Miroslav; Kašpar, Miroslav

2014-01-01

Several chiral liquid crystalline materials derived from the lactic acid have been studied with the aim to establish the effect of bulky lateral substituents on their self-assembling properties. A chlorine atom and methoxy group have been used as lateral substituents in ortho position to ether group position on phenyl ring far from the chiral centre. All the studied materials possess tilted ferroelectric smectic C* phase in a broad temperature range. In dependence on the molecular structure namely type of lateral substituent and length of the chiral chain, the cholesteric mesophase, orthogonal paraelectric smectic A* and crystal mesophases have been detected. Lateral chlorine substitution results in decrease of both the clearing point and crystallisation temperature as well as in a distinct increase of spontaneous polarization. Bulky methoxy substitution slightly suppresses the spontaneous polarisation but strongly increases the melting point that results in monotropic peculiarity of the SmC* phase. Mesomorphic, spontaneous, structural and dielectric properties of the substituted compounds were established and compared to those of the non-substituted ones in order to contribute to better understanding of the structure–property relationship for such chiral self-assembling materials. - Highlights: • Chiral liquid crystalline materials derived from the lactic acid have been studied. • Effect of bulky lateral substituents on self-assembling properties has been established. • Bulky methoxy substitution suppresses spontaneous polarisation but increases the melting point. • The compounds might have a strong potential for many advanced electro-optic applications

RETINOID RECEPTORS IN BONE AND THEIR ROLE IN BONE REMODELING

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Petra eHenning

2015-03-01

Full Text Available Vitamin A (retinol is a necessary and important constituent of the body which is provided by food intake of retinyl esters and carotenoids. Vitamin A is known best for being important for vision, but in addition to the eye, vitamin A is necessary in numerous other organs in the body, including the skeleton. Vitamin A is converted to an active compound, all-trans-retinoic acid (ATRA, which is responsible for most of its biological actions. ATRA binds to intracellular nuclear receptors called retinoic acid receptors (RAR, RAR, RAR. RARs and closely related retinoid X receptors (RXR, RXR, RXR form heterodimers which bind to DNA and function as ligand activated transcription factors. It has been known for many years that hypervitaminosis A promotes skeleton fragility by increasing osteoclast formation and decreasing cortical bone mass. Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive. The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver and processed to ATRA. ATRA’s effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented.

Theoretical study of hydrogen storage in a truncated triangular pyramid molecule consisting of pyridine and benzene rings bridged by vinylene groups

Science.gov (United States)

Ishikawa, Shigeru; Nemoto, Tetsushi; Yamabe, Tokio

2018-06-01

Hydrogen storage in a truncated triangular pyramid molecule C33H21N3, which consists of three pyridine rings and one benzene ring bridged by six vinylene groups, is studied by quantum chemical methods. The molecule is derived by substituting three benzene rings in a truncated tetrahedron hydrocarbon C36H24 with pyridine rings. The optimized molecular structure under C 3v symmetry shows no imaginary vibrational modes at the B3LYP/cc-pVTZ level of theory. The hydrogen storage process is investigated based on the MP2/cc-pVTZ method. Like the structure before substitution, the C33H21N3 molecule has a cavity that stores a hydrogen molecule with a binding energy of - 140 meV. The Langmuir isotherm shows that this cavity can store hydrogen at higher temperatures and lower pressures than usual physisorption materials. The C33H21N3 molecule has a kinetic advantage over the C36H24 molecule because the former molecule has a lower barrier (+ 560 meV) for the hydrogen molecule entering the cavity compared with the latter molecule (+ 730 meV) owing to the lack of hydrogen atoms narrowing the opening.

T-Shaped Indan-1,3-dione derivatives as promising electron donors for bulk heterojunction small molecule solar cell

Science.gov (United States)

Adhikari, Tham; Solanke, Parmeshwar; Pathak, Dinesh; Wagner, Tomas; Bureš, Filip; Reed, Tyler; Nunzi, Jean-Michel

2017-07-01

We report on the photovoltaic performance of novel T-Shaped Indan-1,3-dione derivatives as donors in a solution processed bulk heterojunction solar cells. Small molecule bulk heterojunction solar cells of these molecules with [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) were fabricated and characterized. The preliminary characterization of these devices yielded a PCE of 0.24% and 0.33% for two separate derivatives. These low power conversion efficiencies were attributed to a high surface roughness with a large number of dewetting spots. Doping with 10% Polystyrene in the Indan-1,3-dione derivatives decreases surface roughness and dewetting spots thereby improving the efficiency of the devices. Efficiency of the devices was found as 0.39% and 0.51% for two derivatives after doping with polystyrene. The charge transfer mechanism was studied with photoluminescence quenching. The morphology and packing behavior of molecules were further studied using Atomic Force Microscopy (AFM) and X-ray diffraction (XRD).

Noval 1-substituted-3,5-dimethyl-4-[(substituted phenyl diazenyl] pyrazole derivatives: Synthesis and pharmacological activity

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Sabir Hussain

2015-05-01

Full Text Available Several-1-carbothioamide-3,5-dimethyl-4-[(substituted phenyl diazenyl] pyrazoles 2a–d, 1-(pyridine-4-ylcarbonyl-3,5-dimethyl-4-[(substituted phenyl diazenyl] pyrazoles 3a–d, 1-(5-chloro-6-fluoro-1,3-benzothiazole-2-ylthiocarbamoyl-3,5-dimethyl-4-[(substituted phenyl diazenyl] pyrazoles 4a–d and 1-[(1,2,4-triazole-4-yl carbothioamide]-3,5-dimethyl-4-[(substituted phenyl diazenyl] pyrazoles 5a–d were synthesized. The structures of the newly synthesized compounds were supported by IR, 1H NMR and mass spectral data. These compounds were investigated for their, anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, antibacterial and antifungal activities. Some of the synthesized compounds showed potent anti-inflammatory activity along with minimal ulcerogenic effect and lipid peroxidation, compared to ibuprofen and flurbiprofen. Some of the tested compounds also showed moderate antimicrobial activity against tested bacterial and fungal strains.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN): could retinoids play a causative role?

Science.gov (United States)

Mawson, Anthony R; Eriator, Ike; Karre, Sridhar

2015-01-12

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are overlapping manifestations on a spectrum of acute drug-induced conditions associated with severe blistering, skin peeling, and multi-organ damage. TEN is an eruption resembling severe scalding, with ≥30% skin detachment. SJS is a mild form of TEN, characterized histologically by epidermal keratinocyte apoptosis with dermo-epidermal separation and extensive small blisters with <10% body surface skin detachment. The syndrome can be induced by numerous medications and typically occurs 1-4 weeks after the initiation of therapy. Granulysin is found in the lesions of patients with SJS/TEN and plays a significant pathogenic role in the condition, but the overall mechanisms linking medications, granulysin, and disease manifestations remain obscure. This paper reviews evidence suggesting that the different medications implicated in SJS/TEN have the common property of interacting and synergizing with endogenous retinoids (vitamin A and its congeners), in many instances causing the latter to accumulate in and damage the liver, the main storage organ for vitamin A. It is hypothesized that liver damage leads to the spillage of toxic retinoid compounds into the circulation, resulting in an endogenous form of hypervitaminosis A and cytotoxicity with widespread apoptosis, mediated by granulysin and recognized as SJS/TEN. Subject to testing, the model suggests that symptom worsening could be arrested at onset by lowering the concentration of circulating retinoids and/or granulysin via phlebotomy or plasmapheresis or by pharmacological measures to limit their expression.

Sports doping: emerging designer and therapeutic β2-agonists.

Science.gov (United States)

Fragkaki, A G; Georgakopoulos, C; Sterk, S; Nielen, M W F

2013-10-21

Beta2-adrenergic agonists, or β2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of β2-agonists is prohibited in sports by the World Anti-Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as growth promoters in cattle fattening in the European Union. This paper reviews the last seven-year (2006-2012) literature concerning the development of novel β2-agonists molecules either by modifying the molecule of known β2-agonists or by introducing moieties producing indole-, adamantyl- or phenyl urea derivatives. New emerging β2-agonists molecules for future therapeutic use are also presented, intending to emphasize their potential use for doping purposes or as growth promoters in the near future. © 2013.

Peretinoin, an Acyclic Retinoid, Inhibits Hepatitis B Virus Replication by Suppressing Sphingosine Metabolic Pathway In Vitro

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Kazuhisa Murai

2018-01-01

Full Text Available Hepatocellular carcinoma (HCC frequently develops from hepatitis C virus (HCV and hepatitis B virus (HBV infection. We previously reported that peretinoin, an acyclic retinoid, inhibits HCV replication. This study aimed to examine the influence of peretinoin on the HBV lifecycle. HBV-DNA and covalently closed circular DNA (cccDNA were evaluated by a qPCR method in HepG2.2.15 cells. Peretinoin significantly reduced the levels of intracellular HBV-DNA, nuclear cccDNA, and HBV transcript at a concentration that did not induce cytotoxicity. Conversely, other retinoids, such as 9-cis, 13-cis retinoic acid (RA, and all-trans-retinoic acid (ATRA, had no effect or rather increased HBV replication. Mechanistically, although peretinoin increased the expression of HBV-related transcription factors, as observed for other retinoids, peretinoin enhanced the binding of histone deacetylase 1 (HDAC1 to cccDNA in the nucleus and negatively regulated HBV transcription. Moreover, peretinoin significantly inhibited the expression of SPHK1, a potential inhibitor of HDAC activity, and might be involved in hepatic inflammation, fibrosis, and HCC. SPHK1 overexpression in cells cancelled the inhibition of HBV replication induced by peretinoin. This indicates that peretinoin activates HDAC1 and thereby suppresses HBV replication by inhibiting the sphingosine metabolic pathway. Therefore, peretinoin may be a novel therapeutic agent for HBV replication and chemoprevention against HCC.

Novel fluoroquinolone derivatives bearing N-thiomide linkage with 6-substituted-2-aminobenzothiazoles: Synthesis and antibacterial evaluation

Directory of Open Access Journals (Sweden)

Prabodh Chander Sharma

2017-02-01

Full Text Available A series of novel fluoroquinolone derivatives bearing N-thiomide linkage with 6-substituted-2-aminobenzothiazole substituents at the C-7 position were synthesized to obtain potent analogs active against bacterial strains. Some compounds exhibited excellent antibacterial activity against Staphylococcus auerus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa bacterial strains. Among all the synthesized compounds 6-nitro substituted benzothiazole along with norfloxacin (4b and gatifloxacin (4l showed MIC 05 μg/ml when tested against S. auerus. Moreover, compounds 4d, 4f and 4l showed superior MIC (15, 10, and 15 μg/ml respectively against B. subtilis. The results of the present study reveal that the compounds have significant antibacterial potential and are suitable candidates for further exploration.

Transient negative ions in benzene. Some N-heterocyclic and mono-substituted derivatives

International Nuclear Information System (INIS)

Nenner, Irene

1975-01-01

Electron transmission spectroscopy is used to study transient negative ions or shape resonances in various benzene derivatives. Because of the long lifetime of these ions (τ > 10 -14 S) the vibrational structure of their first two electronic states is observed superposed on the total electron cross section curves in the energy range 0-6 eV and the corresponding adiabatic electron affinities are determined. The comparison of the first electron affinity with the first ionization potential and the energy on the first excited state of each of the derivatives is used to characterize the 'donor' substituents on the benzene ring. As a complementary study, these derivatives are studied in the liquid phase using polarography (cyclic voltametry). The linear correlation established between polarographic potentials measured in dimethyl formamide and the electron affinities was used to deduce electron affinities for several molecules which are difficult to measure in the gas phase. (author) [fr

Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry.

Science.gov (United States)

Blincoe, William D; Rodriguez-Granillo, Agustina; Saurí, Josep; Pierson, Nicholas A; Joyce, Leo A; Mangion, Ian; Sheng, Huaming

2018-04-01

Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS 1 ). Significant water/alcohol loss (>30% abundance in MS 1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs. Experiments were also extended to the analysis of two intermediates in the synthesis of suvorexant (Belsomra) with additional analysis conducted with nuclear magnetic resonance (NMR), density functional theory (DFT), and ion mobility spectrometry-mass spectrometry (IMS-MS) studies. Significant water/alcohol loss was also observed for 1-substituted 1, 2, 3-triazoles but not for the isomeric 2-substituted 1, 2, 3-triazole analogs. IMS-MS, NMR, and DFT studies were conducted to show that the preferred orientation of the 2-substituted triazole rotamer was away from the electrophilic center of the reaction, whereas the 1-subtituted triazole was oriented in close proximity to the center. Abundance of NGP product was determined to be a product of three factors: (1) proton affinity of the nucleophilic group; (2) steric impact of the nucleophile; and (3) proximity of the nucleophile to carboxylic acid/ester functional groups. Graphical Abstract ᅟ.

Substitution determination of Fmoc‐substituted resins at different wavelengths

Science.gov (United States)

Kley, Markus; Bächle, Dirk; Loidl, Günther; Meier, Thomas; Samson, Daniel

2017-01-01

In solid‐phase peptide synthesis, the nominal batch size is calculated using the starting resin substitution and the mass of the starting resin. The starting resin substitution constitutes the basis for the calculation of a whole set of important process parameters, such as the number of amino acid derivative equivalents. For Fmoc‐substituted resins, substitution determination is often performed by suspending the Fmoc‐protected starting resin in 20% (v/v) piperidine in DMF to generate the dibenzofulvene–piperidine adduct that is quantified by ultraviolet–visible spectroscopy. The spectrometric measurement is performed at the maximum absorption wavelength of the dibenzofulvene–piperidine adduct, that is, at 301.0 nm. The recorded absorption value, the resin weight and the volume are entered into an equation derived from Lambert–Beer's law, together with the substance‐specific molar absorption coefficient at 301.0 nm, in order to calculate the nominal substitution. To our knowledge, molar absorption coefficients between 7100 l mol−1 cm−1 and 8100 l mol−1 cm−1 have been reported for the dibenzofulvene–piperidine adduct at 301.0 nm. Depending on the applied value, the nominal batch size may differ up to 14%. In this publication, a determination of the molar absorption coefficients at 301.0 and 289.8 nm is reported. Furthermore, proof is given that by measuring the absorption at 289.8 nm the impact of wavelength accuracy is reduced. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. PMID:28635051

Novel Substituted Heteroaromatic Piperazine and Piperidine Derivatives as Inhibitors of Human Enterovirus 71 and Coxsackievirus A16

Directory of Open Access Journals (Sweden)

Xian Zhang

2013-04-01

Full Text Available A series of substituted heteroaromatic piperazine and piperidine derivatives were found through virtual screening based on the structure of human enterovirus 71 capsid protein VP1. The preliminary biological evaluation revealed that compounds 8e and 9e have potent activity against EV71 and Coxsackievirus A16 with low cytotoxicity.

Synthesis and antiproliferative activity of novel limonene derivatives with a substituted thiourea moiety

International Nuclear Information System (INIS)

Figueiredo, Isis M.; Santos, Luciane V. dos; Costa, Willian F. da; Silva, Cleuza C. da; Sarragiotto, Maria H.; Carvalho, Joao E. de; Sacoman, Juliana L.; Kohn, Luciana K.

2006-01-01

A series of R-(+)-limonene derivatives bearing a substituted thiourea moiety (3-13) and five S-methyl analogs (14-18) were synthesized and evaluated for their in vitro antiproliferative activity against human cancer cell lines. Compounds bearing aromatic substituents (3-6) exhibit cytostatic activity in the full panel of cell lines tested, with GI 50 values in the range of 2.5 to 24 μmol L -1 . Compounds 3, 10, 12 and 16 were the most active with GI 5 )0 values in the range of 0.41 to 3.0 μmol L -1 , against different cell lines. (author)

Silica-Supported Polyphosphoric Acid in the Synthesis of 4-Substituted Tetrahydroisoquinoline Derivatives

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Iliyan Ivanov

2013-02-01

Full Text Available We report herein an application of an α-amidoalkylation reaction, as an alternative efficient synthesis of 4-aryl- and 4-methyl-1,2,3,4-tetrahydroisoquinoline derivatives. The amides required for this purpose would result from reaction of aminoacetaldehyde dimethylacetal with different substituted benzenes in polyphosphoric acid, followed by acylation of the obtained amines with different acid chlorides or sulfochlorides. We compared the cyclisation step using conventional (milieu of acetic-trifluoracetic acid = 4:1 and solid supported reagents (SiO2/PPA, as recovered, regenerated and reused without loss of its activity catalyst. We found that in comparison to conventional methods, the yields of the reaction are greater and the reaction time is shorter.

Assessment of the efficacy and safety of a combination of 2 topical retinoids (RetinSphere) in maintaining post-treatment response of acne to oral isotretinoin.

Science.gov (United States)

Truchuelo, M T; Jiménez, N; Mavura, D; Jaén, P

2015-03-01

The high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved. To avoid or minimize relapses, topical retinoids have been used for many years as maintenance treatment. However, adverse effects frequently occur. To determine the efficacy and safety of a new retinoid combination (Retinsphere technology) in maintaining post-treatment response to oral isotretinoin. Prospective, randomized, double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin. Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other, once daily, for 3 months. Standardized photographs were taken using RBX technology at baseline, 1.5 months and 3 months. The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side. Other endpoints included lesion count, investigator-reported improvement, patient-reported improvement, impact on quality-of-life, and side effects. Although the majority of patients did not reach the total target dose of oral isotretinoin, the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side. Likewise, improved lesion count and excellent tolerance were observed. This new retinoid combination (Retinsphere technology) were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Synthesis and Structural Characterization of 1- and 2-Substituted Indazoles: Ester and Carboxylic Acid Derivatives

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Isabel Bento

2006-11-01

Full Text Available A series of indazoles substituted at the N-1 and N-2 positions with ester-containing side chains -(CH2nCO2R of different lengths (n = 0-6, 9, 10 are described.Nucleophilic substitution reactions on halo esters (X(CH2nCO2R by 1H-indazole inalkaline solution lead to mixtures of N-1 and N-2 isomers, in which the N-1 isomerpredominates. Basic hydrolysis of the ester derivatives allowed the synthesis of thecorresponding indazole carboxylic acids. All compounds were fully characterised bymultinuclear NMR and IR spectroscopies, MS spectrometry and elemental analysis; theNMR spectroscopic data were used for structural assignment of the N-1 and N-2 isomers.The molecular structure of indazol-2-yl-acetic acid (5b was determined by X-raydiffraction, which shows a supramolecular architecture involving O2-H...N1intermolecular hydrogen bonds.

Substitution determination of Fmoc-substituted resins at different wavelengths.

Science.gov (United States)

Eissler, Stefan; Kley, Markus; Bächle, Dirk; Loidl, Günther; Meier, Thomas; Samson, Daniel

2017-10-01

In solid-phase peptide synthesis, the nominal batch size is calculated using the starting resin substitution and the mass of the starting resin. The starting resin substitution constitutes the basis for the calculation of a whole set of important process parameters, such as the number of amino acid derivative equivalents. For Fmoc-substituted resins, substitution determination is often performed by suspending the Fmoc-protected starting resin in 20% (v/v) piperidine in DMF to generate the dibenzofulvene-piperidine adduct that is quantified by ultraviolet-visible spectroscopy. The spectrometric measurement is performed at the maximum absorption wavelength of the dibenzofulvene-piperidine adduct, that is, at 301.0 nm. The recorded absorption value, the resin weight and the volume are entered into an equation derived from Lambert-Beer's law, together with the substance-specific molar absorption coefficient at 301.0 nm, in order to calculate the nominal substitution. To our knowledge, molar absorption coefficients between 7100 l mol -1  cm -1 and 8100 l mol -1  cm -1 have been reported for the dibenzofulvene-piperidine adduct at 301.0 nm. Depending on the applied value, the nominal batch size may differ up to 14%. In this publication, a determination of the molar absorption coefficients at 301.0 and 289.8 nm is reported. Furthermore, proof is given that by measuring the absorption at 289.8 nm the impact of wavelength accuracy is reduced. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

One molecule of ionic liquid and tert-alcohol on a polystyrene-support as catalysts for efficient nucleophilic substitution including fluorination.

Science.gov (United States)

Shinde, Sandip S; Patil, Sunil N

2014-12-07

The tert-alcohol and ionic liquid solvents in one molecule [mim-(t)OH][OMs] was immobilized on polystyrene and reported to be a highly efficient catalyst in aliphatic nucleophilic substitution using alkali metal salts. Herein, we investigated the catalytic activity of a new structurally modified polymer-supported tert-alcohol functionalized imidazolium salt catalyst in nucleophilic substitution of 2-(3-methanesulfonyloxypropyoxy)naphthalene as a model substrate with various metal nucleophiles. The tert-alcohol moiety of the ionic liquid with a hexyl chain distance from polystyrene had a better catalytic activity compared to the other resin which lacked an alkyl linker and tert-alcohol moiety. We found that the maximum [mim-(t)OH][OMs] loading had the best catalytic efficacy among the tested polystyrene-based ionic liquids (PSILs) in nucleophilic fluorination. The catalytic efficiency of the PS[him-(t)OH][OMs] as a phase transfer catalyst (PTC) was determined by carrying out various nucleophilic substitutions using the corresponding alkali metal salts from the third to sixth periodic in CH3CN or tert-BuOH media. The scope of this protocol with primary and secondary polar substrates containing many heteroatoms is also reported. This PS[him-(t)OH][OMs] catalyst not only enhances the reactivity of alkali metal salts and reduces the formation of by-products but also affords high yield with easy isolation.

The action of a dietary retinoid on gene expression and cancer induction in electron-irradiated rat skin

International Nuclear Information System (INIS)

Burns, F.J.; Chen, S.; Xu, G.; Wu, F.; Tang, M.S.

2002-01-01

Current models of radiation carcinogenesis generally assume that the DNA is damaged in a variety of ways by the radiation and that subsequent cell divisions contribute to the conversion of the damage to heritable mutations. Cancer may seem complex and intractable, but its complexity provides multiple opportunities for preventive interventions. Mitotic inhibitors are among the strongest cancer preventive agents, not only slowing the growth rate of preneoplasias but also increasing the fidelity of DNA repair processes. Ionizing radiation, including electrons, is a strong inducer of cancer in rat skin, and dietary retinoids have shown potent cancer preventive activity in the same system. A non-toxic dietary dose of retinyl acetate altered gene expression levels 24 hours after electron irradiation of rat skin. Of the 8740 genes on an Affymetrix rat expression array, the radiation significantly (5 fold or higher) altered 188, while the retinoid altered 231, including 16 radiation-altered genes that were reversely altered. While radiation strongly affected the expression of stress response, immune/inflammation and nucleic acid metabolism genes, the retinoid most strongly affected proliferation-related genes, including some significant reversals, such as, keratin 14, retinol binding protein, and calcium binding proteins. These results point to reversal of proliferation-relevant genes as a likely basis for the anti-radiogenic effects of dietary retinyl acetate. (author)

Effect of the substitution of F on the photoswitching behavior in single molecular device

Science.gov (United States)

Bian, Baoan; Zheng, Yapeng; Yuan, Peipei; Liao, Bin; Chen, Wei; An, Xiuhua; Mo, Xiaotong; Ding, Yuqiang

2017-09-01

We carry out first-principles calculations based on density functional theory and non-equilibrium Green's function to investigate the electronic transport properties of a 5-arylidenehydantoin molecule sandwiched between two Au electrodes. A reversible switching behavior between E and Z isomerization can be observed in the device through light irradiation, and their currents display different characteristic. Furthermore, it is found that the substitution of F in the molecule enlarges the switching ratio of device. The different characteristics of currents for E/Z forms and E/Z with the substitution of F are discussed by the transmission spectra and the molecular projected self-consistent Hamiltonian states. We discuss the change of Fermi level alignment due to the substitution of F, and the polarization effect under bias. We find the negative differential resistance effect in the E form with the substitution of F, which is explained by change of molecule-electrode coupling with the varied bias. The results suggest that the 5-arylidenehydantoin molecule with the substitution of F that improves the performance of device, becoming one of the methods for improving single molecular photoswitching performance in the future.

Synthesis and in vitro antibacterial activity of N-methylnitrone and nitrovinyl derivatives of some N-substituted 2-chloroindol-3-carboxaldehydes

Energy Technology Data Exchange (ETDEWEB)

Gatti, R.; Cavrini, V.; Roveri, P.; Bianucci, F.; Legnani, P.

1981-02-01

N-methylnitrones and nitrovinyl derivatives from 1-substituted-2-chloroindol-3-carboxaldehydes were synthesized and evaluated for their in vitro antibacterial activity. Some nitrovinyl derivatives displayed good in vitro activity against Gram-positive bacteria; the compound (II e), 1-(o-chlorobenzyl)-2-chloro-3-(2-nitroethenyl)indole, was more active than nitrofurantoin against Staphylococcus aureus and Streptococcus pyogenes. Some structure-activity relationships are discussed.

Product study of 1-adamantyl and 1-bicyclo[2.2.2]octyl radicals in hydrocarbon solvents. An unusually large hydrogen isotope effect

International Nuclear Information System (INIS)

Engel, P.S.; Chae, W.K.; Baughman, S.A.; Marschke, G.E.; Lewis, E.S.; Timberlake, J.W.; Luedtke, A.E.

1983-01-01

1-Adamantyl (ada.) and 1-bicyclo[2.2.2]octyl (bo.) radicals have been generated by photolysis of the corresponding azoalkanes in various hydrocarbon solvents. Both radicals abstract hydrogen readily from saturated hydrocarbons and they add to aromatic rings much faster than tert-butyl. does. Despite its reactivity, ada. is remarkably selective in hydrogen atom abstraction, preferring a benzylic hydrogen 25:1 over a cyclohexane hydrogen. The effect of solvent viscosity indicates that formation of the radical dimers biada and bibo occurs in the solvent cage. The most striking result of this work is a deuterium isotope effect of 25 for hydrogen transfer from cyclohexane to ada. at 65 0 C. Steric compression in the transition state is postulated to cause an unusually large tunnel correction and hence a large k/sub H//k/sub D/. 6 tables

Structure formation in bis(terpyridine) derivative adlayers: molecule-substrate versus molecule-molecule interactions.

Science.gov (United States)

Hoster, Harry E; Roos, Matthias; Breitruck, Achim; Meier, Christoph; Tonigold, Katrin; Waldmann, Thomas; Ziener, Ulrich; Landfester, Katharina; Behm, R Jürgen

2007-11-06

The influence of the substrate and the deposition conditions-vapor deposition versus deposition from solution-on the structures formed upon self-assembly of deposited bis(terpyridine) derivative (2,4'-BTP) monolayers on different hexagonal substrates, including highly oriented pyrolytic graphite (HOPG), Au(111), and (111)-oriented Ag thin films, was investigated by high-resolution scanning tunneling microscopy and by model calculations of the intermolecular energies and the lateral corrugation of the substrate-adsorbate interaction. Similar quasi-quadratic network structures with almost the same lattice constants obtained on all substrates are essentially identical to the optimum configuration expected from an optimization of the adlayer structure with C-H...N-type bridging bonds as a structure-determining factor, which underlines a key role of the intermolecular interactions in adlayer order. Slight distortions from the optimum values to form commensurate adlayer structures on the metal substrates and the preferential orientation of the adlayer with respect to the substrate are attributed to the substrate-adsorbate interactions, specifically, the lateral corrugation in the substrate-adsorbate interaction upon lateral displacement and rotation of the adsorbed BTP molecules. The fact that similar adlayer structures are obtained on HOPG under ultrahigh vacuum conditions (solid|gas interface) and on HOPG in trichlorobenzene (solid|liquid interface) indicates that the intermolecular interactions are not severely affected by the solvent.

Synthesis and Biological Activity of Some 3, 5-Diarylisoxazoline Derivatives: Reaction of Substituted Chalcones with Hydroxylamine Hydrochloride

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Vandana Sharma

2010-01-01

Full Text Available A series of 3-aryl-5-styrylisoxazoline/ 3,5-diarylisoxazoline derivatives were synthesized by the reaction of appropriately substituted chalcones and hydroxylamine hydrochloride in presence of alkali in ethanol. The synthesized heterocycles have been characterized on the basis of their chemical properties and spectroscopic data. These compounds were tested for biological activity against a variety of test organisms

Synthesis, Structure and Properties of Various Molecules Based on the 4,8,12-trioxa-4,8,12,12c-tetrahydrodibenzo[cd,mn]pyrene System With an Evaluation of the Effect Differing Molecular Substitution Patterns Has on the Space Group Symmetry

DEFF Research Database (Denmark)

Faldt, André; Krebs, Frederik C; Thorup, Niels

1997-01-01

of opposite chirality are present within the unit cell, Finally compound 13 crystallises in a centrosymmetric space group. The room temperature pyroelectric coefficient of 3 has been determined, The spatial extent of the trioxatriangulene ground system has been perturbed by chemical substitution......4,8,12-Trioxa-4,8,12,12c-tetrahydrodibenzo [cd,mn]pyrene (3),2,6,10-tri-tert-butyl-4,8,12 -trioxa-4,8,12,12c-tetrahydrodibenzo [cd,mn]pyrene (11) and 2,6,10-tri-tert-butyl-4,8,12-trioxa-12c -methyl-4,8,12,12c -tetrahydrodibenzo[cd,mn]pyrene (12)have been synthesised and their crystal structures...... and the effect: of the substitutions upon the space group symmetry of the chemical derivative has been uncovered by X-ray structural resolution, The non-centrosymmetric point group symmetry of the molecules is reflected in a non-centrosymmetric space group symmetry whenever the spatial perturbations do...

Liver X receptors balance lipid stores in hepatic stellate cells through Rab18, a retinoid responsive lipid droplet protein.

Science.gov (United States)

O'Mahony, Fiona; Wroblewski, Kevin; O'Byrne, Sheila M; Jiang, Hongfeng; Clerkin, Kara; Benhammou, Jihane; Blaner, William S; Beaven, Simon W

2015-08-01

Liver X receptors (LXRs) are determinants of hepatic stellate cell (HSC) activation and liver fibrosis. Freshly isolated HSCs from Lxrαβ(-/-) mice have increased lipid droplet (LD) size, but the functional consequences of this are unknown. Our aim was to determine whether LXRs link cholesterol to retinoid storage in HSCs and how this impacts activation. Primary HSCs from Lxrαβ(-/-) and wild-type mice were profiled by gene array during in vitro activation. Lipid content was quantified by high-performance liquid chromatography and mass spectroscopy. Primary HSCs were treated with nuclear receptor ligands, transfected with small interfering RNA and plasmid constructs, and analyzed by immunocytochemistry. Lxrαβ(-/-) HSCs have increased cholesterol and retinyl esters. The retinoid increase drives intrinsic retinoic acid receptor signaling, and activation occurs more rapidly in Lxrαβ(-/-) HSCs. We identify Rab18 as a novel retinoic acid-responsive, LD-associated protein that helps mediate stellate cell activation. Rab18 mRNA, protein, and membrane insertion increase during activation. Both Rab18 guanosine triphosphatase activity and isoprenylation are required for stellate cell LD loss and induction of activation markers. These phenomena are accelerated in Lxrαβ(-/-) HSCs, where there is greater retinoic acid flux. Conversely, Rab18 knockdown retards LD loss in culture and blocks activation, just like the functional mutants. Rab18 is also induced with acute liver injury in vivo. Retinoid and cholesterol metabolism are linked in stellate cells by the LD-associated protein Rab18. Retinoid overload helps explain the profibrotic phenotype of Lxrαβ(-/-) mice, and we establish a pivotal role for Rab18 GTPase activity and membrane insertion in wild-type stellate cell activation. Interference with Rab18 may have significant therapeutic benefit in ameliorating liver fibrosis. © 2015 by the American Association for the Study of Liver Diseases.

Liver X Receptors Balance Lipid Stores in Hepatic Stellate Cells via Rab18, a Retinoid Responsive Lipid Droplet Protein

Science.gov (United States)

O’Mahony, Fiona; Wroblewski, Kevin; O’Byrne, Sheila M.; Jiang, Hongfeng; Clerkin, Kara; Benhammou, Jihane; Blaner, William S.; Beaven, Simon W.

2014-01-01

Liver X receptors (LXRs) are determinants of hepatic stellate cell (HSC) activation and liver fibrosis. Freshly isolated HSCs from Lxrαβ−/− mice have increased lipid droplet (LD) size but the functional consequences of this are unknown. Our aim was to determine whether LXRs link cholesterol to retinoid storage in HSCs and how this impacts activation. Primary HSCs from Lxrαβ−/− and wild-type (WT) mice were profiled by gene array during in vitro activation. Lipid content was quantified by HPLC and mass spectroscopy. Primary HSCs were treated with nuclear receptor ligands, transfected with siRNA and plasmid constructs, and analyzed by immunocytochemistry. Lxrαβ−/− HSCs have increased cholesterol and retinyl esters (CEs & REs). The retinoid increase drives intrinsic retinoic acid receptor (RAR) signaling and activation occurs more rapidly in Lxrαβ−/− HSCs. We identify Rab18 as a novel retinoic acid responsive, lipid droplet associated protein that helps mediate stellate cell activation. Rab18 mRNA, protein, and membrane insertion increase during activation. Both Rab18 GTPase activity and isoprenylation are required for stellate cell lipid droplet loss and induction of activation markers. These phenomena are accelerated in the Lxrαβ−/− HSCs, where there is greater retinoic acid flux. Conversely, Rab18 knockdown retards lipid droplet loss in culture and blocks activation, just like the functional mutants. Rab18 is also induced with acute liver injury in vivo. Conclusion Retinoid and cholesterol metabolism are linked in stellate cells by the LD associated protein, Rab18. Retinoid overload helps explain the pro-fibrotic phenotype of Lxrαβ−/− mice and we establish a pivotal role for Rab18 GTPase activity and membrane insertion in wild-type stellate cell activation. Interference with Rab18 may have significant therapeutic benefit in ameliorating liver fibrosis. PMID:25482505

Pulse gas chromatographic study of adsorption of substituted aromatics and heterocyclic molecules on MIL-47 at zero coverage.

Science.gov (United States)

Duerinck, Tim; Couck, Sarah; Vermoortele, Frederik; De Vos, Dirk E; Baron, Gino V; Denayer, Joeri F M

2012-10-02

The low coverage adsorptive properties of the MIL-47 metal organic framework toward aromatic and heterocyclic molecules are reported in this paper. The effect of molecular functionality and size on Henry adsorption constants and adsorption enthalpies of alkyl and heteroatom functionalized benzene derivates and heterocyclic molecules was studied using pulse gas chromatography. By means of statistical analysis, experimental data was analyzed and modeled using principal component analysis and partial least-squares regression. Structure-property relationships were established, revealing and confirming several trends. Among the molecular properties governing the adsorption process, vapor pressure, mean polarizability, and dipole moment play a determining role.

Carotenoids and retinoids in Finnish foods: dairy products and eggs.

Science.gov (United States)

Ollilainen, V; Heinonen, M; Linkola, E; Varo, P; Koivistoinen, P

1989-09-01

As part of an overall composition study of Finnish foods, the carotenoid and retinoid content of 20 dairy product samples and eggs were determined by HPLC. The total beta-carotene (all-trans beta-carotene plus 15-cis beta-carotene) was quantitated for dairy products. For egg and egg yolk, lutein content was also determined. Only traces of lycopene, cryptoxanthin, and alpha-carotene were present. All-trans retinol and 13-cis retinol were the major retinoids in dairy products. Small amounts of 9-cis, 11-cis, and 9,11-cis retinols were found. High values of both retinol and beta-carotene were found in full fat cheeses and whipping cream: from 179.0 (cheese, Edam-type) to 318.7 micrograms/100 g (whipping cream) and from 86.7 (cheese, Edam-type) to 186.5 micrograms/100 g (whipping cream) for all-trans retinol and total beta-carotene, respectively. The retinol content averaged 16.3, 32.6, and 52.2 and that of beta-carotene 9.6, 16.7, and 3.0 micrograms/100 g in milk (1.9% fat), milk (3.9% fat), and human milk, respectively. The major pigment in eggs and egg yolk was lutein, 619.5 micrograms/100 g in eggs and 1575.8 micrograms/100 g in egg yolk. According to this study, at the present level of consumption in Finland, milk, milk products (excluding butter), and eggs result in a daily intake of about 350 retinol equivalents, and consequently, are a major source of vitamin A.

HPMA copolymer-based polymer conjugates for the delivery and controlled release of retinoids

Czech Academy of Sciences Publication Activity Database

Lidický, Ondřej; Šírová, Milada; Etrych, Tomáš

2016-01-01

Roč. 65, Suppl. 2 (2016), S233-S241 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 ; RVO:61388971 Keywords : polymer conjugate * retinoid * HPMA Subject RIV: EB - Genetics ; Molecular Biology; EA - Cell Biology (MBU-M) Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S233.pdf

Correlating substituent parameter values to electron transport properties of molecules

International Nuclear Information System (INIS)

Vedova-Brook, Natalie; Matsunaga, Nikita; Sohlberg, Karl

2004-01-01

There are a vast number of organic compounds that could be considered for use in molecular electronics. Because of this, the need for efficient and economical screening tools has emerged. We demonstrate that the substituent parameter values (σ), commonly found in advanced organic chemistry textbooks, correlate strongly with features of the charge migration process, establishing them as useful indicators of electronic properties. Specifically, we report that ab initio derived electronic charge transfer values for 16 different substituted aromatic molecules for molecular junctions correlate to the σ values with a correlation coefficient squared (R 2 ) of 0.863

Substitution of matrices over rings

NARCIS (Netherlands)

Hautus, M.L.J.

1995-01-01

For a given commutative ring with an identity element, we define and study the substitution of a matrix with entries in into a matrix polynomial or rational function over . A Bezout-type remainder theorem and a "partial-substitution rule" are derived and used to obtain a number of results. The

Muon substituted free radicals

International Nuclear Information System (INIS)

Burkhard, P.; Fischer, H.; Roduner, E.; Strub, W.; Gygax, F.N.; Brinkman, G.A.; Louwrier, P.W.F.; McKenna, D.; Ramos, M.; Webster, B.C.

1984-01-01

Spin polarized energetic positive muons are injected as magnetic probes into unsaturated organic liquids. They are implemented via fast chemical processes ( -10 s) in various molecules. Of particular interest among these are muonium substituted free radicals. The technique allows determination of accurate rate coefficients for fast chemical reactions of radicals. Furthermore, radiochemical processes occuring in picoseconds after injection of the muon are studied. Of fundamental interest are also the structural and dynamical implications of substituting a proton by a muon, or in other terms, a hydrogen atom by a muonium atom. Selected examples for each of these three types of experiments are given. (Auth.)

Studies on Synthesis of Some Novel Heterocyclic Azlactone Derivatives and Imidazolinone Derivatives and their Antimicrobial Activity

Directory of Open Access Journals (Sweden)

Rakesh N. Mistry

2005-01-01

Full Text Available p - Methyl benzoic acid on reaction with phosphorus pentachloride gives p - methyl benzoyl chloride derivative which on condensation with glycine gives p - methyl benzoyl glycine derivative. Now, this p - methyl benzoyl glycine derivative on condensation with various substituted aldehydes gives corresponding substituted 4 - [aryl methylidine] - 2 - [p - methyl phenyl] - oxazole - 5 - one derivatives [1(a-j]. Further, these derivatives [1(a-j] on condensation with 4 , 4’ - diamino diphenyl sulphone gives corresponding substituted imidazolinone - dibenzsulphone derivatives [2(a-j], on condensation with 4 , 4’ - diamino diphenyl methane gives corresponding substituted imidazolinone - dibenzmethane derivatives [3(a-j], on condensation with 4,4’- diamino benzanilide gives corresponding substituted imidazolinone - benzanilide derivatives [4(a-j] and on condensation with 2 - amino pyridine gives corresponding substituted imidazolinone - pyridine derivatives [5(a-j] respectively. Structure elucidation of synthesised compounds has been made on the basis of elemental analysis, I.R. spectral studies and 1H N.M.R. spectral studies. The antimicrobial activity of the synthesised compounds has been studied against the cultures “Staphylococcus aureus”, “Escherichia coli” and “Candela albicans”.

Synthesis of novel 4,6-di(substituted)amino-1,2-dihydro-1,3,5-triazine derivatives as topical antiseptic agents.

Science.gov (United States)

Maeda, Shirou; Kita, Toshiko; Meguro, Kanji

2009-02-12

A series of novel 4,6-di(substituted)amino-1,2-dihydro-1,3,5-triazine derivatives designed to have ClogP of 5.1-7.5 was synthesized and evaluated for their antiseptic properties by MIC and MBC tests against Gram-positive and Gram-negative bacteria, including MRSA, VRE, and P. aeruginosa. Among these compounds, 4-alkyl-6-aralkyl derivatives having ClogP of 6.6-7.1 and 4-alkyl-6-aryl or 4,6-dialkyl derivatives with ClogP of 6.0-6.4 showed pronounced antibacterial activities in both tests.

Cell-mediated immunity against human retinal extract, S-antigen, and interphotoreceptor retinoid binding protein in onchocercal chorioretinopathy

NARCIS (Netherlands)

van der Lelij, A.; Rothova, A.; Stilma, J. S.; Hoekzema, R.; Kijlstra, A.

1990-01-01

Autoimmune mechanisms are thought to be involved in the pathogenesis of onchocercal chorioretinopathy. Cell-mediated immune responses to human retinal S-antigen, interphotoreceptor retinoid binding protein (IRBP), and crude retinal extract were investigated in patients with onchocerciasis from

N9-Substituted N(6)-[(3-methylbut-2-en-1-yl)amino]purine derivatives and their biological activity in selected cytokinin bioassays

Czech Academy of Sciences Publication Activity Database

Mik, V.; Szüčová, Lucie; Spíchal, Lukáš; Plíhal, O.; Nisler, Jaroslav; Zahajská, L.; Doležal, Karel; Strnad, Miroslav

2011-01-01

Roč. 19, č. 23 (2011), s. 7244-7251 ISSN 0968-0896 R&D Projects: GA MŠk ED0007/01/01; GA ČR GA522/09/1576 Keywords : N6-[(3-Methylbut-2-en-1-yl)amino]purine * Isopentenyladenine derivatives * N9-Substituted derivatives * Cytokinins * Cytokinin receptors Subject RIV: EF - Botanics Impact factor: 2.921, year: 2011

2D QSAR studies of the inhibitory activity of a series of substituted purine derivatives against c-Src tyrosine kinase

OpenAIRE

Mukesh C. Sharma

2016-01-01

A series of 34 substituted purine analogues derivatives were subjected to quantitative structure-activity relationship analyses as inhibitors of c-Src tyrosine kinase. Partial least squares regression was applied to derive QSAR models, which were further validated for statistical significance by internal and external validation. The best QSAR model developed had a good predictive correlation coefficient (r2) of 0.8319, a significant cross-validated correlation coefficient (q2) of 0.7550, and ...

Retinoid Expression in Onchocercal Skin Disease: Pilot Study.

Science.gov (United States)

Mawson, Anthony R; Makunde, Williams H; Penman, Alan D; Hernandez Morales, Veronica de Los Angeles; Kalinga, Akili K; Francis, Filbert; Rubinchik, Semyon; Kibweja, Addow

2017-01-01

Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA ( r 2  = 0.25, P  = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of

Duration of oral tetracycline-class antibiotic therapy and use of topical retinoids for the treatment of acne among general practitioners (GP): A retrospective cohort study.

Science.gov (United States)

Barbieri, John S; Hoffstad, Ole; Margolis, David J

2016-12-01

Guidelines recommend limiting the duration of oral antibiotic therapy in acne to 3 to 6 months and prescribing concomitant topical retinoids for all patients. We sought to evaluate the duration of therapy with oral tetracyclines and the use of topical retinoids among patients with acne treated primarily by general practitioners in the United Kingdom. We conducted a retrospective cohort study using the Health Improvement Network database. The mean duration of therapy was 175.1 days. Of antibiotic courses, 62% were not associated with a topical retinoid; 29% exceeded 6 months in duration. If all regions were to achieve uses similar to the region with the shortest mean duration of therapy, approximately 3.3 million antibiotic days per year could be avoided in the United Kingdom. The Health Improvement Network does not include information on acne severity and clinical outcomes. Prescribing behavior for oral antibiotics in the treatment of acne among general practitioners is not aligned with current guideline recommendations. Increasing the use of topical retinoids and considering alternative agents to oral antibiotics when appropriate represent opportunities to reduce antibiotic exposure and associated complications such as antibiotic resistance and to improve outcomes in patients treated for acne. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Towards single-molecule detection of intramolecular exciplexes: Photophysics of a benzanthrone derivative

Energy Technology Data Exchange (ETDEWEB)

Hattori, Akifumi [Graduate School of Bio-Applications and Systems Engineering (BASE), Tokyo University of Agriculture and Technology, 2-24-16 Naka-machi, Koganei, Tokyo, 184-8588 (Japan); Department of Organic and Polymeric Materials, Tokyo Institute of Technology, Ookayama 2-12-1-S8, Meguro-ku, Tokyo, 152-8552 (Japan); Sato, Hisaya [Graduate School of Bio-Applications and Systems Engineering (BASE), Tokyo University of Agriculture and Technology, 2-24-16 Naka-machi, Koganei, Tokyo, 184-8588 (Japan); Vacha, Martin [Department of Organic and Polymeric Materials, Tokyo Institute of Technology, Ookayama 2-12-1-S8, Meguro-ku, Tokyo, 152-8552 (Japan)]. E-mail: vacha@op.titech.ac.jp

2007-01-15

We report luminescence study of intramolecular exciplexes based on an aminobenzanthrone derivative, dimethyl-amino-N-acetyl-3-aminobenzanthrone (BDA). The BDA compound shows strong dependence of the exciplex emission band intensity on the solvent dielectric function and moderate dependence on its viscosity. The exciplex emission mechanism is discussed in view of the unusual solvent polarity dependence and solvent-dependent excited state lifetimes. Preliminary results on single-molecule detection in polymer films are also presented.

Towards single-molecule detection of intramolecular exciplexes: Photophysics of a benzanthrone derivative

International Nuclear Information System (INIS)

Hattori, Akifumi; Sato, Hisaya; Vacha, Martin

2007-01-01

We report luminescence study of intramolecular exciplexes based on an aminobenzanthrone derivative, dimethyl-amino-N-acetyl-3-aminobenzanthrone (BDA). The BDA compound shows strong dependence of the exciplex emission band intensity on the solvent dielectric function and moderate dependence on its viscosity. The exciplex emission mechanism is discussed in view of the unusual solvent polarity dependence and solvent-dependent excited state lifetimes. Preliminary results on single-molecule detection in polymer films are also presented

Ion-Molecule Reaction Dynamics.

Science.gov (United States)

Meyer, Jennifer; Wester, Roland

2017-05-05

We review the recent advances in the investigation of the dynamics of ion-molecule reactions. During the past decade, the combination of single-collision experiments in crossed ion and neutral beams with the velocity map ion imaging detection technique has enabled a wealth of studies on ion-molecule reactions. These methods, in combination with chemical dynamics simulations, have uncovered new and unexpected reaction mechanisms, such as the roundabout mechanism and the subtle influence of the leaving group in anion-molecule nucleophilic substitution reactions. For this important class of reactions, as well as for many fundamental cation-molecule reactions, the information obtained with crossed-beam imaging is discussed. The first steps toward understanding micro-solvation of ion-molecule reaction dynamics are presented. We conclude with the presentation of several interesting directions for future research.

On the trends of Fukui potential and hardness potential derivatives in isolated atoms vs. atoms in molecules.

Science.gov (United States)

Bhattacharjee, Rituparna; Roy, Ram Kinkar

2014-10-28

In the present study, trends of electronic contribution to molecular electrostatic potential [Vel(r¯)(r=0)], Fukui potential [v(+)f|(r=0) and v(-)f|(r=0)] and hardness potential derivatives [Δ(+)h(k) and Δ(-)h(k)] for isolated atoms as well as atoms in molecules are investigated. The generated numerical values of these three reactivity descriptors in these two electronically different situations are critically analyzed through the relevant formalism. Values of Vel(r¯) (when r → 0, i.e., on the nucleus) are higher for atoms in molecules than that of isolated atoms. In contrast, higher values of v(+)|(r=0) and v(-)|(r=0) are observed for isolated atoms compared to the values for atoms in a molecule. However, no such regular trend is observed for the Δ(+)h(k) and Δ(-)h(k) values, which is attributed to the uncertainty in the Fukui function values of atoms in molecules. The sum of Fukui potential and the sum of hardness potential derivatives in molecules are also critically analyzed, which shows the efficacy of orbital relaxation effects in quantifying the values of these parameters. The chemical consequence of the observed trends of these descriptors in interpreting electron delocalization, electronic relaxation and non-negativity of atomic Fukui function indices is also touched upon. Several commonly used molecules containing carbon as well as heteroatoms are chosen to make the investigation more insightful.

Ultrastructure and 3H-TdR autoradiography after topical application of aromatic retinoid in guinea pigs

International Nuclear Information System (INIS)

Ueda, Keiichi; Maruo, Mitsuru; Inoue, Yuji; Wakabayashi, Shunji

1981-01-01

Histological, autoradiographical and electron microscopical investigations were performed on the epidermis of guinea pigs after topical application of 0.1% aromatic retinoid ointment for 7 days. Histologically, the epidermis exhibited a thickening of granular layer and acanthosis, without a prolonged rete ridge. Labelling indices were 3 to 4 times higher than in the control epidermis. Electron microscopically, the nuclei in the spinous and the basal layer were large in size and nucleoli were increased in number. In the cytoplasm, tonofilaments were reduced in number and lots of vacuoles containing less dense amorphous material appeared. Amorphous material was present in the intercellular spaces of the epidermis. Differentiation and proliferation of the epidermis in guinea pigs after topical application of aromatic retinoid showed almost the same response in quantity to the epidermis after topical application of retinoic acid, while the epidermal alternation was slight in degree than in the epidermis after topical application of retinoic acid. (author)

Synthesis of 2-azetidinones substituted quinoline derivative

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Mashelkar Uday C.

2013-01-01

Full Text Available Acetanilide is converted into 2-chloro-3-formyl quinoline by reacting with DMF-POCl3 at 80-90ºC and then condensed with aromatic primary amines to give Schiff bases (3a-3c. These Schiff bases are then reacted with acid chlorides in the presence of base in toluene to give 1, 3, 4-substituted 2-azetidinones.

Dynamics, Miscibility, and Morphology in Polymer-Molecule Blends: The Impact of Chemical Functionality

KAUST Repository

Do, Khanh

2015-10-22

In the quest to improve the performance of organic bulk-heterojunction solar cells, many recent efforts have focused on developing molecular and polymer alternatives to commonly used fullerene acceptors. Here, molecular dynamics simulations are used to investigate polymer-molecule blends comprised of the polymer donor poly(3-hexylthiophene) (P3HT) with a series of acceptors based on trialkylsilylethynyl-substituted pentacene. A matrix of nine pentacene derivatives, consisting of systematic chemical variation both in the nature of the alkyl groups and electron-withdrawing moieties appended to the acene, is used to draw connections between the chemical structure of the acene acceptor and the nanoscale properties of the polymer-molecule blend. These connections include polymer and molecular diffusivity, donor-acceptor packing and interfacial (contact) area, and miscibility. The results point to the very significant role that seemingly modest changes in chemical structure play during the formation of polymer-molecule blend morphologies.

Dynamics, Miscibility, and Morphology in Polymer-Molecule Blends: The Impact of Chemical Functionality

KAUST Repository

Do, Khanh; Risko, Chad; Anthony, John E; Amassian, Aram; Bredas, Jean-Luc

2015-01-01

In the quest to improve the performance of organic bulk-heterojunction solar cells, many recent efforts have focused on developing molecular and polymer alternatives to commonly used fullerene acceptors. Here, molecular dynamics simulations are used to investigate polymer-molecule blends comprised of the polymer donor poly(3-hexylthiophene) (P3HT) with a series of acceptors based on trialkylsilylethynyl-substituted pentacene. A matrix of nine pentacene derivatives, consisting of systematic chemical variation both in the nature of the alkyl groups and electron-withdrawing moieties appended to the acene, is used to draw connections between the chemical structure of the acene acceptor and the nanoscale properties of the polymer-molecule blend. These connections include polymer and molecular diffusivity, donor-acceptor packing and interfacial (contact) area, and miscibility. The results point to the very significant role that seemingly modest changes in chemical structure play during the formation of polymer-molecule blend morphologies.

Emitting materials based on phenylanthracene-substituted naphthalene derivatives for organic light-emitting diodes

Energy Technology Data Exchange (ETDEWEB)

Lee, Hyun Woo; Kim, Hye Jeong; Kim, Young Seok; Kim, Jwajin [Department of Chemistry, Sungkyunkwan University, Suwon 440‐746 (Korea, Republic of); Lee, Song Eun; Lee, Ho Won [Department of Information Display, Hongik University, Seoul 121-791 (Korea, Republic of); Kim, Young Kwan, E-mail: kimyk@wow.hongik.ac.kr [Department of Information Display, Hongik University, Seoul 121-791 (Korea, Republic of); Yoon, Seung Soo, E-mail: ssyoon@skku.edu [Department of Chemistry, Sungkyunkwan University, Suwon 440‐746 (Korea, Republic of)

2015-09-15

This study reports the emitting materials based on phenylanthracene-substituted naphthalene derivatives to achieve efficient electroluminescent properties for OLED applications. An OLED device using 4,4′-bis(10-phenylanthracen-9-yl)-1,1′-binaphthalene exhibited the blue emission with the CIE coordinates of (0.19, 0.16) and efficient electroluminescent properties with the luminance, power and external quantum efficiency of 1.70 cd/A, 0.79 lm/W and 1.26% at 20 mA/cm{sup 2}, respectively. Also, the other device using 1,4-bis(10-phenylanthracene-9-yl)naphthalene exhibited white emission with the CIE coordinates of (0.34, 0.43) at 7V, respectively. This device exhibits the luminance, power and external quantum efficiency of 2.22 cd/A, 1.13 lm/W and 0.86% at 20 mA/cm{sup 2}, respectively. - Highlights: • We synthesized fluorescent materials based on phenylanthracene derivatives. • Electroluminescence properties of these materials depend on the molecular structures. • These blue and white materials have great potential for application in OLEDs.

Emitting materials based on phenylanthracene-substituted naphthalene derivatives for organic light-emitting diodes

International Nuclear Information System (INIS)

Lee, Hyun Woo; Kim, Hye Jeong; Kim, Young Seok; Kim, Jwajin; Lee, Song Eun; Lee, Ho Won; Kim, Young Kwan; Yoon, Seung Soo

2015-01-01

This study reports the emitting materials based on phenylanthracene-substituted naphthalene derivatives to achieve efficient electroluminescent properties for OLED applications. An OLED device using 4,4′-bis(10-phenylanthracen-9-yl)-1,1′-binaphthalene exhibited the blue emission with the CIE coordinates of (0.19, 0.16) and efficient electroluminescent properties with the luminance, power and external quantum efficiency of 1.70 cd/A, 0.79 lm/W and 1.26% at 20 mA/cm 2 , respectively. Also, the other device using 1,4-bis(10-phenylanthracene-9-yl)naphthalene exhibited white emission with the CIE coordinates of (0.34, 0.43) at 7V, respectively. This device exhibits the luminance, power and external quantum efficiency of 2.22 cd/A, 1.13 lm/W and 0.86% at 20 mA/cm 2 , respectively. - Highlights: • We synthesized fluorescent materials based on phenylanthracene derivatives. • Electroluminescence properties of these materials depend on the molecular structures. • These blue and white materials have great potential for application in OLEDs

Allergen-Induced Dermatitis Causes Alterations in Cutaneous Retinoid-Mediated Signaling in Mice

Science.gov (United States)

Gericke, Janine; Ittensohn, Jan; Mihály, Johanna; Dubrac, Sandrine; Rühl, Ralph

2013-01-01

Nuclear receptor-mediated signaling via RARs and PPARδ is involved in the regulation of skin homeostasis. Moreover, activation of both RAR and PPARδ was shown to alter skin inflammation. Endogenous all-trans retinoic acid (ATRA) can activate both receptors depending on specific transport proteins: Fabp5 initiates PPARδ signaling whereas Crabp2 promotes RAR signaling. Repetitive topical applications of ovalbumin (OVA) in combination with intraperitoneal injections of OVA or only intraperitoneal OVA applications were used to induce allergic dermatitis. In our mouse model, expression of IL-4, and Hbegf increased whereas expression of involucrin, Abca12 and Spink5 decreased in inflamed skin, demonstrating altered immune response and epidermal barrier homeostasis. Comprehensive gene expression analysis showed alterations of the cutaneous retinoid metabolism and retinoid-mediated signaling in allergic skin immune response. Notably, ATRA synthesis was increased as indicated by the elevated expression of retinaldehyde dehydrogenases and increased levels of ATRA. Consequently, the expression pattern of genes downstream to RAR was altered. Furthermore, the increased ratio of Fabp5 vs. Crabp2 may indicate an up-regulation of the PPARδ pathway in allergen-induced dermatitis in addition to the altered RAR signaling. Thus, our findings suggest that ATRA levels, RAR-mediated signaling and signaling involved in PPARδ pathways are mainly increased in allergen-induced dermatitis and may contribute to the development and/or maintenance of allergic skin diseases. PMID:23977003

Operator substitution

NARCIS (Netherlands)

Hautus, M.L.J.

1994-01-01

Substitution of an operator into an operator-valued map is defined and studied. A Bezout-type remainder theorem is used to derive a number of results. The tensor map is used to formulate solvability conditions for linear matrix equations. Some applications to system theory are given, in particular

Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters retinoid homeostasis in maternal and perinatal tissues of the Holtzman rat

International Nuclear Information System (INIS)

Kransler, Kevin M.; Tonucci, David A.; McGarrigle, Barbara P.; Napoli, Joseph L.; Olson, James R.

2007-01-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most widely studied environmental contaminants, causes a variety of adverse health effects including teratogenesis and altered development which may be related to disruptions in retinoid homeostasis. The purpose of this study was to determine the effect that gestational administration of TCDD has on retinoid homeostasis in both pregnant Holtzman rats and developing fetuses and neonates. A single oral dose of TCDD (0, 1.5, 3, or 6 μg/kg) was administered to pregnant rats on gestation day 10, with fetuses analyzed on gestation days 17 and 20, and neonates analyzed on post natal day 7. Exposure to TCDD generally produced decreases in the concentrations of retinyl esters, such as retinyl palmitate, and retinol in maternal and perinatal liver and lung, while increasing levels in the maternal kidney. Additionally, perinatal hepatic retinol binding protein 1-dependent retinyl ester hydrolysis was also decrease by TCDD. Sensitivity of the developing perinates to TCDD appeared to have an age-related component demonstrated by an increased rate of mortality and significant alterations to body weight and length on post natal day 7 relative to that observed at gestation day 20. A unique observation made in this study was a significant decrease in lung weight observed in the perinates exposed to TCDD. Taken together, these data demonstrate that TCDD significantly alters retinoid homeostasis in tissues of the developing fetus and neonate, suggesting that their unique sensitivity to TCDD may at least be in part the result of altered retinoid homeostasis

Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

Science.gov (United States)

van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

2014-04-01

The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

Substituted Pyrazinecarboxamides: Synthesis and Biological Evaluation

Directory of Open Access Journals (Sweden)

Katarina Kralova

2006-03-01

Full Text Available Condensation of the corresponding chlorides of some substituted pyrazine-2-carboxylic acids (pyrazine-2-carboxylic acid, 6-chloropyrazine-2-carboxylic acid, 5-tert-butylpyrazine-2-carboxylic acid or 5-tert-butyl-6-chloropyrazine-2-carboxylic acid withvarious ring-substituted aminothiazoles or anilines yielded a series of amides. Thesyntheses, analytical and spectroscopic data of thirty newly prepared compounds arepresented. Structure-activity relationships between the chemical structures and the anti-mycobacterial, antifungal and photosynthesis-inhibiting activity of the evaluatedcompounds are discussed. 3,5-Bromo-4-hydroxyphenyl derivatives of substitutedpyrazinecarboxylic acid, 16-18, have shown the highest activity against Mycobacteriumtuberculosis H37Rv (54-72% inhibition. The highest antifungal effect againstTrichophyton mentagrophytes, the most susceptible fungal strain tested, was found for5-tert-butyl-6-chloro-N-(4-methyl-1,3-thiazol-2-ylpyrazine-2-carboxamide (8, MIC =31.25 μmol·mL-1. The most active inhibitors of oxygen evolution rate in spinachMolecules 2006, 11 243 chloroplasts were the compounds 5-tert-butyl-6-chloro-N-(5-bromo-2-hydroxyphenyl- pyrazine-2-carboxamide (27, IC50 = 41.9 μmol·L-1 and 5-tert-butyl-6-chloro-N-(1,3- thiazol-2-yl-pyrazine-2-carboxamide (4, IC50 = 49.5 μmol·L-1.

Small Molecule-BIO Accelerates and Enhances Marrow-Derived Mesenchymal Stem Cell in Vitro Chondrogenesis

Directory of Open Access Journals (Sweden)

Mohamadreza Baghaban Eslaminejad

2014-03-01

Full Text Available Background: Hyaline cartilage defects exhibit a major challenge in the field of orthopedic surgery owing to its limited repair capacity. On the other hand, mesenchymal stem cells (MSCs are regarded as potent cells with a property of cartilage regeneration. We aimed to optimize marrow-derived MSC chondrogenic culture using a small bioactive molecule referred to as BIO. Methods: MSCs from the marrow of NMRI mice were extracted, culture-expanded, and characterized. Micro-mass culture was then established for chondrogenic differentiation (control group. The cultures of MSC in chondrogenic medium supplemented with 0.01, 0.05, 0.1, and 1 µM BIO were taken as the experimental groups. Cartilage differentiation was examined by both histological sections and real-time PCR for Sox9, aggrecan, and collagen II at different time points. Moreover, the involvement of the Wnt pathway was investigated. Results: Based on histological sections, there was seemingly more intense metachromatic matrix produced in the cultures with 0.01 µM BIO. In this experimental group, cartilage-specific genes tended to be upregulated at day 14 compared to day 21 of the control group, indicating the accelerating effect of BIO on cartilage differentiation. Overall, there was statistically a significant increase (P=0.01 in the expression level of cartilage-specific genes in cultures with 0.01 µM BIO (enhancing effects. These upregulations appeared to be mediated through the Wnt pathway evident from the significant upregulation of T-cell factor and beta-catenin molecules (P=0.01. Conclusion: Taken together, BIO at 0.01 µM could accelerate and enhance in vitro chondrogenesis of mouse marrow-derived MSCs. Please cite this article as: Baghaban Eslaminejad MR, Fallah N. Small Molecule-BIO Accelerates and Enhances Marrow-Derived Mesenchymal Stem Cell in Vitro Chondrogenesis. Iran J Med Sci. 2014;39(2:107-116.

Exploring Covalent Allosteric Inhibition of Antigen 85C from Mycobacterium tuberculosis by Ebselen Derivatives.

Science.gov (United States)

Goins, Christopher M; Dajnowicz, Steven; Thanna, Sandeep; Sucheck, Steven J; Parks, Jerry M; Ronning, Donald R

2017-05-12

Previous studies identified ebselen as a potent in vitro and in vivo inhibitor of the Mycobacterium tuberculosis (Mtb) antigen 85 (Ag85) complex, comprising three homologous enzymes required for the biosynthesis of the mycobacterial cell wall. In this study, the Mtb Ag85C enzyme was cocrystallized with azido and adamantyl ebselen derivatives, resulting in two crystallographic structures of 2.01 and 1.30 Å resolution, respectively. Both structures displayed the anticipated covalent modification of the solvent accessible, noncatalytic Cys209 residue forming a selenenylsulfide bond. Continuous difference density for both thiol modifiers allowed for the assessment of interactions that influence ebselen binding and inhibitor orientation that were unobserved in previous Ag85C ebselen structures. The k inact /K I values for ebselen, adamantyl ebselen, and azido ebselen support the importance of observed constructive chemical interactions with Arg239 for increased in vitro efficacy toward Ag85C. To better understand the in vitro kinetic properties of these ebselen derivatives, the energetics of specific protein-inhibitor interactions and relative reaction free energies were calculated for ebselen and both derivatives using density functional theory. These studies further support the different in vitro properties of ebselen and two select ebselen derivatives from our previously published ebselen library with respect to kinetics and protein-inhibitor interactions. In both structures, the α9 helix was displaced farther from the enzyme active site than the previous Ag85C ebselen structure, resulting in the restructuring of a connecting loop and imparting a conformational change to residues believed to play a role in substrate binding specific to Ag85C. These notable structural changes directly affect protein stability, reducing the overall melting temperature by up to 14.5 °C, resulting in the unfolding of protein at physiological temperatures. Additionally, this structural

Determination of Structural Requirements of N-Substituted Tetrahydro-β-Carboline Imidazolium Salt Derivatives Using in Silico Approaches for Designing MEK-1 Inhibitors

Directory of Open Access Journals (Sweden)

Jingwei Liang

2017-06-01

Full Text Available Novel N-substituted tetrahydro-β-carboline imidazolium salt derivatives proved to have potent antitumor activity in past research. The Topomer CoMFA and CoMSIA function in Sybyl-X 2.0 software was applied for the identification of important features of N-substituted tetrahydro-β-carboline-imidazolium salt derivative moieties. In the case of Topomer CoMFA, all the compounds were split into two fragments which were used to generate a 3D invariant representation, the statistical results of the Topomer CoMFA model: q2 value of 0.700; r2 value of 0.954; with 5 optimum components. The database alignment was utilized for building the CoMSIA model, and the CoMSIA model had q2 and r2 values of 0.615 and 0.897, with 4 optimum components. Target fishing of the PharmMapper platform was utilised for finding potential targets, the human mitogen-activated protein kinase 1 (MEK-1 was found to be the primary potential target for the three compounds with the fit scores of 6.288, 5.741, and 6.721. The molecular docking technique of MOE 2015 was carried out to identify the interactions of amino acids surrounding the ligand, and correlating QASR contour maps were used to identify structural requirements of N-substituted tetrahydro-β-carboline imidazolium salt moieties. Molecular dynamics and simulation studies proved that the target protein was stable for 0.8–5 ns. The pivotal moieties of N-substituted tetrahydro-β-carboline imidazolium salt derivatives and its potential targets were verified by the QASR study, PharmMapper, and the molecular docking study which would be helpful to design novel MEK-1 inhibitors for anticancer drugs.

Theoretical studies of one- and two-photon absorption properties for three molecules with different centers (B and N) and peripheral substituted groups [N(CH{sub 3}){sub 2} and CN

Energy Technology Data Exchange (ETDEWEB)

Han Deming [State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023 (China); Feng Jikang, E-mail: jikangf@yahoo.co [State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023 (China); College of Chemistry, Jilin University, Changchun 130023 (China); Ren Aimin [State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023 (China); Shang Xiaohong [College of Chemistry, Jilin University, Changchun 130023 (China); Liu Xiaojuan [State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)

2009-08-15

Three molecules with different centers (boron and nitrogen) and peripheral substituted groups [N(CH{sub 3}){sub 2} and CN] have been theoretically studied with B3LYP/6-31G(d) associated with ZINDO and sum-over-states methods. The maximum two-photon absorption cross-section delta{sub max} of the molecule with boron (B) center and N(CH{sub 3}){sub 2} peripheral group is larger than that of the molecule with nitrogen (N) center and N(CH{sub 3}){sub 2} peripheral group. As for the two molecules with N center, the delta{sub max} is obviously increased with the change from N(CH{sub 3}){sub 2} to CN group. This indicates that the large intramolecular charge transfer is in favor of the TPA response.

Basicity comparison for di-substituted 4-nitropyridine derivatives in polar non-aqueous media

International Nuclear Information System (INIS)

Gurzynski, Lukasz; Puszko, Aniela; Chmurzynski, Lech

2007-01-01

Acid dissociation, as well as cationic homoconjugation equilibria have been studied potentiometrically in systems involving four di-substituted 4-nitropyridines and conjugate cationic acids in the polar non-aqueous solvents - aprotic protophobic acetonitrile (AN) and propylene carbonate (PC), the amphiprotic methanol (MeOH), and in the aprotic protophilic dimethyl sulfoxide (DMSO). The influence of solvent effect on the obtained acidity constants has been discussed. The acidity constants (expressed as pK a values) were compared with those previously determined in another polar protophobic aprotic solvent - acetone (AC), and obtained for the unsubstituted pyridine (Py). A comparison of the acid dissociation constants determined in all media studied has proved that the strength of the cationic acids increases on going from acetonitrile through propylene carbonate, acetone, and methanol to dimethyl sulfoxide. Furthermore, the values of acidity constants in the non-aqueous media have shown that in all the solvents studied they change according to the substituent effects. It has been also found that substituted 4-nitropyridine derivatives studied exhibit no tendency towards cationic homoconjugation in acetonitrile, propylene carbonate, and methanol and dimethyl sulfoxide. Moreover, it has been demonstrated that the acid dissociation constants determined by potentiometric titration method in all the solutions investigated correlate well with the calculated energy parameters of the protonation reactions in the gaseous phase

Basicity comparison for di-substituted 4-nitropyridine derivatives in polar non-aqueous media

Energy Technology Data Exchange (ETDEWEB)

Gurzynski, Lukasz [Department of General and Inorganic Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdansk (Poland); Puszko, Aniela [Department of Organic Chemistry, School of Economics, Wroclaw (Poland); Chmurzynski, Lech [Department of General and Inorganic Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdansk (Poland)], E-mail: lech@chemik.chem.univ.gda.pl

2007-12-15

Acid dissociation, as well as cationic homoconjugation equilibria have been studied potentiometrically in systems involving four di-substituted 4-nitropyridines and conjugate cationic acids in the polar non-aqueous solvents - aprotic protophobic acetonitrile (AN) and propylene carbonate (PC), the amphiprotic methanol (MeOH), and in the aprotic protophilic dimethyl sulfoxide (DMSO). The influence of solvent effect on the obtained acidity constants has been discussed. The acidity constants (expressed as pK{sub a} values) were compared with those previously determined in another polar protophobic aprotic solvent - acetone (AC), and obtained for the unsubstituted pyridine (Py). A comparison of the acid dissociation constants determined in all media studied has proved that the strength of the cationic acids increases on going from acetonitrile through propylene carbonate, acetone, and methanol to dimethyl sulfoxide. Furthermore, the values of acidity constants in the non-aqueous media have shown that in all the solvents studied they change according to the substituent effects. It has been also found that substituted 4-nitropyridine derivatives studied exhibit no tendency towards cationic homoconjugation in acetonitrile, propylene carbonate, and methanol and dimethyl sulfoxide. Moreover, it has been demonstrated that the acid dissociation constants determined by potentiometric titration method in all the solutions investigated correlate well with the calculated energy parameters of the protonation reactions in the gaseous phase.

Increasing human Th17 differentiation through activation of orphan nuclear receptor retinoid acid-related orphan receptor γ (RORγ) by a class of aryl amide compounds.

Science.gov (United States)

Zhang, Wei; Zhang, Jing; Fang, Leiping; Zhou, Ling; Wang, Shuai; Xiang, Zhijun; Li, Yuan; Wisely, Bruce; Zhang, Guifeng; An, Gang; Wang, Yonghui; Leung, Stewart; Zhong, Zhong

2012-10-01

In a screen for small-molecule inhibitors of retinoid acid-related orphan receptor γ (RORγ), we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the interleukin 17 (IL-17) reporter in Jurkat cells. Three of these compounds were selected for further analysis and found to activate the IL-17 reporter with potencies of ∼0.1 μM measured by EC₅₀. These compounds were shown to directly bind to RORγ by circular dichroism-based thermal stability experiments. Furthermore, they can enhance an in vitro Th17 differentiation process in human primary T cells. As RORγ remains an orphan nuclear receptor, discovery of these aryl amide compounds as functional agonists will now provide pharmacological tools for us to dissect functions of RORγ and facilitate drug discovery efforts for immune-modulating therapies.

Diffusion of anthracene derivatives on Cu(111) studied by STM and DFT

Science.gov (United States)

Wyrick, Jonathan; Bartels, Ludwig; Einstein, Theodore

2014-03-01

Substituted anthracenes have drawn attention due to their ability to diffuse uniaxially on a Cu(111) surface. We compare anthracene to three of its derivatives whose 9,10 hydrogens are replaced by elements of the chalcogen group that act as linkers binding the molecules to a Cu(111) substrate. DFT calculations shed light on STM imaging and diffusion studies on the three substituted species. We present an analysis of the DFT results in which energetic contributions to the diffusion barriers are partitioned among the Kohn-Sham orbitals, allowing us to make assignments as to how each orbital affects diffusion for each species and draw comparisons between them. Present address: Center for Nanoscale Science and Technology, NIST, Gaithersburg, MD.

The retinoids. A review of their clinical pharmacology and therapeutic use.

Science.gov (United States)

Orfanos, C E; Ehlert, R; Gollnick, H

1987-10-01

With the introduction of the synthetic retinoids, oral therapy with an acceptable risk/benefit ratio became possible for a variety of skin diseases including severe acne, psoriasis and numerous genodermatoses. This article reviews the clinical pharmacology, mechanisms of action and therapeutic use of the retinoids, particularly isotretinoin (13-cis-retinoic acid) and etretinate. The free aromatic acid of etretinate, etretin, and the new polyaromatic retinoid compounds (arotinoids) are also discussed. Isotretinoin is used clinically for oral therapy of severe acne, but is also recommended for severe Gram-negative folliculitis and rosacea not responding to traditional therapy. The results of several studies have established that acne therapy should be started with 1.0 mg/kg/day for 2 to 3 months after which the daily dosage should be lowered to 0.2 to 0.5 mg/kg/day for another 2 to 3 months. This therapeutic regimen of isotretinoin has proven to be the most successful in preventing relapses. Etretinate is particularly useful for oral therapy of widespread plaque-like, pustular and erythrodermic psoriasis, and of generalised lichen planus, Darier's disease and severe congenital ichthyoses. Whereas pustular forms of psoriasis require a high daily dosage of 1.0 mg/kg/day, erythrodermic psoriasis should be treated with a lower dosage of 0.25 to 0.35 mg/kg/day. In chronic plaque-like psoriasis, a mean daily dosage of 0.5 mg/kg/day over several weeks to months, usually combined with photo(chemo)therapy, tar or dithranol, is recommended. Other indications for oral etretinate therapy are adequately treated with a moderate dosage of 0.4 to 0.75 mg/kg/day. Etretin differs from etretinate in having a much shorter elimination half-life of 2 to 3 days, in contrast to 80 to 100 days after long term administration of etretinate. Moreover, it has not been shown to increase serum cholesterol levels. However, its clinical efficacy is not yet clearly established. Among the arotinoids

Ultrastructure and /sup 3/H-TdR autoradiography after topical application of aromatic retinoid in guinea pigs

Energy Technology Data Exchange (ETDEWEB)

Ueda, K.; Maruo, M.; Inoue, Y.; Wakabayashi, S. (Kyoto Prefectural Univ. of Medicine (Japan))

1981-12-01

Histological, autoradiographical and electron microscopical investigations were performed on the epidermis of guinea pigs after topical application of 0.1% aromatic retinoid ointment for 7 days. Histologically, the epidermis exhibited a thickening of granular layer and acanthosis, without a prolonged rete ridge. Labelling indices were 3 to 4 times higher than in the control epidermis. Electron microscopically, the nuclei in the spinous and the basal layer were large in size and nucleoli were increased in number. In the cytoplasm, tonofilaments were reduced in number and lots of vacuoles containing less dense amorphous material appeared. Amorphous material was present in the intercellular spaces of the epidermis. Differentiation and proliferation of the epidermis in guinea pigs after topical application of aromatic retinoid showed almost the same response in quantity to the epidermis after topical application of retinoic acid, while the epidermal alternation was slight in degree than in the epidermis after topical application of retinoic acid.

New Chiral Bis-Dipolar 6,6'-Disubstituted-Binaphthol Derivatives for Second-Order Nonlinear Optics

DEFF Research Database (Denmark)

Deussen, Heinz-Josef; Boutton, Carlo; Thorup, Niels

1998-01-01

(S)everal chiral molecules with C-2 symmetry derived from two geometries of the binaphthol (BN) system substituted with different accepters have been synthesized in order to study the possibility of producing noncentrosymmetric crystals formed from these chiral structures. All the molecules possess...... cancel out exactly despite the noncentrosymmetry. The crystal structure of racemic 9,14-dicyanodinaphtho[2,1-d:1',2'-f][1,3]-dioxepin (2b) was found to be centrosymmetric. The new compounds were investigated for second-harmonic generation (including BN derivatives reported earlier) by the Kurtz......-Perry powder test to evaluate the second-order nonlinear optical (NLO) properties of polycrystalline samples. Although chirality ensures noncentrosymmetric crystals, only modest (approximate to 2-methyl-4-nitroaniline) or no nonlinearities were observed in the powder test, For a representative selection...

Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

Directory of Open Access Journals (Sweden)

Lourdes Sánchez-Sevilla

2016-10-01

Full Text Available Abstract Background The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH, by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism. Methods This study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC, and polyamine levels, were determined. Results Pre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also “synchronized” by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids. Conclusions Putrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased

Investigation of the Redox Chemistry of Anthraquinone Derivatives Using Density Functional Theory

Energy Technology Data Exchange (ETDEWEB)

Bachman, Jonathan E.; Curtiss, Larry A.; Assary, Rajeev S.

2014-09-25

Application of density functional calculations to compute electrochemical properties such as redox windows, effect of substitution by electron donating and electron withdrawing groups on redox windows, and solvation free energies for ~50 anthraquinone (AQ) derivatives are presented because of their potential as anolytes in all-organic redox flow batteries. Computations suggest that lithium ions can increase (by ~0.4 V) the reduction potential of anthraquinone due to the lithium ion pairing by forming a Lewis base-Lewis acid complex. To design new redox active species, the substitution by electron donating groups are essential to improve the reduction window of AQ with adequate oxidative stability. For instance, a complete methylation of AQ can improve its reduction window by ~0.4 V. The quantum chemical studies of the ~50 AQ derivatives are used to derive a relationship that connects the computed LUMO energy and the reduction potential that can be applied as a descriptor for screening thousands of AQ derivatives. Our computations also suggest that incorporating oxy-methyl dioxolane substituents in the AQ framework can increase its interaction with non-aqueous solvent and improve its solubility. Thermochemical calculations for likely bond breaking decomposition reactions of un-substituted AQ anions suggest that the dianions are relatively stable in the solution. These studies provide ideal platform to perform further combined experimental and theoretical studies to understand the electrochemical reversibility and solubility of new quinone molecules as energy storage materials.

Synthesis and Bioactivity of N-Benzoyl-N'-[5-(2'-substituted phenyl-2-furoyl] Semicarbazide Derivatives

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Zining Cui

2010-06-01

Full Text Available In order to find novel chitin synthesis inhibitors (CSIs with good activity, benzoylphenylurea, a typical kind of CSIs, was chosen as the lead compound and 15 novel derivatives containing furan moieties were designed by converting the urea linkage of benzoylphenylureas into a semicarbazide and changing the aniline part into furoyl groups. The title compounds were synthesized by the reaction of substituted benzoyl isocyanates with 5-(substituted phenyl-2-furoyl hydrazine, and the structures were confirmed by IR, 1H-NMR, elemental analysis and single crystal X-ray diffraction analyses (compound E2. The bioassay results indicated that the title compounds exhibit good insecticidal activity, especially towards Plutella xylostella L., but had lower fungicidal activity. Inspiringly, the title compounds possessed obvious anticancer activity against human promyelocytic leukemic cell line (HL-60, and some of the title compounds also had activity against human hepatocellular carcinoma cell line (Bel-7402, human gastric carcinoma cell line (BGC-823, and human nasopharyngeal carcinoma cell line (KB. The results indicated that the linkage in the lead compounds was important to the bioactivity and spectra. The modification on the urea linkage is an effective strategy to discover new pesticide and drug candidates.

N-substituted iminodiacetic acids

International Nuclear Information System (INIS)

Nunn, A.; Loberg, M.

1982-01-01

The chemical preparation of several new N-substituted iminodiacetic acid derivatives are described. These compounds when complexed with sup(99m)Tc provide useful radiopharmaceuticals for the external imaging of the hepatobiliary system. (U.K.)

Preparation of 7-substituted ginkgolide derivatives

DEFF Research Database (Denmark)

Vogensen, Stine Byskov; Strømgaard, Kristian; Shindou, Hideo

2003-01-01

alpha-fluoro ginkgolide B was equipotent to ginkgolide B underlining the critical importance of the 7-position of ginkgolides for PAF receptor activity. Herein we describe the synthesis of a series of ginkgolide B derivatives with modifications at the 7-position and the pharmacological evaluation...... of these derivatives as assayed by cloned PAF receptors. In two cases nucleophilic attack on a 7beta-O-triflate ginkgolide B did not lead to the expected products, but gave rise to two unprecedented ginkgolide derivatives, one with a novel rearranged skeleton. Furthermore, standard reduction of 7alpha-azido ginkgolide......-chloro ginkgolide B, the most potent nonaromatic ginkgolide derivative described to date with a K(i) value of 110 nM....

ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments.

Science.gov (United States)

Wu, Yu; Pons, Valérie; Goudet, Amélie; Panigai, Laetitia; Fischer, Annette; Herweg, Jo-Ana; Kali, Sabrina; Davey, Robert A; Laporte, Jérôme; Bouclier, Céline; Yousfi, Rahima; Aubenque, Céline; Merer, Goulven; Gobbo, Emilie; Lopez, Roman; Gillet, Cynthia; Cojean, Sandrine; Popoff, Michel R; Clayette, Pascal; Le Grand, Roger; Boulogne, Claire; Tordo, Noël; Lemichez, Emmanuel; Loiseau, Philippe M; Rudel, Thomas; Sauvaire, Didier; Cintrat, Jean-Christophe; Gillet, Daniel; Barbier, Julien

2017-11-14

Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.

The substitution bias of the consumer price index

OpenAIRE

Frenger, Petter

2006-01-01

Abstract: The paper uses elementary consumer theory to propose an inflation independent ratio definition of the substitution bias of the Laspeyres consumer price index, and derives an approximate substitution bias which depends on the size of the price change as measured by a norm in the Laspeyres plane and on the elasticity of substitution in the direction of the price change. This norm or distance measure can be interpreted as a price substitution index which yields useful in...

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

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Senchuan Song

2013-12-01

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

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

Directory of Open Access Journals (Sweden)

Sándor B. Ötvös

2013-07-01

Full Text Available The preparation of novel multi-substituted 1,2,3-triazole-modified β-aminocyclohexanecarboxylic acid derivatives in a simple and efficient continuous-flow procedure is reported. The 1,3-dipolar cycloaddition reactions were performed with copper powder as a readily accessible Cu(I source. Initially, high reaction rates were achieved under high-pressure/high-temperature conditions. Subsequently, the reaction temperature was lowered to room temperature by the joint use of both basic and acidic additives to improve the safety of the synthesis, as azides were to be handled as unstable reactants. Scale-up experiments were also performed, which led to the achievement of gram-scale production in a safe and straightforward way. The obtained 1,2,3-triazole-substituted β-aminocyclohexanecarboxylates can be regarded as interesting precursors for drugs with possible biological effects.

New assignment of 14N NQR spectral lines for tetrazoles derivatives

Science.gov (United States)

Mamadazizov, Sultonazar; Shelyapina, Marina G.; Kupriyanova, Galina S.; Mozzhukhin, George V.

2018-04-01

In recent years, considerable interest has been shown in the study of tetrazole derivatives, which attract attention as highly nitrogenous compounds for use as an isosteric substitutes for various functional groups that leads to creation of novel biologically active substances. NQR techniques, being sensitive to the local environment of 14N nuclei, provide great opportunities to study these new substances. To make investigation of complex compounds containing tetrazoles derivatives easier and more reliable a correctly assigned 14N NQR spectra of tetrazoles are required. Here we report on the results of our DFT B3LYP calculations of 14N NQR spectral parameters (quadrupole coupling constant Qcc and the asymmetry parameter of the electric field gradient η) for tetrazole, 5-aminotetrazole and 5-aminotetrazole monohydrate. It has been found that the commonly accepted assignment of the 14N NQR spectral lines for these molecules is incorrect. A new assignment for these molecules is proposed.

Ultrasound-Promoted Greener Synthesis of Novel Trifurcate 3-Substituted-chroman-2,4-dione Derivatives and Their Drug-Likeness Evaluation

Directory of Open Access Journals (Sweden)

Yu Xue

2012-11-01

Full Text Available An efficient and convenient approach for one-pot synthesis of 3-substituted chroman-2,4-diones via a three-component reaction of aromatic aldehydes, 4-hydroxy- coumarins and diverse pyrazolone derivatives was described. The combinatorial synthesis for this methodology was achieved by applying ultrasound irradiation in the absence of activator while making use of water as green solvent. Additionally, novel chroman-2,4-dione derivatives attached to an edaravone moiety represent an exploitable source of brand new anticancer agents. In comparison with conventional methods, experimental simplicity, good functional group tolerance, excellent yields, short routine, and atom efficiency are prominent features of this sonocatalyzed procedure.

Spectral, luminescent and lasing properties of pyran derivatives

International Nuclear Information System (INIS)

Kopylova, T N; Svetlichnyi, Valerii A; Samsonova, L G; Svetlichnaya, N N; Reznichenko, A V; Ponomareva, O V; Komlev, I V

2003-01-01

The spectral, luminescent and lasing properties of eight organic molecules, substituted pyrans (DCM), are studied upon pumping by an exciplex XeCl laser at 308 nm and by the second harmonic from a Nd:YAG laser at 532 nm. These molecules exhibit lasing in the red spectral region between 600 and 780 nm with the efficiency of 45%. Lasing was also obtained in bis-substituted pyrans having the quantum yield of fluorescence equal to 0.01. The possibility of preparation of solid active media for tunable lasers based on polymer matrices doped with substituted pyrans is discussed. (active media. lasers)

Fluorine-18-labelled molecules: synthesis and application in medical imaging

International Nuclear Information System (INIS)

Dolle, F.; Perrio, C.; Barre, L.; Lasne, M.C.; Le Bars, D.

2006-01-01

Positron emission tomography (PET) is one of the more powerful available techniques for medical imaging. It relies on the use of molecules labelled with a positron emitter (β + ). Among those emitters, fluorine-18, available from a cyclotron, is a radionuclide of choice because of its relatively long-half-life (109.8 min) and the relatively low energy of the emitted-positron. The electrophilic form of fluorine-18 ([ 18 F]F 2 or reagents derived from [ 18 F]F 2 ) is mainly used for hydrogen or metal substitutions on aromatic or vinylic carbons. The presence of the stable isotope (fluorine-19) in the radiotracers limits their use in medical imaging. The nucleophilic form of fluorine-18 (alkaline mono-fluoride, K[ 18 F]F, the most used), obtained from irradiation of enriched water, is widely used in aliphatic and (hetero)aromatic substitutions for the synthesis of radiotracers with high specific radioactivity. Some examples of radio-fluorinated tracers used in PET are presented, as well as some of their in vivo applications in human. (authors)

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.

Novel Terthiophene-Substituted Fullerene Derivatives as Easily Accessible Acceptor Molecules for Bulk-Heterojunction Polymer Solar Cells

Directory of Open Access Journals (Sweden)

Filippo Nisic

2014-01-01

Full Text Available Five fulleropyrrolidines and methanofullerenes, bearing one or two terthiophene moieties, have been prepared in a convenient way and well characterized. These novel fullerene derivatives are characterized by good solubility and by better harvesting of the solar radiation with respect to traditional PCBM. In addition, they have a relatively high LUMO level and a low band gap that can be easily tuned by an adequate design of the link between the fullerene and the terthiophene. Preliminary results show that they are potential acceptors for the creation of efficient bulk-heterojunction solar cells based on donor polymers containing thiophene units.

2-(1-Adamantyl-1-(3-aminophenylethanol

Directory of Open Access Journals (Sweden)

Michal Rouchal

2011-09-01

Full Text Available In the crystal structure of the title compound, C18H25NO, molecules are linked via O—H...N hydrogen bonds, forming chains parallel to the c axis. Additional weak N—H...O interactions stabilize the crystal packing. The adamantane cage consists of three fused cyclohexane rings in almost ideal chair conformations, with C—C—C angles in the range 107.9 (10–111.3 (11°.

Orthogonal 4,10 and 6,12 substitution of dibenzo[def,mno]chrysene polycyclic aromatic small molecules

KAUST Repository

Koldemir, Unsal; Tinkham, Jonathan S.; Johnson, Robert; Lim, Bogyu; Yemam, Henok A.; Gagnon, Kevin J.; Parkin, Sean; Sellinger, Alan

2017-01-01

A series of new polycyclic aromatic hydrocarbon compounds based on (4,10-disubstituted-dibenzo[def,mno]chrysene-6,12-dione) and 4,10 di-substituted 6,12-bis(triisopropylsilylethynyl)dibenzo[def,mno]chrysene are reported with tunable electronic properties through varied molecular architecture. Starting with an inexpensive commercially available textile dye known as Vat Orange #3, (4,10-dibromo-dibenzo[def,mno] chrysene-6,12-dione) we extended the conjugation at the 4- and 10-positions by the attachment of both electron rich and deficient hexylvinylphthalimide, thiophene, hexylthiophene, triphenylamine, and hexylbithiophene aromatic groups, and studied the resultant optoelectronic properties. By applying various synthetic metal-catalyzed reactions, soluble dibenzo[def,mno]chrysene and dibenzo[def,mno]chrysene-6,12-dione derivatives were achieved with optical edge band gaps between 2.30 eV and 1.65 eV.

Orthogonal 4,10 and 6,12 substitution of dibenzo[def,mno]chrysene polycyclic aromatic small molecules

KAUST Repository

Koldemir, Unsal

2017-07-14

A series of new polycyclic aromatic hydrocarbon compounds based on (4,10-disubstituted-dibenzo[def,mno]chrysene-6,12-dione) and 4,10 di-substituted 6,12-bis(triisopropylsilylethynyl)dibenzo[def,mno]chrysene are reported with tunable electronic properties through varied molecular architecture. Starting with an inexpensive commercially available textile dye known as Vat Orange #3, (4,10-dibromo-dibenzo[def,mno] chrysene-6,12-dione) we extended the conjugation at the 4- and 10-positions by the attachment of both electron rich and deficient hexylvinylphthalimide, thiophene, hexylthiophene, triphenylamine, and hexylbithiophene aromatic groups, and studied the resultant optoelectronic properties. By applying various synthetic metal-catalyzed reactions, soluble dibenzo[def,mno]chrysene and dibenzo[def,mno]chrysene-6,12-dione derivatives were achieved with optical edge band gaps between 2.30 eV and 1.65 eV.

Biological relevance and synthesis of C-substituted morpholine derivatives

NARCIS (Netherlands)

Wijtmans, R.; Vink, M.K.S.; Schoemaker, H.E.; Delft, F.L. van; Blaauw, R.H.; Rutjes, F.P.J.T.

2004-01-01

C-Functionalized morpholines are found in a variety of natural products and biologically active compounds, but have also for other reasons been applied in organic synthesis. This review deals with the biological relevance of C-substituted morpholines, their synthesis and important applications in

Keratoacanthoma centrifugum marginatum: unresponsive to oral retinoid and successfully treated with wide local excision.

Directory of Open Access Journals (Sweden)

Kapildev Das

2010-01-01

Full Text Available We describe a case of a 65-year-old male presenting with a large plaque with a rolled-out interrupted margin, atrophic center, and island of normal skin over the left arm. It grew peripherally with central healing, and there was a history of recurrence after inadequate excision. Investigations ruled out other clin­ical mimickers; namely, squamous cell carcinoma, lupus vulgaris, botryomycosis, and blastomycosis-like pyoderma. Histopathological sections showed irregularly shaped craters filled with keratin and epithelial pearl but no evidence of granuloma or cellular atypia. Clinico­pathological correlation proved the lesion to be keratoacanthoma centrifugum marginatum (KCM, a rare variant of keratoacanthoma, which spreads centrifugally, attains a huge size, and never involutes spontaneously. Treatment of KCM has been a problem always and, in our case, systemic retinoid (acitretin for three months proved ineffective. The patient also had a history of recurrence following surgical intervention previously, necessitating wide excision to achieve complete clearance of tumor cells. Hence, after failure of retinoid therapy, the decision of excision with a 1-centimeter margin was taken and the large defect was closed by a split thickness skin graft. The graft uptake was satisfactory, and the patient is being followed-up presently and shows no signs of recurrence after six months, highlighting wide local excision as a useful treatment option.

Structure-charge mobility relation for hexabenzocoronene derivatives

Energy Technology Data Exchange (ETDEWEB)

Kirkpatrick, James [Max Planck Institute for Polymer Research, Ackermannweg 10, Mainz 55128 (Germany); Department of Physics, Imperial College London, Prince Consort Road, London SW7 2BW (United Kingdom); Marcon, Valentina; Kremer, Kurt [Max Planck Institute for Polymer Research, Ackermannweg 10, Mainz 55128 (Germany); Nelson, Jenny [Department of Physics, Imperial College London, Prince Consort Road, London SW7 2BW (United Kingdom); Andrienko, Denis

2008-05-15

Charge mobilities of several derivatives of discotic liquid crystals have been determined by combining three methods into one scheme: (i) quantum chemical methods for the calculation of molecular electronic structures and reorganization energies (ii) molecular dynamics for simulation of the relative positions and orientations of molecules in a columnar mesophase, and (iii) kinetic Monte Carlo simulations and Master Equation approach to simulate charge transport. Applying this scheme to differently substituted hexabenzocoronene derivatives we reproduce the trends and magnitudes of mobilities as measured by pulse-radiolysis time-resolved microwave conductivity (PR-TRMC) and connect mobility directly to the microscopic morphology of the columns. Our study also shows that it is possible to understand and reproduce experimental charge transport parameters, and, in some cases, accurately predict them. (copyright 2008 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Pyridine substituted spirofluorene derivative as an electron transport material for high efficiency in blue organic light-emitting diodes

Energy Technology Data Exchange (ETDEWEB)

Jeon, Soon Ok; Yook, Kyoung Soo; Lee, Jun Yeob, E-mail: leej17@dankook.ac.k

2010-11-01

The quantum efficiency of blue fluorescent organic light-emitting diodes was enhanced by 20% using a pyridine substituted spirofluorene-benzofluorene derivative as an electron transport material. 2',7'-Di(pyridin-3-yl)spiro[benzofluorene-7,9'-fluorene] (SPBP) was synthesized and it was used as the electron transport material to block the hole leakage from the emitting layer. The improvement of the quantum efficiency and power efficiency of the blue fluorescent organic light-emitting diodes using the SPBP was investigated.

Ultrastructure and /sup 3/H-TdR autoradiogram in the skin of guinea pigs after topical application of aromatic retinoid (Ro 10-9359)

Energy Technology Data Exchange (ETDEWEB)

Ueda, K.; Inoue, Y.; Wakabayashi, S.; Kitamura, T. (Kyoto Prefectural Univ. of Medicine (Japan))

1982-01-01

The effect of topical application with 0.1% aromatic retinoid ointment for 7 days on quinea pig epidermis were investigated histologically, electron microscopically and autoradiographically. 1. Histological changes of the epidermis after topical application of aromatic retinoid were characterized by acanthosis and thickening of epidermal layer without prolonged rete ridge. Epidermal cells were stained slightly positive with alcian blue. 2. Labelling index in epidermis was 18% high in average rate, and labelled cells distributed in basal layer and 2 to 3 upper basal layers. Labelling index was 3 to 4 times higher than in control skin. 3. Ultrastructural changes were observed in nuclei and cytoplasm of epidermal cells. Nuclei were large in size and irregular in shape, and nucleoli were large in size and increased in number. In the cytoplasm, tonofilament was reduced in number and lots of vacuoles containing less dense material appeared. Mitochondria, endoplasmic reticulum and ribosomes were rich in number. In the intercellular spaces, amorphous less dense materials were seen. Desmosomes were kept in figure and were floating in the wide intercellular spaces. 4. Differentiation and proliferation of the epidermis in guinea pig after topical application of aromatic retinoid and retinoic acid were almost same in quality of the reaction, but the reaction was different in quantity between both agents.

[Immunosuppresive agents, retinoids and new trends in the therapy of psoriasis].

Science.gov (United States)

Svozil, M

2002-11-01

Some psoriasis forms can be successfully treated with topical medicaments; serious and extensive forms cannot be cured without systemic treatment with retinoids (etretinate, acitretin, tazarotene) or with immunosuppressives (methotrexate, cyclosporine A, tacrolimus, SDZ 281-240). Immunotherapy and nucleotide analogues are being newly introduced, a number of potentially effective substances interfering with pathogenetic mechanisms participating in the emergence and self-prolongation of psoriasis are in the stage of research and clinical trials, and gene therapy possibilities are being investigated. The development and testing of drugs serving therapy for psoriasis correlates with the development of knowledge about the origins of the disease and the mechanisms of how antipsoriatics in current use as well as the new potential ones work.

Nonpeptidic angiotensin II AT₁ receptor antagonists derived from 6-substituted aminocarbonyl and acylamino benzimidazoles.

Science.gov (United States)

Zhang, Jun; Wang, Jin-Liang; Yu, Wei-Fa; Zhou, Zhi-Ming; Tao, Wen-Chang; Wang, Yi-Cheng; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, Xiao-Feng; Fei, Fan; Liu, Ting; Liang, Ai-Hua

2013-11-01

Both 6-substituted aminocarbonyl and acylamino benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT₁ receptor antagonists. Compounds 6f, 6g, 11e, 11f, 11g, and 12 showed nanomolar AT₁ receptor binding affinity and high AT₁ receptor selectivity over AT₂ receptor in a preliminary pharmacological evaluation. Among them, the two most active compounds 6f (AT₁ IC₅₀ = 3 nM, AT₂ IC₅₀ > 10,000 nM, PA₂ = 8.51) and 11g (AT₁ IC₅₀ = 0.1 nM, AT₂ IC₅₀ = 149 nM, PA₂ = 8.43) exhibited good antagonistic activity in isolated rabbit aortic strip functional assay. In addition, they were orally active AT₁ receptor antagonists in spontaneous hypertensive rats. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Antimalarial Activity of C-10 Substituted Triazolyl Artemisinin.

Science.gov (United States)

Park, Gab-Man; Park, Hyun; Oh, Sangtae; Lee, Seokjoon

2017-12-01

We synthesized C-10 substituted triazolyl artemisinins by the Huisgen cycloaddition reaction between dihydroartemisinins (2) and variously substituted 1, 2, 3-triazoles (8a-8h). The antimalarial activities of 32 novel artemisinin derivatives were screened against a chloroquine-resistant parasite. Among them, triazolyl artemisinins with electron-withdrawing groups showed stronger antimalarial activities than those shown by the derivatives having electron-donating groups. In particularly, m-chlorotriazolyl artemisinin (9d-12d) showed antimalarial activity equivalent to that of artemisinin and could be a strong drug candidate.

Combination Superficial Peels With Salicylic Acid and Post-Peel Retinoids.

Science.gov (United States)

Kligman, Douglas E; Draelos, Zoe D

2016-04-01

Salicylic acid (SA) and retinoids, tretinoin (all-trans retinoic acid [ATRA]), and retinol (all-trans retinol) are widely used as topical agents for the improvement of photodamage and acne vulgaris. They can be used in daily take-home products or as part of an in-office procedure, combining the benefits of a keratolytic (SA) and a retinoid. The objective of this research was to compare the efficacy for ameliorating photodamage of topical tretinoin (0.25%) and retinol (0.25%) to baseline and with each other when applied after a 30% salicylic acid peel on human facial skin. Twenty female subjects received a full face 30% SA peel followed by the overnight application of tretinoin to a 1 randomized half-face and retinol to the opposite side (split-face study). The identical procedure was repeated at week 2. Double-blinded subject and investigator assessments of the results were captured at weeks 2 and 4. By investigator evaluation, both peeling regimens were effective in improving photodamage parameters compared to baseline. (ATRA P-values at week 4 were: P=.00008 texture, P=.00013 roughness, P=.00221 pores, P=.00098 dryness, P=.02770 erythema, and P=.00008 overall appearance. Retinol P-values at week 4 were: P=.00019 texture, P=.00053 roughness, P=.00221 pores, P=.00147 dryness, P=.02770 erythema, and P=.0043 overall appearance.) By subject self-assessment compared with baseline, both tretinoin and retinol were effective in improving overall appearance (ATRA P=.0229 and retinol P=.0190). By investigator evaluation comparing tretinoin with retinol, tretinoin was slightly better than retinol at week 4 in improving texture P=.00506, roughness P=.01171, and overall appearance P=.00506. By subject self-assessment comparing tretinoin with retinol, there was no difference in overall appearance (ATRA P=.2367 and retinol P=.3613). Either topical tretinoin (0.25%) or retinol (0.25%) can be used safely and effectively when applied in office immediately after SA peeling to

Synthesis of Substituted α-Trifluoromethyl Piperidinic Derivatives

Directory of Open Access Journals (Sweden)

Sarah Rioton

2017-03-01

Full Text Available A comprehensive survey of pathways leading to the generation of α-trifluoromethyl monocyclic piperidinic derivatives is provided (65 references. These compounds have been synthesized either from 6-membered rings e.g., pipecolic acid or lactam derivatives by introduction a trifluoromethyl group, from pyridine or pyridinone derivatives by reduction, and from 5-membered rings e.g., prolinol derivatives by ring expansion, from linear amines by cyclization or from dienes/dienophiles by [4 + 2]-cycloaddition.

Atomic force microscope observation of branching in single transcript molecules derived from human cardiac muscle

International Nuclear Information System (INIS)

Reed, Jason; Hsueh, Carlin; Gimzewski, James K; Mishra, Bud

2008-01-01

We have used an atomic force microscope to examine a clinically derived sample of single-molecule gene transcripts, in the form of double-stranded cDNA, (c: complementary) obtained from human cardiac muscle without the use of polymerase chain reaction (PCR) amplification. We observed a log-normal distribution of transcript sizes, with most molecules being in the range of 0.4-7.0 kilobase pairs (kb) or 130-2300 nm in contour length, in accordance with the expected distribution of mRNA (m: messenger) sizes in mammalian cells. We observed novel branching structures not previously known to exist in cDNA, and which could have profound negative effects on traditional analysis of cDNA samples through cloning, PCR and DNA sequencing

An Ursolic Acid Derived Small Molecule Triggers Cancer Cell Death through Hyperstimulation of Macropinocytosis.

Science.gov (United States)

Sun, Lin; Li, Bin; Su, Xiaohui; Chen, Ge; Li, Yaqin; Yu, Linqian; Li, Li; Wei, Wanguo

2017-08-10

Macropinocytosis is a transient endocytosis that internalizes extracellular fluid and particles into vacuoles. Recent studies suggest that hyperstimulation of macropinocytosis can induce a novel nonapoptotic cell death, methuosis. In this report, we describe the identification of an ursolic acid derived small molecule (compound 17), which induces cancer cell death through hyperstimulation of macropinocytosis. 17 causes the accumulation of vacuoles derived from macropinosomes based on transmission electron microscopy, time-lapse microscopy, and labeling with extracellular fluid phase tracers. The vacuoles induced by 17 separate from other cytoplasmic compartments but acquire some characteristics of late endosomes and lysosomes. Inhibiting hyperstimulation of macropinocytosis with the specific inhibitor amiloride blocks cell death, implicating that 17 leads to cell death via macropinocytosis, which is coincident with methuosis. Our results uncovered a novel cell death pathway involved in the activity of 17, which may provide a basis for further development of natural-product-derived scaffolds for drugs that trigger cancer cell death by methuosis.

Medium-Bandgap Small-Molecule Donors Compatible with Both Fullerene and Nonfullerene Acceptors.

Science.gov (United States)

Huo, Yong; Yan, Cenqi; Kan, Bin; Liu, Xiao-Fei; Chen, Li-Chuan; Hu, Chen-Xia; Lau, Tsz-Ki; Lu, Xinhui; Sun, Chun-Lin; Shao, Xiangfeng; Chen, Yongsheng; Zhan, Xiaowei; Zhang, Hao-Li

2018-03-21

Much effort has been devoted to the development of new donor materials for small-molecule organic solar cells due to their inherent advantages of well-defined molecular weight, easy purification, and good reproducibility in photovoltaic performance. Herein, we report two small-molecule donors that are compatible with both fullerene and nonfullerene acceptors. Both molecules consist of an (E)-1,2-di(thiophen-2-yl)ethane-substituted (TVT-substituted) benzo[1,2-b:4,5-b']dithiophene (BDT) as the central unit, and two rhodanine units as the terminal electron-withdrawing groups. The central units are modified with either alkyl side chains (DRBDT-TVT) or alkylthio side chains (DRBDT-STVT). Both molecules exhibit a medium bandgap with complementary absorption and proper energy level offset with typical acceptors like PC 71 BM and IDIC. The optimized devices show a decent power conversion efficiency (PCE) of 6.87% for small-molecule organic solar cells and 6.63% for nonfullerene all small-molecule organic solar cells. Our results reveal that rationally designed medium-bandgap small-molecule donors can be applied in high-performance small-molecule organic solar cells with different types of acceptors.

Synthesis of 3-(4, 5-dihydro-1-phenyl-5-substituted phenyl-1H-pyrazol-3-yl-2H-chromen-2-one derivatives and evaluation of their anticancer activity

Directory of Open Access Journals (Sweden)

Nitin Kumar

2017-05-01

Full Text Available A novel series of 3-(4, 5-dihydro-1-phenyl-5-substituted phenyl-1H-pyrazol-3-yl-2H-chromen-2-one derivatives were synthesized. In the first step salicylaldehyde was reacted with ethylacetoacetate at room temperature by stirring which gives compound (I. Compound (I when refluxed with substituted benzaldehyde and diethylamine in the presence of n-butanol for 4–5 h gives substituted derivatives (IIa–d. Compounds synthesized in step 2 when refluxed with phenyl hydrazine in the presence of pyridine for 6–7 h gives the title compounds (IIIa–d. All the synthesized compounds were sent to NCI for anticancer activity. Synthesized compounds were tested for anticancer activity against 60 different cell lines. From the data thus obtained it was observed that simple coumarin ring derivatives were more effective in inhibiting the growth of cancerous cell lines, than coumarin-pyrazoline derivatives. Among all the synthesized compounds, irrespective of compounds having simple coumarin ring and coumarin-pyrazoline combination, compounds IIa–c, IIIb and IIId were potent anticancer agents. Compounds were active for the single dose therapeutic program at the dose of 1.00E-5 molar concentration. The main anti cancer activity is assumed to be due to the presence of the lactone structure in coumarin moiety.

Synthesis, crystal structure, and transport properties of Fe substituted rhombohedral skutterudite derivatives Co4−xFexGe6Se6

KAUST Repository

Wei, Kaya

2014-11-01

We report on the synthesis and low temperature transport properties of rhombohedral derivatives of the cubic skutterudite CoSb3, namely Co4-xFexGe6Se6 with x = 0, 1, 1.5. Rietveld refinement and elemental analyses were used to identify the structure and stoichiometry of the compositions. The thermal conductivity was investigated by employing the Debye model with different phonon-scattering parameters. This investigation demonstrates that Fe substitution is feasible in these skutterudite derivatives and can significantly affect the transport properties as compared with Co4Ge6Se6. © 2014 Elsevier B.V. All rights reserved.

Synthesis, crystal structure, and transport properties of Fe substituted rhombohedral skutterudite derivatives Co4−xFexGe6Se6

KAUST Repository

Wei, Kaya; Dong, Yongkwan; Puneet, Pooja; Tritt, Terry M.; Nolas, George S.

2014-01-01

We report on the synthesis and low temperature transport properties of rhombohedral derivatives of the cubic skutterudite CoSb3, namely Co4-xFexGe6Se6 with x = 0, 1, 1.5. Rietveld refinement and elemental analyses were used to identify the structure and stoichiometry of the compositions. The thermal conductivity was investigated by employing the Debye model with different phonon-scattering parameters. This investigation demonstrates that Fe substitution is feasible in these skutterudite derivatives and can significantly affect the transport properties as compared with Co4Ge6Se6. © 2014 Elsevier B.V. All rights reserved.

Convergent synthesis of 6-substituted phenanthridines via anionic ring closure

DEFF Research Database (Denmark)

Lysén, M.; Kristensen, Jesper Langgaard; Vedsø, P.

2002-01-01

Chemical equation presented The addition of organometallic derivatives to the cyano group of 2-(2-fluorophenyl)benzonitrile followed by intramolecular nucleophilic substitution produces 6-substituted phenanthridines. Alkyllithiums, aryllithiums, and sterically nondemanding lithium amides reacted ...

Exploring the potential of high resolution mass spectrometry for the investigation of lignin-derived phenol substitutes in phenolic resin syntheses.

Science.gov (United States)

Dier, Tobias K F; Fleckenstein, Marco; Militz, Holger; Volmer, Dietrich A

2017-05-01

Chemical degradation is an efficient method to obtain bio-oils and other compounds from lignin. Lignin bio-oils are potential substitutes for the phenol component of phenol formaldehyde (PF) resins. Here, we developed an analytical method based on high resolution mass spectrometry that provided structural information for the synthesized lignin-derived resins and supported the prediction of their properties. Different model resins based on typical lignin degradation products were analyzed by electrospray ionization in negative ionization mode. Utilizing enhanced mass defect filter techniques provided detailed structural information of the lignin-based model resins and readily complemented the analytical data from differential scanning calorimetry and thermogravimetric analysis. Relative reactivity and chemical diversity of the phenol substitutes were significant determinants of the outcome of the PF resin synthesis and thus controlled the areas of application of the resulting polymers. Graphical abstract ᅟ.

Theoretical study of stability and charge-transport properties of coronene molecule and some of its halogenated derivatives: A path to ambipolar organic-based materials?

Energy Technology Data Exchange (ETDEWEB)

Sancho-García, J. C., E-mail: jc.sancho@ua.es; Pérez-Jiménez, A. J., E-mail: aj.perez@ua.es [Departamento de Química Física, Universidad de Alicante, E-03080 Alicante (Spain)

2014-10-07

We have carefully investigated the structural and electronic properties of coronene and some of its fluorinated and chlorinated derivatives, including full periphery substitution, as well as the preferred orientation of the non-covalent dimer structures subsequently formed. We have paid particular attention to a set of methodological details, to first obtain single-molecule magnitudes as accurately as possible, including next the use of modern dispersion-corrected methods to tackle the corresponding non-covalently bound dimers. Generally speaking, this class of compounds is expected to self-assembly in neighboring π-stacks with dimer stabilization energies ranging from –20 to –30 kcal mol{sup −1} at close distances around 3.0–3.3 Å. Then, in a further step, we have also calculated hole and electron transfer rates of some suitable candidates for ambipolar materials, and corresponding charge mobility values, which are known to critically depend on the supramolecular organization of the samples. For coronene and per-fluorinated coronene, we have found high values for their hopping rates, although slightly smaller for the latter due to an increase (decrease) of the reorganization energies (electronic couplings)

The kinetic energy operator for distance-dependent effective nuclear masses: Derivation for a triatomic molecule.

Science.gov (United States)

Khoma, Mykhaylo; Jaquet, Ralph

2017-09-21

The kinetic energy operator for triatomic molecules with coordinate or distance-dependent nuclear masses has been derived. By combination of the chain rule method and the analysis of infinitesimal variations of molecular coordinates, a simple and general technique for the construction of the kinetic energy operator has been proposed. The asymptotic properties of the Hamiltonian have been investigated with respect to the ratio of the electron and proton mass. We have demonstrated that an ad hoc introduction of distance (and direction) dependent nuclear masses in Cartesian coordinates preserves the total rotational invariance of the problem. With the help of Wigner rotation functions, an effective Hamiltonian for nuclear motion can be derived. In the derivation, we have focused on the effective trinuclear Hamiltonian. All necessary matrix elements are given in closed analytical form. Preliminary results for the influence of non-adiabaticity on vibrational band origins are presented for H 3 + .

Structure-Activity Relationships of Truncated C2- or C8-Substituted Adenosine Derivatives as Dual Acting A2A and A3 Adenosine Receptor Ligands

Science.gov (United States)

Hou, Xiyan; Majik, Mahesh S.; Kim, Kyunglim; Pyee, Yuna; Lee, Yoonji; Alexander, Varughese; Chung, Hwa-Jin; Lee, Hyuk Woo; Chandra, Girish; Lee, Jin Hee; Park, Seul-gi; Choi, Won Jun; Kim, Hea Ok; Phan, Khai; Gao, Zhan-Guo; Jacobson, Kenneth A.; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin

2011-01-01

Truncated N6-substituted-4′-oxo- and 4′-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A2A and A3 adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA2AAR, but hydrophobic C8 substitution abolished binding at the hA2AAR. However, most of synthesized compounds displayed medium to high binding affinity at the hA3AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA2AAR agonists. C2 substitution probed geometrically through hA2AAR-docking, was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA2AAR agonist and hA3AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases. PMID:22142423

Synthesis of Novel Benzimidazolyl-substituted Acrylonitriles and Amidino-substituted Benzimidazo[1,2-a]Quinolines

Directory of Open Access Journals (Sweden)

Grace Karminski-Zamola

2006-08-01

Full Text Available A series of novel benzimidazole derivatives 3-10 were synthesized. Benzimidazolyl-substituted acrylonitriles 3 and 4 underwent a photochemical dehydrocyclization reaction to give the corresponding mono- and dicyano-substituted benzimidazo[1,2-a] quinolines 5 and 6. Pinner reaction of these compounds did not give the expected mono- and diamidines, but rather only compounds 7-10, with amido groups at 6-position were isolated. A mechanism for the reaction is proposed. Acyclic compounds 3 and 4, as well as cyclic benzimidazo[1,2-a]quinolines 5-8, exhibit interesting spectroscopic properties and are potential biologically active compounds.

Symbolic derivation of high-order Rayleigh-Schroedinger perturbation energies using computer algebra: Application to vibrational-rotational analysis of diatomic molecules

Energy Technology Data Exchange (ETDEWEB)

Herbert, John M. [Kansas State Univ., Manhattan, KS (United States). Dept. of Chemistry

1997-01-01

Rayleigh-Schroedinger perturbation theory is an effective and popular tool for describing low-lying vibrational and rotational states of molecules. This method, in conjunction with ab initio techniques for computation of electronic potential energy surfaces, can be used to calculate first-principles molecular vibrational-rotational energies to successive orders of approximation. Because of mathematical complexities, however, such perturbation calculations are rarely extended beyond the second order of approximation, although recent work by Herbert has provided a formula for the nth-order energy correction. This report extends that work and furnishes the remaining theoretical details (including a general formula for the Rayleigh-Schroedinger expansion coefficients) necessary for calculation of energy corrections to arbitrary order. The commercial computer algebra software Mathematica is employed to perform the prohibitively tedious symbolic manipulations necessary for derivation of generalized energy formulae in terms of universal constants, molecular constants, and quantum numbers. As a pedagogical example, a Hamiltonian operator tailored specifically to diatomic molecules is derived, and the perturbation formulae obtained from this Hamiltonian are evaluated for a number of such molecules. This work provides a foundation for future analyses of polyatomic molecules, since it demonstrates that arbitrary-order perturbation theory can successfully be applied with the aid of commercially available computer algebra software.

High-resolution spectroscopy in superfluid helium droplets. Investigation of vibrational fine structures in electronic spectra of phthalocyanine and porphyrin derivatives

Energy Technology Data Exchange (ETDEWEB)

Riechers, Ricarda Eva Friederike Elisabeth

2011-03-22

Since a considerably large variety of substituted compounds is commercially available and the electronic excitation spectra fit well into the spectral range covered by the continuous wave dye laser used for this study several porphyrin and phthalocyanine derivatives substituted with different types and numbers of alkyl and aryl groups were chosen as molecular probes. Recording fluorescence excitation and dispersed emission spectra revealed exclusively sharp transitions for all species. A change of the molecule's electrostatic moments, primarily and most effectively, a change of the molecular dipole moment regarding both magnitude and orientation, was identified as the main contribution for line broadening effects. Apart from the sharp lines presented in their fluorescence excitation spectra, the phthalocyanine derivatives investigated for this study, namely chloro-aluminium-phthalocyanine (AlClPc) and tetra-tertbutyl-phthalocyanine (TTBPc), exhibited more than one emission spectrum.

High-resolution spectroscopy in superfluid helium droplets. Investigation of vibrational fine structures in electronic spectra of phthalocyanine and porphyrin derivatives

International Nuclear Information System (INIS)

Riechers, Ricarda Eva Friederike Elisabeth

2011-01-01

Since a considerably large variety of substituted compounds is commercially available and the electronic excitation spectra fit well into the spectral range covered by the continuous wave dye laser used for this study several porphyrin and phthalocyanine derivatives substituted with different types and numbers of alkyl and aryl groups were chosen as molecular probes. Recording fluorescence excitation and dispersed emission spectra revealed exclusively sharp transitions for all species. A change of the molecule's electrostatic moments, primarily and most effectively, a change of the molecular dipole moment regarding both magnitude and orientation, was identified as the main contribution for line broadening effects. Apart from the sharp lines presented in their fluorescence excitation spectra, the phthalocyanine derivatives investigated for this study, namely chloro-aluminium-phthalocyanine (AlClPc) and tetra-tertbutyl-phthalocyanine (TTBPc), exhibited more than one emission spectrum.

Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

Institute of Scientific and Technical Information of China (English)

Weiliang Zhao; Dezhi Kang; Yuanxiang Lin

2008-01-01

BACKGROUND: Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE: To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY: A computer-based online search was conducted in PUBMED for English language publications containing the key words "brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor" from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria: ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS: After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these

A novel dihydropyridine with 3-aryl meta-hydroxyl substitution blocks L-type calcium channels in rat cardiomyocytes

International Nuclear Information System (INIS)

Galvis-Pareja, David; Zapata-Torres, Gerald; Hidalgo, Jorge; Ayala, Pedro

2014-01-01

Rationale: Dihydropyridines are widely used for the treatment of several cardiac diseases due to their blocking activity on L-type Ca 2+ channels and their renowned antioxidant properties. Methods: We synthesized six novel dihydropyridine molecules and performed docking studies on the binding site of the L-type Ca 2+ channel. We used biochemical techniques on isolated adult rat cardiomyocytes to assess the efficacy of these molecules on their Ca 2+ channel-blocking activity and antioxidant properties. The Ca 2+ channel-blocking activity was evaluated by confocal microscopy on fluo-3AM loaded cardiomyocytes, as well as using patch clamp experiments. Antioxidant properties were evaluated by flow cytometry using the ROS sensitive dye 1,2,3 DHR. Results: Our docking studies show that a novel compound with 3-OH substitution inserts into the active binding site of the L-type Ca 2+ channel previously described for nitrendipine. In biochemical assays, the novel meta-OH group in the aryl in C4 showed a high blocking effect on L-type Ca 2+ channel as opposed to para-substituted compounds. In the tests we performed, none of the molecules showed antioxidant properties. Conclusions: Only substitutions in C2, C3 and C5 of the aryl ring render dihydropyridine compounds with the capacity of blocking LTCC. Based on our docking studies, we postulate that the antioxidant activity requires a larger group than the meta-OH substitution in C2, C3 or C5 of the dihydropyridine ring. - Highlights: • Dihydropyridine (DHP) molecules are widely used in cardiovascular disease. • DHPs block Ca 2+ entry through LTCC—some DHPs have antioxidant activity as well. • We synthesized 6 new DHPs and tested their Ca 2+ blocking and antioxidant activities. • 3-Aryl meta-hydroxyl substitution strongly increases their Ca 2+ blocking activity. • 3-Aryl meta-hydroxyl substitution did not affect the antioxidant properties

Insight into the structural requirement of substituted quinazolinone biphenyl acylsulfonamides derivatives as Angiotensin II AT1 receptor antagonist: 2D and 3D QSAR approach

Directory of Open Access Journals (Sweden)

Mukesh C. Sharma

2014-01-01

Full Text Available A series of 19 molecules substituted quinazolinone biphenyl acylsulfonamides derivatives displaying variable inhibition of Angiotensin II receptor AT1 activity were selected to develop models for establishing 2D and 3D QSAR. The compounds in the selected series were characterized by spatial, molecular and electro topological descriptors using QSAR module of Molecular Design Suite (VLife MDS™ 3.5. The best 2D QSAR model was selected, having correlation coefficient r2 (0.8056 and cross validated squared correlation coefficient q2 (0.6742 with external predictive ability of pred_r2 0.7583 coefficient of correlation of predicted data set (pred_r2se 0.2165. The results obtained from QSAR studies could be used in designing better Ang II activity among the congeners in future. The optimum QSAR model showed that the parameters SsssCHE index, SddCE-index, T_2_Cl_4, and SssNHE-index contributed in the model. 3D QSAR analysis by kNN-molecular field analysis approach developed based on principles of the k-nearest neighbor method combined with Genetic algorithms, stepwise forward variable selection approach; a leave-one-out cross-validated correlation coefficient (q2 of 0.6516 and a non-cross-validated correlation coefficient (r2 of 0.8316 and pred_r2 0.6954 were obtained. Contour maps using this approach showed that steric, electrostatic, and hydrophobic field effects dominantly determine binding affinities. The information rendered by 3D QSAR models may lead to a better understanding of structural requirements of Angiotensin II receptor and can help in the design of novel potent antihypertensive molecules.

Eosin-sensitized photooxidation of substituted phenylalanines and tyrosines

Energy Technology Data Exchange (ETDEWEB)

Rizzuto, F.; Spikes, J.D.

1977-01-01

The cosin-sensitized photooxidation of tyrosine and a number of compounds related to tyrosine (substituted phenylalanines) was studied by steady-state kinetic and flash photolysis techniques. In particular, the role of the phenolic group and the amino and carboxyl groups of the alanyl side chain in the photooxidation mechanism was investigated in detail. Several relationships between substrate structure and susceptibility to photooxidation as well as effects of substrate structure on photooxidation mechanisms were found. For example, phenylalanine is not photooxidizable, but substitution of electron-donating (activating) groups such as -OH (as in tyrosine) or -NH/sub 2/ (as in p-aminophenylalanine) results in rapidly photooxidized derivatives. However, substituting deactivating groups such as -Cl (as in p-chlorophenylalanine) or weakly activating groups such as -OCH/sub 3/ (as in 4-methoxyphenylalanine) result in non-photooxidizable derivatives. Substitution of additional activating groups to the ring of hydroxy-substituted phenylalanines results in increased rates of photooxidation, whereas additional deactivating groups result in decreased photooxidation rates. The rate-determining step in the photooxidation mechanism is shown to be dependent on the presence and position of an electron-donating substituent on the benzenoid ring. Only minor involvement of the side chain amino and carboxyl groups was found. Both singlet oxygen and hydrogen abstraction mechanisms are involved in the eosin-sensitized photooxidation of hydroxy-substituted phenylalanines (e.g., tyrosine). The hydrogen abstraction mechanism probably predominates at both pH 8 and 11.

pn-Heterojunction effects of perylene tetracarboxylic diimide derivatives on pentacene field-effect transistor.

Science.gov (United States)

Yu, Seong Hun; Kang, Boseok; An, Gukil; Kim, BongSoo; Lee, Moo Hyung; Kang, Moon Sung; Kim, Hyunjung; Lee, Jung Heon; Lee, Shichoon; Cho, Kilwon; Lee, Jun Young; Cho, Jeong Ho

2015-01-28

We investigated the heterojunction effects of perylene tetracarboxylic diimide (PTCDI) derivatives on the pentacene-based field-effect transistors (FETs). Three PTCDI derivatives with different substituents were deposited onto pentacene layers and served as charge transfer dopants. The deposited PTCDI layer, which had a nominal thickness of a few layers, formed discontinuous patches on the pentacene layers and dramatically enhanced the hole mobility in the pentacene FET. Among the three PTCDI molecules tested, the octyl-substituted PTCDI, PTCDI-C8, provided the most efficient hole-doping characteristics (p-type) relative to the fluorophenyl-substituted PTCDIs, 4-FPEPTC and 2,4-FPEPTC. The organic heterojunction and doping characteristics were systematically investigated using atomic force microscopy, 2D grazing incidence X-ray diffraction studies, and ultraviolet photoelectron spectroscopy. PTCDI-C8, bearing octyl substituents, grew laterally on the pentacene layer (2D growth), whereas 2,4-FPEPTC, with fluorophenyl substituents, underwent 3D growth. The different growth modes resulted in different contact areas and relative orientations between the pentacene and PTCDI molecules, which significantly affected the doping efficiency of the deposited adlayer. The differences between the growth modes and the thin-film microstructures in the different PTCDI patches were attributed to a mismatch between the surface energies of the patches and the underlying pentacene layer. The film-morphology-dependent doping effects observed here offer practical guidelines for achieving more effective charge transfer doping in thin-film transistors.

Synthesis, characterization and serum albumin binding studies of vitamin K3 derivatives.

Science.gov (United States)

Suganthi, Murugesan; Elango, Kuppanagounder P

2017-01-01

Synthesis, characterization and bovine serum albumin (BSA) binding properties of three derivatives of vitamin K3 have been described. Results of UV-Vis and fluorescence spectra indicate complexation between BSA and the ligands with conformational changes in protein, which is strongly supported by synchronous and three dimensional fluorescence studies. Addition of the ligands quenches the fluorescence of BSA which is accompanied by reduction in quantum yield (Ф) from 0.1010 to 0.0775-0.0986 range. Thermodynamic investigations reveal that hydrophobic interaction is the major binding force in the spontaneous binding of these ligands with BSA. The binding constants obtained depend on the substituent present in the quinone ring, which correlates linearly with the Taft's field substituent constant (σ F ). The results show that compound with strong electron withdrawing nitro-group forms relatively stronger complex with BSA than amino and thioglycolate substituted ones. Circular dichroism studies show that the α-helical content of the protein, upon complexation with the ligands, decreases in the case of amino and nitro substituted vitamin K3 while increases in thioglycolate substituted compound. Molecular docking studies indicated that the vitamin K3 derivatives are surrounded by hydrophobic residues of the BSA molecule, which is in good agreement with the results of fluorescence spectral and thermodynamic studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of structure and number of heteroatom on the π-π stacking inte-ractions of benzene with N-substituted coronenes: A theoretical study

Directory of Open Access Journals (Sweden)

Pouya Karimi

2014-07-01

Full Text Available Stability of the π-π stacking interactions in the Ben||N-substituted-coronene complexes was stu-died using the computational quantum chemistry methods (where Ben is benzene and || denotes π-π stacking interaction, and N-substituted-coronene is coronene molecule which substituted with different number of N atoms. The results reveal simultaneous effects of structure and number of Heteroatom on the π-π stacking interactions with N-substituted-coronenes. Changing the number of Heteroatom N in N-substituted-coronenes and substitution of 8N-coronene with electron-withdrawing or electron-donating X groups alter the electron charge density at rings of this molecule and leads to different binding energies in the Ben||X-8N-substituted-coronene com-plexes. Results indicate that electron-withdrawing groups lead to higher π–π stacking binding energies compared to electron-donating ones in the Ben||X-8N-substituted-coronene complexes.

Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy

DEFF Research Database (Denmark)

Rudolf, Gabrielle; Lesca, Gaetan; Mehrjouy, Mana M

2016-01-01

nuclear receptor (RORβ), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment...... in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan...

Si-substituted hydroxyapatite nanopowders: Synthesis, thermal stability and sinterability

International Nuclear Information System (INIS)

Bianco, Alessandra; Cacciotti, Ilaria; Lombardi, Mariangela; Montanaro, Laura

2009-01-01

Synthetic hydroxyapatites incorporating small amounts of Si have shown improved biological performances in terms of enhanced bone apposition, bone in-growth and cell-mediated degradation. This paper reports a systematic investigation on Si-substituted hydroxyapatite (Si 1.40 wt%) nanopowders produced following two different conventional wet methodologies: (a) precipitation of Ca(NO 3 ) 2 .4H 2 O and (b) titration of Ca(OH) 2 . The influence of the synthesis process on composition, thermal behaviour and sinterability of the resulting nanopowders is studied. Samples were characterised by electron microscopy, induced coupled plasma atomic emission spectroscopy, thermal analysis, infrared spectroscopy, N 2 adsorption measurements, X-ray diffraction and dilatometry. Semicrystalline Si-substituted hydroxyapatite powders made up of needle-like nanoparticles were obtained, the specific surface area ranged between 84 and 110 m 2 /g. Pure and Si-substituted hydroxyapatite nanopowders derived from Ca(NO 3 ) 2 .4H 2 O decomposed around 1000 deg. C. Si-substituted hydroxyapatite nanopowders obtained from Ca(OH) 2 were thermally stable up to 1200 deg. C and showed a distinct decreased thermal stability with respect to the homologous pure sample. Si-substituted hydroxyapatites exhibited higher sintering temperature and increased total shrinkage with respect to pure powders. Nanostructured dense ceramics were obtained by sintering at 1100 deg. C Si-substituted hydroxyapatites derived from Ca(OH) 2

Thomas-Reiche-Khun populations in X-CH 3 and X-C 2H 5 series of molecules

Science.gov (United States)

Zitto, M. E.; Caputo, M. C.; Ferraro, M. B.; Lazzeretti, P.

2000-09-01

Calculations of nuclear electric shieldings, equivalent to dipole moment geometric derivatives, and related to atomic polar tensors, are presented for X-CH 3 and X-C 2H 5 molecules with X=NH 2, OH and F. The electric shielding tensors satisfy a constraint for the electrostatic equilibrium, i.e., the mixed length-acceleration Thomas-Reiche-Khun sum rule, which gives important indications on the reliability of theoretical predictions of IR intensities and leads to the definition of atomic populations. Numerical evidence was found for the additivity and transferability of atomic populations, within the X-substituted alkane series.

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Science.gov (United States)

2010-07-01

... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject to...

Structural requirements for the interaction between class II MHC molecules and peptide antigens

DEFF Research Database (Denmark)

Sette, A; Buus, S; Appella, E

1990-01-01

of binding, it is possible to define certain structural features of peptides that are associated with the capacity to bind to a particular MHC specificity (IA(d) or IE(d)); 3) IA(d) and IE(d) molecules recognize different and independent structures on the antigen molecule; 4) only about 10% of the single...... IA(d) and IE(d) molecules and their peptide ligands, we found that some structural characteristics apply to both antigen-MHC interactions. In particular, we found: 1) each MHC molecule is capable of binding many unrelated peptides through the same peptide-binding site; 2) despite this permissiveness...... amino acid substitutions tested on two IA(d)- and IE(d)-binding peptides had significant effect on their MHC-binding capacities, while over 80% of these substitutions significantly impaired T cell recognition of the Ia-peptide complex; 5) based on the segregation between residues that are crucial for T...

Progesterone radioimmunoassay with the use of progesterone derivative substituted at 12α position

International Nuclear Information System (INIS)

Kula, E.; Stupnicka, R.

1981-01-01

A direct (non-extraction) radioimmunoassay method for progesterone determination in blood plasma has been presented. A new progesterone derivative substituted at 12α position was used as antigen for production of antibody. Cheap and easily accessible substrate -deoxycholic acid - was used as starting material for 9 step degradation procedure yielding 12α-hydroxy-progesterone. The latter compound was subsequently esterified with succinic anhydrine and conjugated with bovine serum albumin. The conjugate was then used for the immunization of rabbits to obtain immune antisera. After the detailed characterization, the obtained antibodies have been used for the determination of progesterone in human and cattle blood plasma. Transcortin present in samples used for the determinations was saturated with the excess of cortisol. The sensitivity of the method was found to be 5 pg in a sample, which corresponds to the concentration of about 0.25 ng/ml in blood plasma, in as much as the volume of plasma used for analysis was 20 ml. The within-series error was 7% when progesterone concentration in plasma samples was higher than 2.5 ng/ml. (author)

Comparison of Inhibitory Activities of meta and para Substituted N-aryl 3-Hydroxypyridin-4-one Mannosides Towards Type 1 Fimbriated E. coli

Directory of Open Access Journals (Sweden)

Vesna Petrović Peroković

2016-06-01

Full Text Available In uropathogenic Escherichia coli, mannose-specific adhesion is mediated by the FimH adhesin located at the tip of type 1 fimbriae. Novel mannosylated N-aryl substituted 3-hydroxypyridin-4ones with meta substituents on the aryl part of the molecule were prepared, and their inhibitory properties towards the adhesion of E. coli to guinea pig erythrocytes explored using the hemagglutination assay. These results were compared with inhibitory potencies of analogous para derivatives. The assays revealed greater preference of FimH towards para substituted compounds in general, with p-nitro and p-methoxy substituted substrates being much more effective then the hydrophobic p-methyl compound. When substituents are in meta position the positive affect on the binding of compounds in the FimH binding site was observed with all compounds tested but the structure with an alkyl group was shown to be the most effective one. This study provides guidelines for the rational design of novel, more effective series of FimH antagonists. This work is licensed under a Creative Commons Attribution 4.0 International License.

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

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Francisco Valdés Zurita

2018-05-01

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

Abscisic-acid-induced cellular apoptosis and differentiation in glioma via the retinoid acid signaling pathway.

Science.gov (United States)

Zhou, Nan; Yao, Yu; Ye, Hongxing; Zhu, Wei; Chen, Liang; Mao, Ying

2016-04-15

Retinoid acid (RA) plays critical roles in regulating differentiation and apoptosis in a variety of cancer cells. Abscisic acid (ABA) and RA are direct derivatives of carotenoids and share structural similarities. Here we proposed that ABA may also play a role in cellular differentiation and apoptosis by sharing a similar signaling pathway with RA that may be involved in glioma pathogenesis. We reported for the first time that the ABA levels were twofold higher in low-grade gliomas compared with high-grade gliomas. In glioma tissues, there was a positive correlation between the ABA levels and the transcription of cellular retinoic acid-binding protein 2 (CRABP2) and a negative correlation between the ABA levels and transcription of fatty acid-binding protein 5 (FABP5). ABA treatment induced a significant increase in the expression of CRABP2 and a decrease in the expression of peroxisome proliferator-activated receptor (PPAR) in glioblastoma cells. Remarkably, both cellular apoptosis and differentiation were increased in the glioblastoma cells after ABA treatment. ABA-induced cellular apoptosis and differentiation were significantly reduced by selectively silencing RAR-α, while RAR-α overexpression exaggerated the ABA-induced effects. These results suggest that ABA may play a role in the pathogenesis of glioma by promoting cellular apoptosis and differentiation through the RA signaling pathway. © 2015 UICC.

Substitution reactions of [Pd(bipy)(malonate)] explored with a ...

Indian Academy of Sciences (India)

−3. NaClO4. Table 1. Metal-Ligand ratios and structures of the product complexes. Metal:Ligand. Ligand. Structure ratio. Product complex. L1 Thioglycolic acid. HS ..... O. Scheme 1. Plausible mechanistic pathway. molecules substitute the bidentate malonate in a consec- utive fashion. Among the three sulphur donor ligands.

Surface tension alteration on calcite, induced by ion substitution

DEFF Research Database (Denmark)

Sakuma, Hiroshi; Andersson, Martin Peter; Bechgaard, Klaus

2014-01-01

The interaction of water and organic molecules with mineral surfaces controls many processes in nature and industry. The thermodynamic property, surface tension, is usually determined from the contact angle between phases, but how does one understand the concept of surface tension at the nanoscale...... preferentially as ion pairs at solution-calcite interfaces. Mg2+ incorporation weakens organic molecule adhesion while strengthening water adsorption so Mg2+ substitution renders calcite more water wet. When Mg2+ replaces 10% of surface Ca2+, the contact angle changes dramatically, by 40 to 70, converting...

Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

OpenAIRE

Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

1993-01-01

The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene d...

Prospecting for novel plant-derived molecules of Rauvolfia serpentina as inhibitors of Aldose Reductase, a potent drug target for diabetes and its complications.

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Shivalika Pathania

Full Text Available Aldose Reductase (AR is implicated in the development of secondary complications of diabetes, providing an interesting target for therapeutic intervention. Extracts of Rauvolfia serpentina, a medicinal plant endemic to the Himalayan mountain range, have been known to be effective in alleviating diabetes and its complications. In this study, we aim to prospect for novel plant-derived inhibitors from R. serpentina and to understand structural basis of their interactions. An extensive library of R. serpentina molecules was compiled and computationally screened for inhibitory action against AR. The stability of complexes, with docked leads, was verified using molecular dynamics simulations. Two structurally distinct plant-derived leads were identified as inhibitors: indobine and indobinine. Further, using these two leads as templates, 16 more leads were identified through ligand-based screening of their structural analogs, from a small molecules database. Thus, we obtained plant-derived indole alkaloids, and their structural analogs, as potential AR inhibitors from a manually curated dataset of R. serpentina molecules. Indole alkaloids reported herein, as a novel structural class unreported hitherto, may provide better insights for designing potential AR inhibitors with improved efficacy and fewer side effects.

Prospecting for novel plant-derived molecules of Rauvolfia serpentina as inhibitors of Aldose Reductase, a potent drug target for diabetes and its complications.

Science.gov (United States)

Pathania, Shivalika; Randhawa, Vinay; Bagler, Ganesh

2013-01-01

Aldose Reductase (AR) is implicated in the development of secondary complications of diabetes, providing an interesting target for therapeutic intervention. Extracts of Rauvolfia serpentina, a medicinal plant endemic to the Himalayan mountain range, have been known to be effective in alleviating diabetes and its complications. In this study, we aim to prospect for novel plant-derived inhibitors from R. serpentina and to understand structural basis of their interactions. An extensive library of R. serpentina molecules was compiled and computationally screened for inhibitory action against AR. The stability of complexes, with docked leads, was verified using molecular dynamics simulations. Two structurally distinct plant-derived leads were identified as inhibitors: indobine and indobinine. Further, using these two leads as templates, 16 more leads were identified through ligand-based screening of their structural analogs, from a small molecules database. Thus, we obtained plant-derived indole alkaloids, and their structural analogs, as potential AR inhibitors from a manually curated dataset of R. serpentina molecules. Indole alkaloids reported herein, as a novel structural class unreported hitherto, may provide better insights for designing potential AR inhibitors with improved efficacy and fewer side effects.

Cation Radical Accelerated Nucleophilic Aromatic Substitution via Organic Photoredox Catalysis.

Science.gov (United States)

Tay, Nicholas E S; Nicewicz, David A

2017-11-15

Nucleophilic aromatic substitution (S N Ar) is a direct method for arene functionalization; however, it can be hampered by low reactivity of arene substrates and their availability. Herein we describe a cation radical-accelerated nucleophilic aromatic substitution using methoxy- and benzyloxy-groups as nucleofuges. In particular, lignin-derived aromatics containing guaiacol and veratrole motifs were competent substrates for functionalization. We also demonstrate an example of site-selective substitutive oxygenation with trifluoroethanol to afford the desired trifluoromethylaryl ether.

Chitosan derivatives with antimicrobial, antitumour and antioxidant activities--a review.

Science.gov (United States)

Jarmila, Vinsová; Vavríková, Eva

2011-01-01

Chitosan is a linear polysaccharide with a good biodegradability, biocompatibility, and no toxicity, which provide it with huge potential for future development. The chitosan molecule appears to be a suitable polymeric complex for many biomedical applications. This review gathers current findings on the antibacterial, antifungal, antitumour and antioxidant activities of chitosan derivatives and concurs with our previous review presenting data collected up to 2008. Antibacterial activity is based on molecular weight, the degree of deacetylation, the type of substitutents, which can be cationic or easily form cations, and the type of bacterium. In general, high molecular weight chitosan cannot pass through cell membranes and forms a film that protects cells against nutrient transport through the microbial cell membrane. Low molecular weight chitosan derivatives are water soluble and can better incorporate the active molecule into the cell. Gram-negative bacteria, often represented by Escherichia coli, have an anionic bacterial surface on which cationic chitosan derivatives interact electrostatically. Thus, many chitosan conjugates have cationic components such as ammonium, pyridinium or piperazinium substituents introduced into their molecules to increase their positive charge. Gram-positive bacteria like Staphylococcus aureus are inhibited by the binding of lower molecular weight chitosan derivatives to DNA or RNA. Chitosan nanoparticles exhibit an increase in loading capacity and efficacy. Antitumour active compounds such as doxorubicin, paclitaxel, docetaxel and norcantharidin are used as drug carriers. It is evident that chitosan, with its low molecular weight, is a useful carrier for molecular drugs requiring targeted delivery. The antioxidant scavenging activity of chitosan has been established by the strong hydrogen-donating ability of chitosan. The low molecular weight and greater degree of quarternization have a positive influence on the antioxidant activity

Cell factory-derived bioactive molecules with polymeric cryogel scaffold enhance the repair of subchondral cartilage defect in rabbits.

Science.gov (United States)

Gupta, Ankur; Bhat, Sumrita; Chaudhari, Bhushan P; Gupta, Kailash C; Tägil, Magnus; Zheng, Ming Hao; Kumar, Ashok; Lidgren, Lars

2017-06-01

We have explored the potential of cell factory-derived bioactive molecules, isolated from conditioned media of primary goat chondrocytes, for the repair of subchondral cartilage defects. Enzyme-linked immunosorbent assay (ELISA) confirms the presence of transforming growth factor-β1 in an isolated protein fraction (12.56 ± 1.15 ng/mg protein fraction). These bioactive molecules were used alone or with chitosan-agarose-gelatin cryogel scaffolds, with and without chondrocytes, to check whether combined approaches further enhance cartilage repair. To evaluate this, an in vivo study was conducted on New Zealand rabbits in which a subchondral defect (4.5 mm wide × 4.5 mm deep) was surgically created. Starting after the operation, bioactive molecules were injected at the defect site at regular intervals of 14 days. Histopathological analysis showed that rabbits treated with bioactive molecules alone had cartilage regeneration after 4 weeks. However, rabbits treated with bioactive molecules along with scaffolds, with or without cells, showed cartilage formation after 3 weeks; 6 weeks after surgery, the cartilage regenerated in rabbits treated with either bioactive molecules alone or in combinations showed morphological similarities to native cartilage. No systemic cytotoxicity or inflammatory response was induced by any of the treatments. Further, ELISA was done to determine systemic toxicity, which showed no difference in concentration of tumour necrosis factor-α in blood serum, before or after surgery. In conclusion, intra-articular injection with bioactive molecules alone may be used for the repair of subchondral cartilage defects, and bioactive molecules along with chondrocyte-seeded scaffolds further enhance the repair. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Facile Synthesis of N -Substituted Benzimidazoles

NARCIS (Netherlands)

Kurhade, Santosh; Rossetti, Arianna; Dömling, Alexander

2016-01-01

A particularly mild and efficient one-pot synthesis of N-substituted benzimidazole derivatives was developed. 2-Fluoro-5-nitrophenylisocyanide reacts with a diverse set of primary amines to afford the respective products in moderate to very good yield (35-95%; 20 examples).

Synthesis of Randomly Substituted Anionic Cyclodextrins in Ball Milling

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László Jicsinszky

2017-03-01

Full Text Available A number of influencing factors mean that the random substitution of cyclodextrins (CD in solution is difficult to reproduce. Reaction assembly in mechanochemistry reduces the number of these factors. However, lack of water can improve the reaction outcomes by minimizing the reagent’s hydrolysis. High-energy ball milling is an efficient, green and simple method for one-step reactions and usually reduces degradation and byproduct formation. Anionic CD derivatives have successfully been synthesized in the solid state, using a planetary ball mill. Comparison with solution reactions, the solvent-free conditions strongly reduced the reagent hydrolysis and resulted in products of higher degree of substitution (DS with more homogeneous DS distribution. The synthesis of anionic CD derivatives can be effectively performed under mechanochemical activation without significant changes to the substitution pattern but the DS distributions were considerably different from the products of solution syntheses.

1-ethyl gallate-2-substituted phenoxymethyl benzimidazoles: synthesis, molecular structure, antimicrobial activities and complex with cr(iii)

International Nuclear Information System (INIS)

Zhao, L.; Wu, J.; Wu, J.; Wang, Z.; Gu, H.

2017-01-01

The design of gallate and benzimidazole containing derivatives is expected to produce new bioactive molecules with multiple applications. Here the synthesis of eight novel benzimidazole compounds containing ethyl gallate and substituted phenoxymethyl units are reported. Firstly, the ring closure reaction between o-phenylendiamine and substituted phenoxyacetic acids resulted in 2-substituted phenoxymethyl benzimidazoles that were then modified by the N-hydroxyethylation with 2-chloroethyl alcohol under a phase transfer catalysis condition. The obtained 1-hydroxyethyl-2-substituted phenoxymethyl benzimidazoles were finally translated into the target title compounds 8a-h by an indirect esterification method in which three O-H groups of gallic acid were first protected by acetyls and deprotected after the esterification reaction by adding hydrazine hydrate. The structures of the title products 8a-h were fully characterized and confirmed by elemental analysis, MS, IR, 1H-NMR, 13C-NMR and single crystal X-ray diffraction techniques. Antimicrobial tests by inhibition zones indicated that these compounds exhibited diverse inhibitory effects against the test bacteria and fungi, and the type and position of the substituent groups in the phenoxymethyl moieties had obvious influence on their antimicrobial activities. Furthermore, the Cr(III) complex of 8h was synthesized, and various spectral, elemental and thermal analysis results confirmed that the central Cr(III) atom coordinated with adjacent hydroxyl groups of two 8h ligands, nitrate and H2O, respectively. (author)

A novel dihydropyridine with 3-aryl meta-hydroxyl substitution blocks L-type calcium channels in rat cardiomyocytes

Energy Technology Data Exchange (ETDEWEB)

Galvis-Pareja, David [Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Zapata-Torres, Gerald [Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago (Chile); Hidalgo, Jorge [Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago (Chile); Ayala, Pedro [Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas and Facultad Medicina, Universidad de Chile, Santiago (Chile); and others

2014-08-15

Rationale: Dihydropyridines are widely used for the treatment of several cardiac diseases due to their blocking activity on L-type Ca{sup 2+} channels and their renowned antioxidant properties. Methods: We synthesized six novel dihydropyridine molecules and performed docking studies on the binding site of the L-type Ca{sup 2+} channel. We used biochemical techniques on isolated adult rat cardiomyocytes to assess the efficacy of these molecules on their Ca{sup 2+} channel-blocking activity and antioxidant properties. The Ca{sup 2+} channel-blocking activity was evaluated by confocal microscopy on fluo-3AM loaded cardiomyocytes, as well as using patch clamp experiments. Antioxidant properties were evaluated by flow cytometry using the ROS sensitive dye 1,2,3 DHR. Results: Our docking studies show that a novel compound with 3-OH substitution inserts into the active binding site of the L-type Ca{sup 2+} channel previously described for nitrendipine. In biochemical assays, the novel meta-OH group in the aryl in C4 showed a high blocking effect on L-type Ca{sup 2+} channel as opposed to para-substituted compounds. In the tests we performed, none of the molecules showed antioxidant properties. Conclusions: Only substitutions in C2, C3 and C5 of the aryl ring render dihydropyridine compounds with the capacity of blocking LTCC. Based on our docking studies, we postulate that the antioxidant activity requires a larger group than the meta-OH substitution in C2, C3 or C5 of the dihydropyridine ring. - Highlights: • Dihydropyridine (DHP) molecules are widely used in cardiovascular disease. • DHPs block Ca{sup 2+} entry through LTCC—some DHPs have antioxidant activity as well. • We synthesized 6 new DHPs and tested their Ca{sup 2+} blocking and antioxidant activities. • 3-Aryl meta-hydroxyl substitution strongly increases their Ca{sup 2+} blocking activity. • 3-Aryl meta-hydroxyl substitution did not affect the antioxidant properties.

Synthesis and characterization of novel substituted N-benzothiazole-2-yl-acetamides

Directory of Open Access Journals (Sweden)

H.C. Sakarya

2016-11-01

Full Text Available Schiff base derivatives of benzothiazole 2a–e have been synthesized by reacting with substituted 2-aminobenzothiazole 1a–e and different substituted benzaldehydes 5a–e. The obtained Schiff bases reaction with NaBH4 has afforded the corresponding some novel amines 3a–e. The condensation of amines with chloroacetylchloride leads to novel amide derivatives 4a–e. The structures of the synthesized compounds are characterized by elemental analysis, IR, MS, 1H NMR and 13C NMR.

Upregulation of miR-150* and miR-630 induces apoptosis in pancreatic cancer cells by targeting IGF-1R.

Directory of Open Access Journals (Sweden)

Lulu Farhana

Full Text Available MicroRNAs have been implicated in many critical cellular processes including apoptosis. We have previously found that apoptosis in pancreatic cancer cells was induced by adamantyl retinoid-related (ARR molecule 3-Cl-AHPC. Here we report that 3-Cl-AHPC-dependent apoptosis involves regulating a number of microRNAs including miR-150* and miR-630. 3-Cl-AHPC stimulated miR-150* expression and caused decreased expression of c-Myb and IGF-1R in the pancreatic cancer cells. 3-Cl-AHPC-mediated reduction of c-Myb resulted in diminished binding of c-Myb with IGF-1R and Bcl-2 promoters, thereby causing repression of their transcription and protein expression. Over-expression of miR-150* also resulted in diminished levels of c-Myb and Bcl-2 proteins. Furthermore, the addition of the miRNA inhibitor 2'-O-methylated miR-150 blocked 3-Cl-AHPC-mediated increase in miR-150* levels and abrogated loss of c-Myb protein. Knockdown of c-Myb in PANC-1 cells resulted in enhanced apoptosis both in the presence or absence of 3-Cl-AHPC confirming the anti-apoptotic property of c-Myb. Overexpression of miR-630 also induced apoptosis in the pancreatic cancer cells and inhibited target protein IGF-1R mRNA and protein expression. Together these results implicate key roles for miR-150* and miR-630 and their targeting of IGF-1R to promote apoptosis in pancreatic cancer cells.

Microwave Assisted Synthesis of N-Arylheterocyclic Substituted-4-aminoquinazoline Derivatives

Directory of Open Access Journals (Sweden)

Ping Lu

2006-04-01

Full Text Available A simple, efficient, and general method has been developed for the synthesis of various N-aryl heterocylic substituted-4-aminoquinazoline compounds from 4-chloro- quinazoline and aryl heterocyclic amines under microwave irradiation using 2-propanol as solvent. The advantages of the use of microwave irradiation in relation to the classical method were demonstrated.

Thermochemical studies on two alkyl-bulky substituted xanthene derivatives: 9,9-dimethylxanthene and 2,7-di-tert-butyl-9,9-dimethylxanthene

International Nuclear Information System (INIS)

Freitas, Vera L.S.; Gomes, José R.B.; Ribeiro da Silva, Maria D.M.C.

2017-01-01

Highlights: • Energetic characterization of two alkyl-bulky substituted xanthene derivatives. • Massic energies of combustion of xanthene derivatives. • Enthalpies of sublimation determined by vacuum drop microcalorimetry technique. • Temperature-vapour pressure dependence by mass-loss Knudsen effusion method. • Gas-phase enthalpies of formation of alkyl xanthene derivatives. - Abstract: Thermodynamic properties of 9,9-dimethylxanthene and 2,7-di-tert-butyl-9,9-dimethylxanthene for the condensed and gas states were derived from experimental and computational studies. Static-bomb combustion calorimetry, vacuum drop microcalorimetry and the Knudsen effusion techniques were used. Computational calculations of the enthalpies of hypothetical reactions in the gaseous phase, using the G3(MP2)//B3LYP composite method, were performed for the two xanthene derivatives. Natural bond orbital (NBO) calculations were also performed to ascertain the structure and reactivity of these compounds. The energetic effects caused by replacing hydrogen atoms in the xanthene moiety by methyl and tert-butyl groups yielding 9,9-dimethylxanthene and 2,7-di-tert-butyl-9,9-dimethylxanthene species were determined from direct comparison of their standard (p o = 0.1 MPa) molar enthalpies of formation in the gaseous phase, at T = 298.15 K.

SYNTHESIS OF SUBSTITUTED FLAVONE DERIVATIVES AS ...

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Flavone (2-phenylchromone) derivatives are naturally occurring heterocyclic compound belongs to the flavanoid group. It showed significant role in pharmaceutical effects [1] including leishmanicidal activity, oviposter stimulant phytoalexins, anti-HIV, vasodilator, antiviral, anti- oxidants, bactericidal, DNA cleavage, ...

Microwave Assisted Synthesis of 2,2'-Arylene-substituted Bis(4H-3,1-Benzoxazin-4-one Derivatives Using the Complex Cyanuric Chloride/N,N-Dimethylformamide

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Mehdi Shariat

2012-09-01

Full Text Available A new and efficient method has been designed to prepare 2,2'-arylene-substituted bis(4H-3,1-benzoxazin-4-one derivatives by using the mixture of cyanuric chloride and N,N-dimethylformamide in a microwave-assisted reaction. The method used and presented here has good rate enhancement and excellent yields.

Catalytic hydrodeoxygenation of methyl-substituted phenols: correlations of kinetic parameters with molecular properties.

Science.gov (United States)

Massoth, F E; Politzer, P; Concha, M C; Murray, J S; Jakowski, J; Simons, Jack

2006-07-27

The hydrodeoxygenation of methyl-substituted phenols was carried out in a flow microreactor at 300 degrees C and 2.85 MPa hydrogen pressure over a sulfided CoMo/Al(2)O(3) catalyst. The primary reaction products were methyl-substituted benzene, cyclohexene, cyclohexane, and H(2)O. Analysis of the results suggests that two independent reaction paths are operative, one leading to aromatics and the other to partially or completely hydrogenated cyclohexanes. The reaction data were analyzed using Langmuir-Hinshelwood kinetics to extract the values of the reactant-to-catalyst adsorption constant and of the rate constants characterizing the two reaction paths. The adsorption constant was found to be the same for both reactions, suggesting that a single catalytic site center is operative in both reactions. Ab initio electronic structure calculations were used to evaluate the electrostatic potentials and valence orbital ionization potentials for all of the substituted phenol reactants. Correlations were observed between (a) the adsorption constant and the two reaction rate constants measured for various methyl-substitutions and (b) certain moments of the electrostatic potentials and certain orbitals' ionization potentials of the isolated phenol molecules. On the basis of these correlations to intrinsic reactant-molecule properties, a reaction mechanism is proposed for each pathway, and it is suggested that the dependencies of adsorption and reaction rates upon methyl-group substitution are a result of the substituents' effects on the electrostatic potential and orbitals rather than geometric (steric) effects.

The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis.

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Fairfield, Heather; Falank, Carolyne; Harris, Elizabeth; Demambro, Victoria; McDonald, Michelle; Pettitt, Jessica A; Mohanty, Sindhu T; Croucher, Peter; Kramer, Ina; Kneissel, Michaela; Rosen, Clifford J; Reagan, Michaela R

2018-02-01

The bone marrow niche is a dynamic and complex microenvironment that can both regulate, and be regulated by the bone matrix. Within the bone marrow (BM), mesenchymal stromal cell (MSC) precursors reside in a multi-potent state and retain the capacity to differentiate down osteoblastic, adipogenic, or chondrogenic lineages in response to numerous biochemical cues. These signals can be altered in various pathological states including, but not limited to, osteoporotic-induced fracture, systemic adiposity, and the presence of bone-homing cancers. Herein we provide evidence that signals from the bone matrix (osteocytes) determine marrow adiposity by regulating adipogenesis in the bone marrow. Specifically, we found that physiologically relevant levels of Sclerostin (SOST), which is a Wnt-inhibitory molecule secreted from bone matrix-embedded osteocytes, can induce adipogenesis in 3T3-L1 cells, mouse ear- and BM-derived MSCs, and human BM-derived MSCs. We demonstrate that the mechanism of SOST induction of adipogenesis is through inhibition of Wnt signaling in pre-adipocytes. We also demonstrate that a decrease of sclerostin in vivo, via both genetic and pharmaceutical methods, significantly decreases bone marrow adipose tissue (BMAT) formation. Overall, this work demonstrates a direct role for SOST in regulating fate determination of BM-adipocyte progenitors. This provides a novel mechanism for which BMAT is governed by the local bone microenvironment, which may prove relevant in the pathogenesis of certain diseases involving marrow adipose. Importantly, with anti-sclerostin therapy at the forefront of osteoporosis treatment and a greater recognition of the role of BMAT in disease, these data are likely to have important clinical implications. © 2017 Wiley Periodicals, Inc.

Peculiar properties of photoinduced hydroxylaminolysis in different bacteriorhodopsin-based media using O-substituted hydroxylamines.

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Dyukova, Tatyana V; Druzhko, Anna B

2010-01-01

The process of photoinduced hydroxylaminolysis has been re-examined in different bacteriorhodopsin (BR)-based media using O-substituted hydroxylamines, in particular, O-(4-nitrobenzyl) hydroxylamine hydrochloride (NBHA), O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine hydrochloride (FBHA) and O-(t-butyl) hydroxylamine hydrochloride (BHA). Both wild type (WT) and D96N BR-based gelatine films and gels were studied. The expected increase in the bleaching rate of BR in gelatin films by using O-substituted hydroxylamines in place of HA was not achieved. On the other hand, it was shown that in gels HA derivatives NBHA and FBHA (as against HA itself) do provide about three- to four-fold higher bleaching rate. By contrast to that in films, D96N BR in gels demonstrates more effective bleaching as compared to WT BR. The plausible interpretation for the results is discussed in frames of reduced mobilities of large-sized molecules of O-substituted hydroxylamines in dehydrated media. FBHA- or NBHA-modified gels possess higher photosensitivity both with D96N and WT BR (as compared with that for HA-modified gels) and offer a potentiality for application as an irreversible-recording medium. As anticipated, it is specifically D96N BR gel modified with FBHA that may present a promising medium suitable for write-once recording thus extending the range of recording materials in the optical processing field. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

[Anti-arrhythmic action of some amidinohydrazone substituted benzophenones. 1. Synthesis of new amidinohydrazone and N-phenylamidinohydrazone substituted benzophenones].

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Richter, P H; Kasbohm, K; Besch, A; Hagen, A

1992-10-01

The title compounds are synthesized as a rule by condensation of substituted benzophenones and derivatives of aminoguanidine in the presence of up to 2.5 moles of an anorganic acid. They can be obtained alternatively via corresponding hydrazones, thiosemicarbazones or methylthiothiocarbonylhydrazones.

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

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Andreas Gansäuer

2013-08-01

Full Text Available The intramolecular radical addition to aniline derivatives was investigated by DFT calculations. The computational methods were benchmarked by comparing the calculated values of the rate constant for the 5-exo cyclization of the hexenyl radical with the experimental values. The dispersion-corrected PW6B95-D3 functional provided very good results with deviations for the free activation barrier compared to the experimental values of only about 0.5 kcal mol−1 and was therefore employed in further calculations. Corrections for intramolecular London dispersion and solvation effects in the quantum chemical treatment are essential to obtain consistent and accurate theoretical data. For the investigated radical addition reaction it turned out that the polarity of the molecules is important and that a combination of electrophilic radicals with preferably nucleophilic arenes results in the highest rate constants. This is opposite to the Minisci reaction where the radical acts as nucleophile and the arene as electrophile. The substitution at the N-atom of the aniline is crucial. Methyl substitution leads to slower addition than phenyl substitution. Carbamates as substituents are suitable only when the radical center is not too electrophilic. No correlations between free reaction barriers and energies (ΔG‡ and ΔGR are found. Addition reactions leading to indanes or dihydrobenzofurans are too slow to be useful synthetically.

Study of antineoplastic action of novel isomeric derivatives of 4-thiazolidinone

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М. R. Fil

2014-12-01

Full Text Available Pyrazole- and aryl-substituted derivatives of 4-thiazolidinone belong to a perspective group of compounds with potential antitumor action. Earlier, we have demonstrated high toxicity in vitro of several 4-thiazolidinones derivatives towards tumor cell lines. To further enhance the antitumor activity of novel 4-thiazolidinones, their chemical scaffold was optimized, and new pyrazole-thiazolidinones were synthesized. That allowed us to combine in one molecule the potential pharmacophore centres of previously tested compounds. As a result, “hybrid” 4-thiazolidinones exhibit higher toxicity in vitro toward tumor cells of various origin. The molecular mechanisms of antineoplastic activity of these compounds and intensity of induction of apoptosis strongly depended on the position of the substituent in the thiazolidinone cycle. In particular, Les-3661 compound, containing pyrazoline fragment in the 4th position of thiazolidinone core, exhibits 14 times higher cytotoxic activity towards tumor cells (LC50 = 3 µM in comparison to its 2-substituted isomer Les-3713 (LC50 = 42 µM. It is demonstrated that in terms of underlying molecular mechanisms for cytotoxic effect the Les-3661 compound induced caspase-8 and caspase-9 dependent mixed-type of apoptosis, while Les-3713 induced apoptosis mediated only by the caspase-8.

2D QSAR studies of the inhibitory activity of a series of substituted purine derivatives against c-Src tyrosine kinase

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Mukesh C. Sharma

2016-07-01

Full Text Available A series of 34 substituted purine analogues derivatives were subjected to quantitative structure-activity relationship analyses as inhibitors of c-Src tyrosine kinase. Partial least squares regression was applied to derive QSAR models, which were further validated for statistical significance by internal and external validation. The best QSAR model developed had a good predictive correlation coefficient (r2 of 0.8319, a significant cross-validated correlation coefficient (q2 of 0.7550, and an r2 for the external test set (pred_r2 of 0.7983. It was developed from the PLS method with descriptors including the SsCH3E-index, H-Donor Count, T_2_Cl_3, and negative correlation with SsOHcount. The current study provides better insight into the future design of more potent c-Src tyrosine kinase inhibitors prior to synthesis.

Influence of methoxy- and nitro-substitutions in the aromatic ring on proton donation ability in hydrogen bond and on the amino group parameters of free and H-bonded molecules of 2-aminopyrimidine

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Borisenko, V. E.; Krekov, S. A.; Fomenko, M. Yu.; Koll, A.; Lipkovski, P.

2008-06-01

Amino- and imino- forms of pyrimidine are widely presented as part of antibiotics, corrective medications for heart failures and metabolic stimulators. Hydrogen bonding is one of the fundamental interactions between biologically active molecules. This type of interactions provides flexibility, speed and variety of the biochemical processes. Proton donation properties of aminopyrimidines significantly depend on the position, number and kind of the substituent in its aromatic ring. In present work we studied the influence of the methoxy- and nitro-substitutions in the phenyl radical of pyridine and pyrimidine cycles on the proton donation ability of the amino group in hydrogen bonds as well as on its geometrical, force, electro-optical and thermodynamical characteristics in free and H-bonded (1:1 and 1:2, with various proton acceptors) molecules of primary aromatic amines. Acetonitrile, dioxane, tetrahydrofourane, dimethylformamide, dimethylsulfoxide and hexamethylphosphoramide (whose proton accepting properties vary within a wide range) were used as proton acceptors in our research. In the region of the amino group stretching and deformation vibrations the IR spectra of free and H-bonded (1:1) molecules of 2-amino-4,6-dimethoxy- and 2-amino-5-nitropyrimidine were studied in complexes with proton acceptors in CCl 4 within the temperature range 288-328 K. The spectra of 1:2 complexes were studied in undiluted aprotic solvents. The following spectral characteristics of absorption bands in amino group stretching vibrations were determined: M(0) (zero spectral moment, integrated intensity B); M(1) (first spectral moment, band "centre of gravity"); effective half width, related to the second central moment (Δ ν1/2) eff = 2( M(2)) 1/2, frequencies of the deformation vibrations δ(HNH) of free and H-bonded molecules. It was shown that changes of the absorption band spectral characteristics of the amino group stretching and deformation vibrations in the analyzed

A comparison of carotenoids, retinoids, and tocopherols in the serum and buccal mucosa of chronic cigarette smokers versus nonsmokers.

OpenAIRE

Gabriel, Helen E.; Liu, Zhenhua; Crott, Jimmy W.; Choi, Sang-Woon; Song, Byeng Chun; Mason, Joel B.; Johnson, Elizabeth J.

2006-01-01

Biomarker: micronucleiDiet, food or substance: carotenoids, retinoids, and tocopherols. Study type: humans Study design: case-control studyStudy size: 35 smokers and 21 nonsmokers Tissue/biological material/sample size: Buccal Mucosa Cells (BMC); blood. Method of analysis: freshly prepared BMC suspension were smeared on a microscope slide and scored for the presence of micronuclei. Impact on outcome (including dose-response): General linear regression with adjustments for dietary intake showe...

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules

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Christian Hundshammer

2018-02-01

Full Text Available pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. However, most of the known HP-sensors have only individually and not comprehensively been analyzed for their biocompatibility, their pH sensitivity under physiological conditions, and the effects of chemical derivatization on their logarithmic acid dissociation constant (pKa. Proteinogenic amino acids are biocompatible, can be hyperpolarized and have at least two pH sensitive moieties. However, they do not exhibit a pH sensitivity in the physiologically relevant pH range. Here, we developed a systematic approach to tailor the pKa of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, we identified several derivatives such as [1-13C]serine amide and [1-13C]-2,3-diaminopropionic acid as novel pH sensors. They bear several spin-1/2 nuclei (13C, 15N, 31P with high sensitivity up to 4.8 ppm/pH and we show that 13C spins can be hyperpolarized with dissolution dynamic polarization (DNP. Our findings elucidate the molecular mechanisms of chemical shift pH sensors that might help to design tailored probes for specific pH in vivo imaging applications.

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules.

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Hundshammer, Christian; Düwel, Stephan; Ruseckas, David; Topping, Geoffrey; Dzien, Piotr; Müller, Christoph; Feuerecker, Benedikt; Hövener, Jan B; Haase, Axel; Schwaiger, Markus; Glaser, Steffen J; Schilling, Franz

2018-02-15

pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP) magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. However, most of the known HP-sensors have only individually and not comprehensively been analyzed for their biocompatibility, their pH sensitivity under physiological conditions, and the effects of chemical derivatization on their logarithmic acid dissociation constant (p K a ). Proteinogenic amino acids are biocompatible, can be hyperpolarized and have at least two pH sensitive moieties. However, they do not exhibit a pH sensitivity in the physiologically relevant pH range. Here, we developed a systematic approach to tailor the p K a of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, we identified several derivatives such as [1- 13 C]serine amide and [1- 13 C]-2,3-diaminopropionic acid as novel pH sensors. They bear several spin-1/2 nuclei ( 13 C, 15 N, 31 P) with high sensitivity up to 4.8 ppm/pH and we show that 13 C spins can be hyperpolarized with dissolution dynamic polarization (DNP). Our findings elucidate the molecular mechanisms of chemical shift pH sensors that might help to design tailored probes for specific pH in vivo imaging applications.

Influence of substitution on the optical properties of functionalized pentacene monomers and crystals: Experiment and theory

KAUST Repository

Saeed, Yasir

2013-10-01

The influence of solubilizing substitutional groups on the electronic structure of prototypical functionalized pentacene molecules and crystals is studied by a combined experimental and theoretical approach. We experimentally establish characteristic effects of substituents on the electronic structure and relate those to theoretical optical spectra in order to explain the experimental results and provide a comprehensive picture of the substitution effects. Bands associated to C/Si atoms connecting the functional side group to the pentacene in the (6,13)-positions are the main contributors to the optical transitions. The amplitude of the redshift between the crystals and molecules provides insight in the packing structure. © 2013 Elsevier B.V. All rights reserved.

The elasticity of substitution of superlative price indices

OpenAIRE

Petter Frenger

2005-01-01

Abstract: The paper presents a method for computing the curvature implicit in the use of superlative price indices. It extends the quadratic lemma and allows us to compute the elasticity of substitution of the underlying preferences in the direction of the observed price change for the Törnqvist and the quadratic mean of order r indices. It derives the expressions for the directional shadow elasticity of substitution and applies the results to the Norwegian CPI data base. Ke...

Novel 5-Fluorouracil Derivatives: Synthesis and Cytotoxic Activity of 2-Butoxy-4-Substituted 5-Fluoropyrimidines

International Nuclear Information System (INIS)

Sun, Jian; Zhou, Wei; Hu, Weixiao; Shan, Shang; Zhang, Shijie; Li, Haibo

2013-01-01

Twenty two new 5-fluorouracil (5-FU) derivatives, 2-butoxy-4-substituted 5-fluoropyrimidines, were synthesized and characterized by IR, 1 H NMR, MS, HRMS. All compounds were preliminarily evaluated by MTT assay on human liver BEL-7402 cancer cell line in vitro. Ten compounds were selected to test their cytotoxic activity against A549, HL-60 and MCF-7 cancer cell lines in vitro. These compounds were more sensitive to BEL-7402 than other cell lines, particularly, cytotoxic activity of compounds 6b, 6d-f, 6p, 6s-u were in sub-micromolar scale. The highest cytotoxic potency against A549, HL-60 and MCF-7 was shown by 2-butoxy-4-chloro-5-fluoropyrimidine (5) with IC 50 values of 0.10, 1.66 and 0.59 μM, respectively. Compounds 6d and 6e were effective against MCF-7 with IC 50 9.73 μM and HL-60 with IC 50 8.83 μM, respectively

Halogeno-substituted 2-aminobenzoic acid derivatives for negative ion fragmentation studies of N-linked carbohydrates.

Science.gov (United States)

Harvey, David J

2005-01-01

Negative ion electrospray mass spectra of high-mannose N-linked glycans derivatised with 2-aminobenzoic acids and ionised from solutions containing ammonium hydroxide gave prominent [M-H](-) ions accompanied by weaker [M-2H](2-) ions. Fragmentation of both types of ions gave prominent singly charged glycosidic cleavage ions containing the derivatised reducing terminus and ions from the non-reducing terminus that appeared to be products of cross-ring cleavages. Differentiation of these two groups of ions was conveniently achieved in a single spectrum by use of chloro- or bromo-substituted benzoic acids in order to label ions containing the derivative with an atom with a distinctive isotope pattern. Fragmentation of the doubly charged ions gave more abundant fragments, both singly and doubly charged, than did fragmentation of the singly charged ions, but information of chain branching was masked by the appearance of prominent ions produced by internal cleavages. Copyright (c) 2005 John Wiley & Sons, Ltd.

Structure-activity relationships for novel drug precursor N-substituted-6-acylbenzothiazolon derivatives: A theoretical approach

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Sıdır, Yadigar Gülseven; Sıdır, İsa

2013-08-01

In this study, the twelve new modeled N-substituted-6-acylbenzothiazolon derivatives having analgesic analog structure have been investigated by quantum chemical methods using a lot of electronic parameters and structure-activity properties; such as molecular polarizability (α), dipole moment (μ), EHOMO, ELUMO, q-, qH+, molecular volume (Vm), ionization potential (IP), electron affinity (EA), electronegativity (χ), molecular hardness (η), molecular softness (S), electrophilic index (ω), heat of formation (HOF), molar refractivity (MR), octanol-water partition coefficient (log P), thermochemical properties (entropy (S), capacity of heat (Cv)); as to investigate activity relationships with molecular structure. The correlations of log P with Vm, MR, ω, EA, EHOMO - ELUMO (ΔE), HOF in aqueous phase, χ, μ, S, η parameters, respectively are obtained, while the linear relation of log P with IP, Cv, HOF in gas phase are not observed. The log P parameter is obtained to be depending on different properties of compounds due to their complexity.

Synthesis and in vitro cytotoxicity of novel C-12 substituted-14-deoxy-andrographolide derivatives as potent anti-cancer agents.

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Kandanur, Sai Giridhar Sarma; Golakoti, Nageswara Rao; Nanduri, Srinivas

2015-12-15

Andrographolide, the major labdane diterpenoid from Andrographis paniculata has been reported to be cytotoxic against various cancer cells in vitro. Our research efforts led to the discovery of novel 12-phenyl thio and 12-aryl amino-14-deoxy-andrographolide derivatives (III q and III r) with potent cytotoxic activity, 12-benzyl amino-14-deoxy-andrographolide analogues showing broad range of cytotoxic activity against most of the cell lines and 12-alkyl amino-14-deoxy-andrographolide derivatives being selective to few cell lines (PC-3 and HOP-92), when the selected analogues were evaluated against 60 human cancer cell line panel at National Cancer Institute (N.C.I.), USA. The SAR (structure activity relationship) studies demonstrated potent activity for the compounds containing the following functionalities at C-12: substituted aryl amino/phenyl thio>benzylamine>alkyl amine. The significant cytotoxic activity observed for compounds III q and III r suggest that these could serve as templates for further optimization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Theoretical study of structure and electronic properties of cyano-substituted pyrroles

International Nuclear Information System (INIS)

Rimarcik, Jan; Lukes, Vladimir; Klein, Erik; Griesser, Markus; Kelterer, Anne-Marie

2008-01-01

DFT and ab initio MP2 calculations of optimal geometries, dipole moments, polarizabilities, excitation energies and enthalpies of hydrogen or proton transfer from N-H group for cyano derivatives of pyrrole are presented. CN groups in α and β positions have distinct effects on electron spectra absorption bands. CN in α position causes larger bathochromic shift in comparison to β position. N-H bond dissociation enthalpies (BDE) of substituted pyrroles are higher by 7 kJ mol -1 than pyrrole BDE. Number and position of CN groups do not affect BDEs. Proton affinities of pyrrolyl anions and enthalpies of electron transfer from these anions are proportional to the number of CN groups in molecule. Each CN group causes decrease in proton affinity by 72 kJ mol -1 and 73 kJ mol -1 rise in electron transfer enthalpy. For several studied pyrroles, BDEs, proton affinities and electron transfer enthalpies in water and benzene were computed

Buthalital and methitural – 5,5-substituted derivatives of 2-thiobarbituric acid forming the same type of hydrogen-bonded chain

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Thomas Gelbrich

2017-12-01

Full Text Available The molecule of buthalital, (I [systematic name: 5-(2-methylpropyl-5-(prop-2-en-1-yl-2-sulfanylidene-1,3-diazinane-4,6-dione], C11H16N2O2S, exhibits a planar pyrimidine ring, whereas the pyrimidine ring of methitural, (II [systematic name: 5-(1-methylbutyl-5-[2-(methylsulfanylethyl]-2-sulfanylidene-1,3-diazinane-4,6-dione], C12H20N2O2S2, is slightly puckered. (I and (II contain the same hydrogen-bonded chain structure in which each molecule is connected, via four N—H...O=C hydrogen bonds, to two other molecules, resulting in a hydrogen-bonded chain displaying a sequence of R22(8 rings. The same type of N—H...O=C hydrogen-bonded chain has previously been found in several 5,5-disubstituted derivatives of barbituric acid which are chemically closely related to (I and (II.

Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina.

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Aurélie Cubizolle

Full Text Available In retinal pigment epithelium (RPE, RPE65 catalyzes the isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol in the visual cycle and controls the rhodopsin regeneration rate. However, the mechanisms by which these processes are regulated are still unclear. Fatty Acid Transport Protein 1 (FATP1 is involved in fatty acid uptake and lipid metabolism in a variety of cell types. FATP1 co-localizes with RPE65 in RPE and inhibits its isomerase activity in vitro. Here, we further investigated the role of FATP1 in the visual cycle using transgenic mice that overexpress human FATP1 specifically in the RPE (hFATP1TG mice. The mice displayed no delay in the kinetics of regeneration of the visual chromophore 11-cis-retinal after photobleaching and had no defects in light sensitivity. However, the total retinoid content was higher in the hFATP1TG mice than in wild type mice, and the transgenic mice also displayed an age-related accumulation (up to 40% of all-trans-retinal and retinyl esters that was not observed in control mice. Consistent with these results, hFATP1TG mice were more susceptible to light-induced photoreceptor degeneration. hFATP1 overexpression also induced an ~3.5-fold increase in retinosome autofluorescence, as measured by two-photon microscopy. Interestingly, hFATP1TG retina contained ~25% more photoreceptor cells and ~35% longer outer segments than wild type mice, revealing a non-cell-autonomous effect of hFATP1 expressed in the RPE. These data are the first to show that FATP1-mediated fatty acid uptake in the RPE controls both retinoid metabolism in the outer retina and photoreceptor development.

Systematic studies of molecular vibrational anharmonicity and vibration-rotation interaction by self-consistent-field higher derivative methods: Applications to asymmetric and symmetric top and linear polyatomic molecules

International Nuclear Information System (INIS)

Clabo, D.A. Jr.

1987-04-01

Inclusion of the anharmonicity normal mode vibrations [i.e., the third and fourth (and higher) derivatives of a molecular Born-Oppenheimer potential energy surface] is necessary in order to theoretically reproduce experimental fundamental vibrational frequencies of a molecule. Although ab initio determinations of harmonic vibrational frequencies may give errors of only a few percent by the inclusion of electron correlation within a large basis set for small molecules, in general, molecular fundamental vibrational frequencies are more often available from high resolution vibration-rotation spectra. Recently developed analytic third derivatives methods for self-consistent-field (SCF) wavefunctions have made it possible to examine with previously unavailable accuracy and computational efficiency the anharmonic force fields of small molecules

Systematic studies of molecular vibrational anharmonicity and vibration-rotation interaction by self-consistent-field higher derivative methods: Applications to asymmetric and symmetric top and linear polyatomic molecules

Energy Technology Data Exchange (ETDEWEB)

Clabo, D.A. Jr.

1987-04-01

Inclusion of the anharmonicity normal mode vibrations (i.e., the third and fourth (and higher) derivatives of a molecular Born-Oppenheimer potential energy surface) is necessary in order to theoretically reproduce experimental fundamental vibrational frequencies of a molecule. Although ab initio determinations of harmonic vibrational frequencies may give errors of only a few percent by the inclusion of electron correlation within a large basis set for small molecules, in general, molecular fundamental vibrational frequencies are more often available from high resolution vibration-rotation spectra. Recently developed analytic third derivatives methods for self-consistent-field (SCF) wavefunctions have made it possible to examine with previously unavailable accuracy and computational efficiency the anharmonic force fields of small molecules.

Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors

Science.gov (United States)

Giner, Xavier C; Cotnoir-White, David; Mader, Sylvie; Lévesque, Daniel

2017-01-01

Retinoid X receptors (RXR) play a role as master regulators due to their capacity to form heterodimers with other nuclear receptors. Accordingly, retinoid signaling is involved in multiple biological processes, including development, cell differentiation, metabolism and cell death. However, the role and functions of RXR in different heterodimer complexes remain unsolved, mainly because most RXR drugs (called rexinoids) are not selective to specific heterodimer complexes. This also strongly limits the use of rexinoids for specific therapeutic approaches. In order to better characterize rexinoids at specific nuclear receptor complexes, we have developed and optimized luciferase protein complementation-based Bioluminescence Resonance Energy Transfer (BRET) assays, which can directly measure recruitment of a co-activator motif fused to yellow fluorescent protein (YFP) by specific nuclear receptor dimers. To validate the assays, we compared rexinoid modulation of co-activator recruitment by RXR homodimer, and heterodimers Nur77/RXR and Nurr1/RXR. Results reveal that some rexinoids display selective co-activator recruitment activities with homo- or hetero-dimer complexes. In particular, SR11237 (BMS649) has increased potency for recruitment of co-activator motif and transcriptional activity with the Nur77/RXR heterodimer compared to other complexes. This technology should prove useful to identify new compounds with specificity for individual dimeric species formed by nuclear receptors. PMID:26148973

Effect of deuteration on the vibrational spectra of organic molecules

International Nuclear Information System (INIS)

Billes, Ferenc; Endredi, Henrietta; Varady, Balazs

2001-01-01

The stable isotope substitution of organic compounds deforms their vibrational spectra. The modifications of the spectra appear as band shifts and changes in intensities and shapes of the bands. The magnitude of the effect depends on the ratio of the masses of the new and old isotopes and on the atom active position. According to these mentioned reasons large effects can be observed only if hydrogen atoms are substituted. With the effect of the substitution we dealt already in a former lecture. In this lecture we concentrate on the effect of the change of hydrogen to deuterium. We investigate the changes both experimentally and theoretically. There are two possibilities: - the hydrogen atom is in an active position, its interaction with the environment is strong, either it can dissociate or move on the skeleton of the molecule (tautomerism, resonance) and it can build hydrogen bond, (e.g. it is connected to nitrogen and oxygen atoms); - the hydrogen atom is in an indifferent position in the molecule, its interaction with the environment is weak (e.g. it joins carbon atom). When building the hydrogen bond besides the hydrogen donors also acceptors exist, namely, oxygen and nitrogen atoms having non-bonded electron pairs. When comparing the experimental and theoretical (calculated) effects of this type of isotope changes one must take into account that the calculations refer to the isolated molecule while the experimental spectra characterize the compound. The hydrogen bond is a very strong intermolecular interaction and produces tremendous changes in the infrared spectrum of the molecule in comparison to the imagined theoretical spectrum of the molecule. Some bands disappear, appear, or shift and deform drastically. The H/D change diminishes these effects. Of course, these changes entail the shift of several bands. The Raman spectrum is less sensitive to the large dipole moment changes therefore the deuteration effect is there less dramatic. Deuteration of hydrogen

Calculation of gamma spectra for positron annihilation on molecules

Energy Technology Data Exchange (ETDEWEB)

Green, Dermot G; Gribakin, G F [Centre for Theoretical Atomic, Molecular and Optical Physics, Queen' s University Belfast, BT7 1NN (United Kingdom); Wang, F [Centre for Molecular Simulation, Sinburne University of Technology, Melbourne, Victoria 3122 (Australia); Surko, C M, E-mail: dgreen09@qub.ac.u [Physics Department, University of California, San Diego, La Jolla, California 92093-0319 (United States)

2009-11-01

Gamma spectra for positron annihilation on molecules are calculated based on molecular electron momentum densities and using an atomic adjustment factor that accounts for the positron. Results for H{sub 2} agree well with experiment. Analysis of methane and larger alkanes and their substitutes is underway.

The discovery of new potent non-peptide Angiotensin II AT1 receptor blockers: A concise synthesis, molecular docking studies and biological evaluation of N-substituted 5-butylimidazole derivatives

Czech Academy of Sciences Publication Activity Database

Agelis, G.; Resvani, A.; Durdagi, S.; Spyridaki, K.; Tůmová, Tereza; Slaninová, Jiřina; Giannopoulos, P.; Vlahakos, D.; Liapakis, G.; Mavromoustakos, T.; Matsoukas, J.

2012-01-01

Roč. 55, Sep (2012), s. 358-374 ISSN 0223-5234 Institutional research plan: CEZ:AV0Z40550506 Keywords : synthesis * angiotensin II receptor blockers * N-substituted 5-butylimidazole derivatives * antihypertensive activity * molecular docking Subject RIV: CC - Organic Chemistry Impact factor: 3.499, year: 2012

/sup 13/C-/sup 13/C spin-spin coupling in structural investigations. VII. Substitution effects and direct carbon-carbon constants of the triple bond in acetyline derivatives

Energy Technology Data Exchange (ETDEWEB)

Krivdin, L.B.; Proidakov, A.G.; Bazhenov, B.N.; Zinchenko, S.V.; Kalabin, G.A.

1989-01-10

The effects of substitution on the direct /sup 13/C-/sup 13/C spin-spin coupling constants of the triple bond were studied in 100 derivatives of acetylene. It was established that these parameters exhibit increased sensitivity to the effect of substituents compared with other types of compounds. The main factor which determines their variation is the electronegativity of the substituting groups, and in individual cases the /pi/-electronic effects are appreciable. The effect of the substituents with an element of the silicon subgroup at the /alpha/ position simultaneously at the triple bond or substituent of the above-mentioned type and a halogen atom.

Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

Science.gov (United States)

Nishimura, R; Li, W; Kashishian, A; Mondino, A; Zhou, M; Cooper, J; Schlessinger, J

1993-11-01

Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth factors stimulate the phosphorylation of Nck and its association with autophosphorylated growth factor receptors. A panel of platelet-derived growth factor (PDGF) receptor mutations at tyrosine residues has been used to identify the Nck binding site. Here we show that mutation at Tyr-751 of the PDGF beta-receptor eliminates Nck binding both in vitro and in living cells. Moreover, the Y751F PDGF receptor mutant failed to mediate PDGF-stimulated phosphorylation of Nck in intact cells. A phosphorylated Tyr-751 is also required for binding of phosphatidylinositol-3 kinase to the PDGF receptor. Hence, the SH2 domains of p85 and Nck share a binding site in the PDGF receptor. Competition experiments with different phosphopeptides derived from the PDGF receptor suggest that binding of Nck and p85 is influenced by different residues around Tyr-751. Thus, a single tyrosine autophosphorylation site is able to link the PDGF receptor to two distinct SH2 domain-containing signaling molecules.

Diaminoethane adsorption and water substitution on hydrated TiO2: a thermochemical study based on first-principles calculations.

Science.gov (United States)

Hémeryck, Anne; Motta, Alessandro; Swiatowska, Jolanta; Pereira-Nabais, Catarina; Marcus, Philippe; Costa, Dominique

2013-07-14

Epoxy-amines are used as structural adhesives deposited on Ti. The amine adhesion to a Ti surface depends highly on the surface state (oxidation, hydroxylation). Amines may adsorb above preadsorbed water molecules or substitute them to bind directly to surface Ti(4+) Lewis acid sites. The adsorption of a model amine molecule, diaminoethane (DAE), on a model surface, hydrated TiO2-anatase (101) surface, is investigated using Density Functional Theory including Dispersive forces (DFT-D) calculations. DAE adsorption and water substitution by DAE are exothermic processes and turn nearly isoenergetic at high coverage with adsorption-substitution energies around -0.3 eV (including dispersion forces and ZPE). Complementary ab initio molecular dynamics studies also suggest that the formation of an amine-water interaction induces water desorption from the surface at room temperature, a preliminary step towards the amine-Ti bond formation. An atomistic thermodynamic approach is developed to evaluate the interfacial free energy balance of both processes (adsorption and substitution). The main contributions to the energetic balance are dispersive interactions between molecules and the surface on the exergonic side, translational and rotational entropic contributions on the endergonic one. The substitution process is stabilized by 0.55 eV versus the adsorption one when free solvation, rotational and vibrational energies are considered. The main contribution to this free energy gain is due to water solvation. The calculations suggest that in toluene solvent with a water concentration of 10(-4) M or less, a full DAE layer replaces a preadsorbed water layer for a threshold concentration of DAE ≥ 0.1 M.

Induction of discrete apoptotic pathways by bromo-substituted indirubin derivatives in invasive breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Nicolaou, Katerina A. [Department of Biological Sciences, University of Cyprus, Nicosia (Cyprus); Liapis, Vasilis; Evdokiou, Andreas [Department of Surgery, Basil Hetzel Institute, Adelaide University, Adelaide (Australia); Constantinou, Constantina [St. George' s University of London Medical School at the University of Nicosia, Nicosia (Cyprus); Magiatis, Prokopios; Skaltsounis, Alex L. [Faculty of Pharmacy, University of Athens, Athens (Greece); Koumas, Laura; Costeas, Paul A. [Center for Study of Hematological Malignancies, Nicosia (Cyprus); Constantinou, Andreas I., E-mail: andreasc@ucy.ac.cy [Department of Biological Sciences, University of Cyprus, Nicosia (Cyprus)

2012-08-17

Highlights: Black-Right-Pointing-Pointer The effects of 6BIO and 7BIO are evaluated against five breast cancer cell lines. Black-Right-Pointing-Pointer 6BIO induces a caspase dependent apoptotic effect via the intrinsic pathway. Black-Right-Pointing-Pointer 7BIO promotes G{sub 2}/M cells cycle arrest. Black-Right-Pointing-Pointer 7BIO triggers a caspase-8 mediated apoptotic pathway. Black-Right-Pointing-Pointer 7BIO triggers and a caspase independent pathway. -- Abstract: Indirubin derivatives gained interest in recent years for their anticancer and antimetastatic properties. The objective of the present study was to evaluate and compare the anticancer properties of the two novel bromo-substituted derivatives 6-bromoindirubin-3 Prime -oxime (6BIO) and 7-bromoindirubin-3 Prime -oxime (7BIO) in five different breast cancer cell lines. Cell viability assays identified that 6BIO and 7BIO are most effective in preventing the proliferation of the MDA-MB-231-TXSA breast cancer cell line from a total of five breast cancer cell lined examined. In addition it was found that the two compounds induce apoptosis via different mechanisms. 6BIO induces caspase-dependent programmed cell death through the intrinsic (mitochondrial) caspase-9 pathway. 7BIO up-regulates p21 and promotes G{sub 2}/M cell cycle arrest which is subsequently followed by the activation of two different apoptotic pathways: (a) a pathway that involves the upregulation of DR4/DR5 and activation of caspase-8 and (b) a caspase independent pathway. In conclusion, this study provides important insights regarding the molecular pathways leading to cell cycle arrest and apoptosis by two indirubin derivatives that can find clinical applications in targeted cancer therapeutics.

Binding of neutral molecules by p-nitrophenylureido substituted calix[4]arenes

Czech Academy of Sciences Publication Activity Database

Cuřínová, P.; Pojarová, M.; Budka, J.; Lang, Kamil; Stibor, I.; Lhoták, P.

2010-01-01

Roč. 66, č. 40 (2010), s. 8047-8050 ISSN 0040-4020 R&D Projects: GA ČR GA203/09/0691 Institutional research plan: CEZ:AV0Z40320502 Keywords : calixarene * recognition * neutral molecules binding * X-ray crystallography Subject RIV: CA - Inorganic Chemistry Impact factor: 3.011, year: 2010

Size effects on cation heats of formation. I. Methyl substitutions in nitrogenous compounds

International Nuclear Information System (INIS)

Leach, Sydney

2012-01-01

Graphical abstract: Heat of formation of cations as a function of ln(n) where n is the number of atoms in the ion: methyl substituted immonium cations. N = substitution at nitrogen sites, C = substitution at carbon sites. Highlights: ► Heats of formation of nitrogenous cations by graphical method relating to ion size. ► Methyl substitution in formamides, acetamides, immonium, amine, and imine cations. ► Methyl substitution in ammonium and amino cations. ► New studies ionization energies and heats of formation required in several cases. - Abstract: The heats of formation of molecular ions are often not known to better than 10 or 20 kJ/mol. The present study on nitrogenous compounds adopts the graphical approach of Holmes and Lossing which relates cation heats of formation to cation size. A study of methyl substitution in formamides and acetamides is followed by an examination of heat of formation data on carbon-site and nitrogen-site methyl substitution in immonium, amine, imine, ammonium and amino cations. The results provide tests of the validity of this graphical method and also suggest investigating or re-investigating the ionization energies and the heats of formation of several of the molecules studied.

Cloning retinoid and peroxisome proliferator-activated nuclear receptors of the Pacific oyster and in silico binding to environmental chemicals.

Directory of Open Access Journals (Sweden)

Susanne Vogeler

Full Text Available Disruption of nuclear receptors, a transcription factor superfamily regulating gene expression in animals, is one proposed mechanism through which pollution causes effects in aquatic invertebrates. Environmental pollutants have the ability to interfere with the receptor's functions through direct binding and inducing incorrect signals. Limited knowledge of invertebrate endocrinology and molecular regulatory mechanisms, however, impede the understanding of endocrine disruptive effects in many aquatic invertebrate species. Here, we isolated three nuclear receptors of the Pacific oyster, Crassostrea gigas: two isoforms of the retinoid X receptor, CgRXR-1 and CgRXR-2, a retinoic acid receptor ortholog CgRAR, and a peroxisome proliferator-activated receptor ortholog CgPPAR. Computer modelling of the receptors based on 3D crystal structures of human proteins was used to predict each receptor's ability to bind to different ligands in silico. CgRXR showed high potential to bind and be activated by 9-cis retinoic acid and the organotin tributyltin (TBT. Computer modelling of CgRAR revealed six residues in the ligand binding domain, which prevent the successful interaction with natural and synthetic retinoid ligands. This supports an existing theory of loss of retinoid binding in molluscan RARs. Modelling of CgPPAR was less reliable due to high discrepancies in sequence to its human ortholog. Yet, there are suggestions of binding to TBT, but not to rosiglitazone. The effect of potential receptor ligands on early oyster development was assessed after 24h of chemical exposure. TBT oxide (0.2μg/l, all-trans retinoic acid (ATRA (0.06 mg/L and perfluorooctanoic acid (20 mg/L showed high effects on development (>74% abnormal developed D-shelled larvae, while rosiglitazone (40 mg/L showed no effect. The results are discussed in relation to a putative direct (TBT disruption effect on nuclear receptors. The inability of direct binding of ATRA to CgRAR suggests

All-trans-retinoic acid enhances apoptosis induction by tyrosine kinase inhibitors in the eosinophilic leukemia-derived EoL-1 cell line.

Science.gov (United States)

Robert, Carine; Apàti, Agota; Chomienne, Christine; Papp, Béla

2008-02-01

Imatinib and retinoids induce apoptosis in FIP1L1/PDGFRalpha-positive EoL-1 leukemia cells. Although imatinib induces complete remission in most FIP1L1/PDGFRalpha-positive patients, response to imatinib is sometimes suboptimal. In order to enhance the potency of the molecularly targeted therapy of eosinophilic leukemia, we investigated the effect of retinoids combined with tyrosine kinase inhibitors on EoL-1 cells. We demonstrate that retinoids combined with tyrosine kinase inhibitors lead to enhanced apoptosis induction in EoL-1 cells. Our results suggest that tyrosine kinase inhibitors combined with retinoids may constitute a valuable therapeutic approach for sensitive neoplasias that may display enhanced anti-leukemic potency when compared to single drug treatments.

Design, synthesis, and herbicidal activity of novel substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives.

Science.gov (United States)

Xie, Yong; Chi, Hui-Wei; Guan, Ai-Ying; Liu, Chang-Ling; Ma, Hong-Juan; Cui, Dong-Liang

2014-12-31

A series of novel substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives were designed and synthesized using 2-phenylpridines as the lead compound by intermediate derivatization methods in an attempt to obtain novel compound candidates for weed control. The herbicidal activity assay in glasshouse tests showed several compounds (II6, II7, II8, II9, II10, II11, III2, III3, III4, and III5) could efficiently control velvet leaf, youth-and-old age, barnyard grass, and foxtail at the 37.5 g/ha active substance. Especially, the activities of II6, II7, III2, and III4 were proved roughly equivalent to the saflufenacil and better than 95% sulcotrione at the same concentration. The result of the herbicidal activity assay in field tests demonstrated that II7 at 60 g/ha active substance could give the same effect as bentazon at 1440 g/ha active substance to control dayflower and nightshade, meanwhile II7 showed better activity than oxyfluorfen to control arrowhead and security to rice. The present work indicates that II7 may be a novel compound candidate for potential herbicide.

Influence of substitution on the optical properties of functionalized pentacene monomers and crystals: Experiment and theory

KAUST Repository

Saeed, Yasir; Zhao, Kui; Singh, Nirpendra; Li, Ruipeng; Anthony, John Edward; Amassian, Aram; Schwingenschlö gl, Udo

2013-01-01

The influence of solubilizing substitutional groups on the electronic structure of prototypical functionalized pentacene molecules and crystals is studied by a combined experimental and theoretical approach. We experimentally establish

ESI(+-MS and GC-MS Study of the Hydrolysis of N-Azobenzyl Derivatives of Chitosan

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Fernanda S. Pereira

2014-10-01

Full Text Available New N-p-chloro-, N-p-bromo-, and N-p-nitrophenylazobenzylchitosan derivatives, as well as the corresponding azophenyl and azophenyl-p-sulfonic acids, were synthesized by coupling N-benzylvchitosan with aryl diazonium salts. The synthesized molecules were analyzed by UV-Vis, FT-IR, 1H-NMR and 15N-NMR spectroscopy. The capacity of copper chelation by these materials was studied by AAS. Chitosan and the derivatives were subjected to hydrolysis and the products were analyzed by ESI(+-MS and GC-MS, confirming the formation of N-benzyl chitosan. Furthermore, the MS results indicate that a nucleophilic aromatic substitution (SnAr reaction occurs under hydrolysis conditions, yielding chloroaniline from N-p-bromo-, and N-p-nitrophenylazo-benzylchitosan as well as bromoaniline from N-p-chloro-, and N-p-nitrophenylazobenzyl-chitosan.

Inhibition of type I NKT cells by retinoids or following sulfatide-mediated activation of type II NKT cells attenuates alcoholic liver disease

Science.gov (United States)

Maricic, Igor; Sheng, Huiming; Marrero, Idania; Seki, Ehikiro; Kisseleva, Tatiana; Chaturvedi, Som; Molle, Natasha; Mathews, K. Stephanie; Gao, Bin; Kumar, Vipin

2015-01-01

Innate immune mechanisms leading to liver injury following chronic alcohol ingestion are poorly understood. Natural killer T (NKT) cells, enriched in the liver and comprised of at least two distinct subsets, type I and type II, recognize different lipid antigens presented by CD1d molecules. We have investigated whether differential activation of NKT cell subsets orchestrates inflammatory events leading to alcoholic liver disease (ALD). We found that following chronic plus binge feeding of Lieber-DeCarli liquid diet in male C57BL/6 mice, type I but not type II NKT cells are activated leading to recruitment of inflammatory Gr-1highCD11b+ cells into liver. A central finding is that liver injury following alcohol feeding is dependent upon type I NKT cells. Thus liver injury is significantly inhibited in Jα18−/− mice deficient in type I NKT cells as well as following their inactivation by sulfatide-mediated activation of type II NKT cells. Furthermore we have identified a novel pathway involving all-trans retinoic acid (ATRA) and its receptor RARγ signaling that inhibits type I NKT cells and consequently ALD. A semi-quantitative PCR analysis of hepatic gene expression of some of the key proinflammatory molecules shared in human disease indicated that their upregulation in ALD is dependent upon type I NKT cells. Conclusion Type I but not type II NKT cells become activated following alcohol feeding. Type I NKT cells-induced inflammation and neutrophil recruitment results in liver tissue damage while type II NKT cells protect from injury in ALD. Inhibition of type I NKT cells by retinoids or by sulfatide prevents ALD. Since the CD1d pathway is highly conserved between mice and humans, NKT cell subsets might be targeted for potential therapeutic intervention in ALD. PMID:25477000

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

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Satoru Mori

2017-10-01

Full Text Available Phthalocyanines and subphthalocyanines are attracting attention as functional dyes that are applicable to organic solar cells, photodynamic therapy, organic electronic devices, and other applications. However, phthalocyanines are generally difficult to handle due to their strong ability to aggregate, so this property must be controlled for further applications of phthalocyanines. On the other hand, trifluoroethoxy-substituted phthalocyanines are known to suppress aggregation due to repulsion of the trifluoroethoxy group. Furthermore, the electronic characteristics of phthalocyanines are significantly changed by the strong electronegativity of fluorine. Therefore, it is expected that trifluoroethoxy-substituted phthalocyanines can be applied to new industrial fields. This review summarizes the synthesis and application of trifluoroethoxy-substituted phthalocyanine and subphthalocyanine derivatives.

Effects of a small molecule R-spondin-1 substitute RS-246204 on a mouse intestinal organoid culture.

Science.gov (United States)

Nam, Myeong-Ok; Hahn, Soojung; Jee, Joo Hyun; Hwang, Tae-Sun; Yoon, Ho; Lee, Dong Hyeon; Kwon, Min-Soo; Yoo, Jongman

2018-01-19

Organoids, a multi-cellular and organ-like structure cultured in vitro , can be used in a variety of fields such as disease modeling, drug discovery, or cell therapy development. When organoids derived from Lgr5 stem cells are cultured ex vivo , recombinant R-spondin-1 protein should be added at a high concentration for the initiation and maintenance of the organoids. Because the addition of large amounts of R-spondin-1 greatly increases the cost of organoids, the organoids grown with R-spondin-1 are not practical for large-scale drug screening and for the development of therapeutic agents. In this study, we tried to find a R-spondin-1 substitute compound that is able initiate small intestinal organoids without the use of the R-spondin-1 protein; thus, using organoid media that each included one compound from among an 8,364 compound library instead of R-spondin-1, we observed whether organoids were established from the crypts of the small intestine. As a result, we found one compound that could promote the initial formation and growth of enteroids in the medium without R-spondin-1 and named it RS-246204. The enteroids grown with RS-246204 had a similar differentiation capacity as well as self-renewal capacity as the enteroids grown with R-spondin-1. Furthermore, the RS-246204-derived enteroids could successfully produce the forskolin induced swelling and the organoid based epithelial to mesenchymal transition model. This compound could be used for developing a cost-efficient culturing method for intestinal organoids as well as for exploring Lgr5 signaling, intestinal stem cell physiology and therapeutics for GI tract diseases.

Asymmetric allylation of α-ketoester-derived N-benzoylhydrazones promoted by chiral sulfoxides/N-oxides Lewis bases: highly enantioselective synthesis of quaternary α-substituted α-allyl-α-amino acids.

Science.gov (United States)

Reyes-Rangel, Gloria; Bandala, Yamir; García-Flores, Fred; Juaristi, Eusebio

2013-09-01

Chiral sulfoxides/N-oxides (R)-1 and (R,R)-2 are effective chiral promoters in the enantioselective allylation of α-keto ester N-benzoylhydrazone derivatives 3a-g to generate the corresponding N-benzoylhydrazine derivatives 4a-g, with enantiomeric excesses as high as 98%. Representative hydrazine derivatives 4a-b were subsequently treated with SmI2, and the resulting amino esters 5a-b with LiOH to obtain quaternary α-substituted α-allyl α-amino acids 6a-b, whose absolute configuration was assigned as (S), with fundament on chemical correlation and electronic circular dichroism (ECD) data. © 2013 Wiley Periodicals, Inc.

Synthesis and Antimicrobial Activity of Some Novel Substituted Piperazinyl-quinazolin-3(4H-ones

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N. M. Raghavendra

2008-01-01

Full Text Available Several substituted-quinazolin-3(4H-ones were synthesized by condensation of 2-chloro-N-(4-oxo-substituted-quinazolin-3(4H-yl-acetamides with various substituted piperazines through single step reaction. Elemental analysis, IR, 1HNMR and mass spectral data confirmed the structure of the newly synthesized compounds. Synthesized quinazolin-4-one derivatives were investigated for their antibacterial and antifungal activities.

Effect of dipole moment and conformation on the mesophase behavior of di-laterally substituted phenylazophenyl benzoate liquid crystals

International Nuclear Information System (INIS)

Naoum, M.M.; Ahmed, H.A.

2011-01-01

Highlights: → Four homologous series of di-laterally substituted derivatives were prepared. → Measurement of the dipole moment and comparing it with those calculated for the various planner conformations. → Binary phase diagrams were constructed for mixtures made from any two analogues of different central lateral substituents. → Mesophase behavior is related to conformation. → The two molecules in all mixtures investigated are arranged in a back-to-face pattern. - Abstract: The dipole moments of the previously prepared 4-(3'-fluoro phenylazo)-2-(or 3-) substituted phenyl-4''-alkoxybenzoates (In a-d ), have been determined in benzene at 30 o C. The data obtained were compared with those theoretically calculated by molecular modeling program to deduce the most probable conformations for each individual homologous series. Probable conformations deduced were found to vary according to type and position of the lateral substituent attached to the central benzene ring. The results were used to correlate the mesophase behavior, in pure and mixed derivatives, with the conformation deduced for each series. Each homologous series, that have in common a lateral fluorine atom on the first terminal ring, differs from the other by a second lateral group substituted on the central ring. The latter group varies between 2-CH 3 , 3-CH 3 , 2-Cl and 3-CN groups. Within each homologous series, the number of carbons in the other terminal alkoxy group varies between 8 and 16 carbons. The study aims to investigate the steric effect of the spatial orientation of the central lateral substituent, based on deduced conformations, on the mesomorphic properties in their pure or mixed states. The mesophase behavior was investigated via differential scanning calorimetry, DSC, and mesophases identified by polarized light microscopy, PLM.

Removal potential of toxic 2378-substituted PCDD/F from incinerator flue gases by waste-derived activated carbons.

Science.gov (United States)

Hajizadeh, Yaghoub; Onwudili, Jude A; Williams, Paul T

2011-06-01

The application of activated carbons has become a commonly used emission control protocol for the removal or adsorption of persistent organic pollutants from the flue gas streams of waste incinerators. In this study, the 2378-substituted PCDD/F removal efficiency of three types of activated carbons derived from the pyrolysis of refuse derived fuel, textile waste and scrap tyre was investigated and compared with that of a commercial carbon. Experiments were carried out in a laboratory scale fixed-bed reactor under a simulated flue gas at 275°C with a reaction period of four days. The PCDD/F in the solid matrices and exhaust gas, were analyzed using gas chromatography coupled with a triple quadrupole mass spectrometer. In the absence of activated carbon adsorbent, there was a significant increase in the concentration of toxic PCDD/F produced in the reacted flyash, reaching up to 6.6 times higher than in the raw flyash. In addition, there was a substantial release of PCDD/F into the gas phase, which was found in the flue gas trapping system. By application of the different commercial, refuse derived fuel, textile and tyre activated carbons the total PCDD/F toxic equivalent removal efficiencies in the exhaust gas stream were 58%, 57%, 64% and 52%, respectively. In general, the removal of the PCDDs was much higher with an average of 85% compared to PCDFs at 41%. Analysis of the reacted activated carbons showed that there was some formation of PCDD/F, for instance, a total of 60.6 μg I-TEQ kg(-1) toxic PCDD/F was formed in the refuse derived fuel activated carbon compared to 34 μg I-TEQ kg(-1) in the commercial activated carbon. The activated carbons derived from the pyrolysis of waste, therefore, showed good potential as a control material for PCDD/F emissions in waste incinerator flue gases. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cheilitis in acne vulgaris patients with no previous use of systemic retinoid products.

Science.gov (United States)

Balighi, Kamran; Daneshpazhooh, Maryam; Lajevardi, Vahideh; Talebi, Shahin; Azizpour, Arghavan

2017-08-01

Isotretinoin is commonly used in the treatment of acne vulgaris. While one of the more common side-effects is cheilitis, we have observed an increased incidence of cheilitis prior to the commencement of systemic isotretinoin. The aim of this study was to assess the prevalence of cheilitis among acne vulgaris patients. A non-interventional cross-sectional study of patients with acne vulgaris. Patients with previous use of systemic retinoids were excluded. The patients were examined for signs and symptoms of cheilitis. Of a total of 400 patients, 134 (34%) had evidence of cheilitis at initial presentation. Two-thirds (63%) were female (P acne excorie, compared with only 8% of patients with no signs of cheilitis. Our findings suggest that cheilitis is quite common among acne vulgaris patients even before treatment with isotretinoin. © 2016 The Australasian College of Dermatologists.

Vitamin D receptor–retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation

Science.gov (United States)

de la Fuente, Alerie Guzman; Errea, Oihana; van Wijngaarden, Peter; Gonzalez, Ginez A.; Kerninon, Christophe; Jarjour, Andrew A.; Lewis, Hilary J.; Jones, Clare A.; Nait-Oumesmar, Brahim; Zhao, Chao; Huang, Jeffrey K.; ffrench-Constant, Charles

2015-01-01

The mechanisms regulating differentiation of oligodendrocyte (OLG) progenitor cells (OPCs) into mature OLGs are key to understanding myelination and remyelination. Signaling via the retinoid X receptor γ (RXR-γ) has been shown to be a positive regulator of OPC differentiation. However, the nuclear receptor (NR) binding partner of RXR-γ has not been established. In this study we show that RXR-γ binds to several NRs in OPCs and OLGs, one of which is vitamin D receptor (VDR). Using pharmacological and knockdown approaches we show that RXR–VDR signaling induces OPC differentiation and that VDR agonist vitamin D enhances OPC differentiation. We also show expression of VDR in OLG lineage cells in multiple sclerosis. Our data reveal a role for vitamin D in the regenerative component of demyelinating disease and identify a new target for remyelination medicines. PMID:26644513

Radioselective tritiation of acetanilide and para-substituted acetanilides

International Nuclear Information System (INIS)

Oohashi, K.; Nakamura, T.; Aoyama, Y.

1990-01-01

Acetanilide and para-substituted acetanilides were tritiated by heating with HTO in the presence of RhCl 3 .3H 2 O as a catalyst in an N,N-dimethylformamide solution at 105-107 deg C for 18 h. Under such conditions, tritium introduced into the anilide molecules was found at the adjacent ortho positions to the acetamido group with virtually 100% regioselectivity. The substituent effect on the rate of tritiation was observed. (author) 13 refs

Gold-catalyzed Alkyne Hydroxylation: Synthesis of 2-Substituted Benzo[b]furan Compounds

Institute of Scientific and Technical Information of China (English)

ZHANG Yuan; XIN Zhi-Jun; XUE Ji-Jun; LI Ying

2008-01-01

A strategy concerning the synthesis of 2-substituted benzo[b]furan compounds from o-alkynyl phenols via a gold-catalyzed alkyne hydroxylation is described, which allows the rapid synthesis of various 2-substituted benzo[b]furan derivatives in excellent yields under mild conditions. The o-alkynyl phenol precursors were readily prepared with a Sonogashira coupling reaction.

Morphology and Phase Transitions in Styrene-Butadiene-Styrene Triblock Copolymer Grafted with Isobutyl Substituted Polyhedral Oligomeric Silsesquioxanes (Postprint)

National Research Council Canada - National Science Library

Drazowski, Daniel B; Lee, Andre; Haddad, Timothy S

2007-01-01

Two symmetric triblock polystyrene-butadiene-polystyrene (SBS) copolymers with different styrene content were grafted with varying amounts of isobutyl-substituted polyhedral oligomeric silsesquioxane (POSS) molecules...

Morphology and Phase Transitions in Styrene-Butadiene-Styrene Triblock Copolymer Grafted with Isobutyl Substituted Polyhedral Oligomeric Silsesquioxanes (preprint)

National Research Council Canada - National Science Library

Drazkowski, Daniel B; Lee, Andre; Haddad, Timothy S

2006-01-01

Two symmetric triblock polystyrene-butadiene-polystyrene (SBS) copolymers with different styrene content were grafted with varying amounts of isobutyl-substituted polyhedral oligomeric silsesquioxane (POSS) molecules...

NADPH-d activity in rat thymus after the application of retinoid acid

Directory of Open Access Journals (Sweden)

F. Dorko

2012-02-01

Full Text Available The aim of this work was to determine the localization of nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d activity as the marker for synthesis of nitric oxide synthase (NOS in the rat thymus after the application of retinoid acid (RA on 1st, 7th, 14th and 21st days of gestation. The given results can build the basis for understanding of the role of NOS in rat thymus. NADPH-d positive cells were represented with dark-blue color and were localized on corticomedullar junction of the thymus. These cells were of different intensity of coloring and were shaped in oval, circle or irregular forms. NADPH-d positive nerve fibers were observed in perivascular topography. They were marked more strongly in the case of control group. The result of application of RA to gravid rats was that the birth weights of newborn rats and their thymuses were smaller, but without statistically significance.

Tautomerization and Dimerization of 6,13-Disubstituted Derivatives of Pentacene.

Science.gov (United States)

Garcia-Borràs, Marc; Konishi, Akihito; Waterloo, Andreas; Liang, Yong; Cao, Yang; Hetzer, Constantin; Lehnherr, Dan; Hampel, Frank; Houk, Kendall N; Tykwinski, Rik R

2017-05-02

Two new 6,13-disubstituted pentacene derivatives, 1 c and 1 d, with alkyl and triisopropylsilylethynyl substitution have been synthesized and characterized experimentally and computationally. The alkyl substituted 1 c and 1 d represent the first 6-alkyl-substituted pentacene derivative where the fully aromatic species dominates over the corresponding tautomer. Indeed, no tautomerization product is found for either 1 c or 1 d upon heating or in the presence of catalytic amounts of acid. On the other hand, an unexpected dimer (3 c) is formed from 1 c. A plausible mechanism for this new dimerization process of the 6-methyl-substituted pentacene derivative 1 c is proposed, which involves first a bimolecular hydrogen atom transfer followed by an intramolecular [4+2] Diels-Alder cycloaddition. In the case of 6-butyl substitution, neither tautomerization nor dimerization is observed. Computations support the proposed 1 c dehydrodimerization pathway, explain why 1 d does not dimerize, and show the importance of the nature of the group at C-13 in controlling the relative stability of 6-alkyl-substituted pentacene tautomers. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Successive substitution one-leg hybrid P-stable LMM for initial value ...

African Journals Online (AJOL)

This paper derives P-stable successive substitution one-leg hybrid linear multistep methods for the numerical solution of second order initial value problems in ordinary differential equations without explicit first order derivative. The methods are demonstrated by a numerical example also considered by Fatunla, et al (1997) ...

Ab initio calculations for the substitutions of Al(OH)4- and SO42- with Si tetrahedra

International Nuclear Information System (INIS)

Rahman, Md.Mazibur; Tanaka, Satoru; Nagasaki, Shinya

2001-01-01

We have studied the interaction phenomena for the substitutions of Al(OH) 4 - and SO 4 2- with both paired and bridging Si tetrahedra likely to be occurred in C-S-H gel coexisting with ettringite system. Gaussian 94 program has been used to obtain the total energy of the molecule in the optimized structure employing HF/3-21G level of theory. It has been investigated that the net charge on the substitution site causes the modification of the original structure during the substitution. The substitutions of Al(OH) 4 - with Si tetrahedra were found to be thermodynamically possible in both paired and bridging Si tetrahedra at chemical equilibrium. The substitutions of SO 4 2- with Si tetrahedra were found to be thermodynamically possible at the limited positions as well. It this work, these possibilities are also discussed with the estimated activated energies for the substitutions of Al(OH) 4 - and SO 4 2- with paired Si tetrahedra. (author)

Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H-quino[3,4-b][1,4]benzothiazine Derivatives

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Andrzej Zięba

2016-11-01

Full Text Available A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group in position 10 of the parent (quinobenzothiazine system. Antiproliferative activity of the synthesized compounds was studied using cultured neoplastic cells (MDA-MB-231, SNB-19, and C-32 cell lines. Four selected compounds were investigated in more detail for cytotoxicity and antiproliferative effect. Transcriptional activity of genes regulating cell cycle (TP53, apoptosis (BAX, BCL-2, as well as proliferation (H3 were assessed. Finally, the ability of the selected compounds to bind DNA was checked in the presence of ethidium bromide.

A zeta potential value determines the aggregate's size of penta-substituted [60]fullerene derivatives in aqueous suspension whereas positive charge is required for toxicity against bacterial cells.

Science.gov (United States)

Deryabin, Dmitry G; Efremova, Ludmila V; Vasilchenko, Alexey S; Saidakova, Evgeniya V; Sizova, Elena A; Troshin, Pavel A; Zhilenkov, Alexander V; Khakina, Ekaterina A; Khakina, Ekaterina E

2015-08-08

The cause-effect relationships between physicochemical properties of amphiphilic [60]fullerene derivatives and their toxicity against bacterial cells have not yet been clarified. In this study, we report how the differences in the chemical structure of organic addends in 10 originally synthesized penta-substituted [60]fullerene derivatives modulate their zeta potential and aggregate's size in salt-free and salt-added aqueous suspensions as well as how these physicochemical characteristics affect the bioenergetics of freshwater Escherichia coli and marine Photobacterium phosphoreum bacteria. Dynamic light scattering, laser Doppler micro-electrophoresis, agarose gel electrophoresis, atomic force microscopy, and bioluminescence inhibition assay were used to characterize the fullerene aggregation behavior in aqueous solution and their interaction with the bacterial cell surface, following zeta potential changes and toxic effects. Dynamic light scattering results indicated the formation of self-assembled [60]fullerene aggregates in aqueous suspensions. The measurement of the zeta potential of the particles revealed that they have different surface charges. The relationship between these physicochemical characteristics was presented as an exponential regression that correctly described the dependence of the aggregate's size of penta-substituted [60]fullerene derivatives in salt-free aqueous suspension from zeta potential value. The prevalence of DLVO-related effects was shown in salt-added aqueous suspension that decreased zeta potential values and affected the aggregation of [60]fullerene derivatives expressed differently for individual compounds. A bioluminescence inhibition assay demonstrated that the toxic effect of [60]fullerene derivatives against E. coli cells was strictly determined by their positive zeta potential charge value being weakened against P. phosphoreum cells in an aquatic system of high salinity. Atomic force microscopy data suggested that the

Tissue reaction and material characteristics of four bone substitutes

DEFF Research Database (Denmark)

Jensen, S S; Aaboe, M; Pinholt, E M

1996-01-01

and Interpore 500 HA/CC) were implanted into 5-mm bur holes in rabbit tibiae. There was no difference in the amount of newly formed bone around the four biomaterials. Interpore 500 HA/CC resorbed completely, whereas the other three biomaterials did not undergo any detectable biodegradation. Bio......The aim of the present study was to qualitatively and quantitatively compare the tissue reactions around four different bone substitutes used in orthopedic and craniofacial surgery. Cylinders of two bovine bone substitutes (Endobon and Bio-Oss) and two coral-derived bone substitutes (Pro Osteon 500......-Oss was osseointegrated to a higher degree than the other biomaterials. Material characteristics obtained by diffuse reflectance infrared Fourier transform spectrometry analysis and energy-dispersive spectrometry did not explain the differences in biologic behavior....

Influence of thermocleavable functionality on organic field-effect transistor performance of small molecules

Science.gov (United States)

Mahale, Rajashree Y.; Dharmapurikar, Satej S.; Chini, Mrinmoy Kumar; Venugopalan, Vijay

2017-06-01

Diketopyrrolopyrrole based donor-acceptor-donor conjugated small molecules using ethylene dioxythiophene as a donor was synthesized. Electron deficient diketopyrrolopyrrole unit was substituted with thermocleavable (tert-butyl acetate) side chains. The thermal treatment of the molecules at 160 °C eliminated the tert-butyl ester group results in the formation of corresponding acid. Optical and theoretical studies revealed that the molecules adopted a change in molecular arrangement after thermolysis. The conjugated small molecules possessed p-channel charge transport characteristics in organic field effect transistors. The charge carrier mobility was increased after thermolysis of tert-butyl ester group to 5.07 × 10-5 cm2/V s.

Biofuels: from microbes to molecules

National Research Council Canada - National Science Library

Lu, Xuefeng

2014-01-01

.... The production of different biofuel molecules including hydrogen, methane, ethanol, butanol, higher chain alcohols, isoprenoids and fatty acid derivatives, from genetically engineered microbes...

Effects of a synthetic retinoid on skin structure, matrix metalloproteinases, and procollagen in healthy and high-risk subjects with diabetes.

Science.gov (United States)

Zeng, Wei; Tahrani, Abd; Shakher, Jayadave; Varani, James; Hughes, Sharon; Dubb, Kiran; Stevens, Martin J

2011-01-01

In diabetes, foot ulceration may result from increased skin fragility. Retinoids can reverse some diabetes-induced deficits of skin structure and function, but their clinical utility is limited by skin irritation. The effects of diabetes and MDI 301, a nonirritating synthetic retinoid, and retinoic acid have been evaluated on matrix metalloproteinases (MMPs), procollagen expression, and skin structure in skin biopsies from nondiabetic volunteers and diabetic subjects at risk of foot ulceration using organ culture techniques. Zymography and enzyme-linked immunosorbent assay were utilized for analysis of MMP-1, -2, and -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) and immunohistochemistry for type I procollagen protein abundance. Collagen structure parameters were assessed in formalin-fixed, paraffin-embedded tissue sections. The % of active MMP-1 and -9 was higher and TIMP-1 abundance was lower in subjects with diabetes. Type 1 procollagen abundance was reduced and skin structural deficits were increased in diabetes. Three μM MDI 301 reduced active MMP-1 and -9 abundance by 29% (P structural deficit scores. Two μM retinoic acid reduced MMP-1 but did not significantly affect skin structure. These data indicate that diabetic patients at risk of foot ulceration have deficits of skin structure and function. MDI 301 offers potential for repairing this skin damage complicating diabetes. Copyright © 2011 Elsevier Inc. All rights reserved.

Synthesis and Positive Inotropic Activity of [1,2,4]Triazolo[4,3-a] Quinoxaline Derivatives Bearing Substituted Benzylpiperazine and Benzoylpiperazine Moieties

Directory of Open Access Journals (Sweden)

Xue-Kun Liu

2017-02-01

Full Text Available In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone. Compound 6c was the most potent agent, with an increased stroke volume of 12.53% ± 0.30% (milrinone: 2.46% ± 0.07% at 3 × 10−5 M. The chronotropic effects of compounds having considerable inotropic effects were also evaluated.

Synthesis and antitumor evaluation of some new N4 substituted sulfa pyridine derivatives with studying the synergistic effect of γ-irradiation

International Nuclear Information System (INIS)

Elsaid Agha, H.M.S.

2011-01-01

The aim of the present investigation is to synthesize a new class of N 4 substituted sulfa pyridine derivatives with anticipated cytotoxic activity. All the newly synthesized compounds were screened for their in-vitro cytotoxic activity against breast cancer cell line (MCF-7) compared to the reference drug Doxorubicin. Also the synergism of the most potent synthesized compounds with γ- radiation was studied. Moreover, a molecular docking study was carried out by docking the most active synthesized compounds in the active site of Cyclin Dependent Kinase 2 receptor to assess their inhibitory effect upon this enzyme as this may have a role in their anticancer activity.

Annulated Dialkoxybenzenes as Catholyte Materials for Non-aqueous Redox Flow Batteries: Achieving High Chemical Stability through Bicyclic Substitution

International Nuclear Information System (INIS)

Zhang, Jingjing; Yang, Zheng; Shkrob, Ilya A.; Assary, Rajeev S.

2017-01-01

1,4-Dimethoxybenzene derivatives are materials of choice for use as catholytes in nonaqueous redox flow batteries, as they exhibit high open-circuit potentials and excellent electrochemical reversibility. However, chemical stability of these materials in their oxidized form needs to be improved. Disubstitution in the arene ring is used to suppress parasitic reactions of their radical cations, but this does not fully prevent ring-addition reactions. By incorporating bicyclic substitutions and ether chains into the dialkoxybenzenes, a novel catholyte molecule, 9,10-bis(2-methoxyethoxy)-1,2,3,4,5,6,7,8-octahydro-1,4:5, 8-dimethanenoanthracene (BODMA), is obtained and exhibits greater solubility and superior chemical stability in the charged state. As a result, a hybrid flow cell containing BODMA is operated for 150 charge–discharge cycles with minimal loss of capacity.

Synthesis, characterization of N-, S-, O-substituted naphtho- and ...

Indian Academy of Sciences (India)

obtained on a Thermo Finnigan LCQ Advantage MAX. LC/MS/MS spectrometer .... organic layer was washed with water (4 × 30 mL), and dried with Na2SO4. ..... mono(thio)-substituted compounds containing chlorine atom derivatives were.

Design and synthesis of dimethylaminomethyl-substituted curcumin derivatives/analogues: potent antitumor and antioxidant activity, improved stability and aqueous solubility compared with curcumin.

Science.gov (United States)

Fang, Xubin; Fang, Lei; Gou, Shaohua; Cheng, Lin

2013-03-01

A series of dimethylaminomethyl-substituted curcumin derivatives/analogues were designed and synthesized. All compounds effectively inhibited HepG2, SGC-7901, A549 and HCT-116 tumor cell lines proliferation in MTT assay. Particularly, compounds 2a and 3d showed much better activity than curcumin against all of the four tumor cell lines. Antioxidant test revealed that these compounds had higher free radical scavenging activity than curcumin towards both DPPH and galvinoxyl radicals. Furthermore, the aqueous solubility and stability of the target compounds were also significantly improved compared with curcumin. Copyright © 2013 Elsevier Ltd. All rights reserved.

Electric Dipole Transition Moments and Solvent-Dependent Interactions of Fluorescent Boron-Nitrogen Substituted Indole Derivatives.

Science.gov (United States)

Saif, Mari; Widom, Julia R; Xu, Senmiao; Abbey, Eric R; Liu, Shih-Yuan; Marcus, Andrew H

2015-06-25

Fluorescent analogues of the indole side chain of tryptophan can be useful spectroscopic probes of protein-protein and protein-DNA interactions. Here we present linear dichroism and solvent-dependent spectroscopic studies of two fluorescent analogues of indole, in which the organic C═C unit is substituted with the isosteric inorganic B-N unit. We studied the so-called "external" BN indole, which has C2v symmetry, and the "fused" BN indole with Cs symmetry. We performed a combination of absorption and fluorescence spectroscopy, ultraviolet linear dichroism (UV-LD) in stretched poly(ethylene) (PE) films, and quantum chemical calculations on both BN indole compounds. Our measurements allowed us to characterize the degree of alignment for both molecules in stretched PE films. We thus determined the orientations and magnitudes of the two lowest energy electric dipole transition moments (EDTMs) for external BN indole, and the two lowest energy EDTMs for fused BN indole within the 30 000-45 000 cm(-1) spectral range. We compared our experimental results to those of quantum chemical calculations using standard density functional theory (DFT). Our theoretical predictions for the low-energy EDTMs are in good agreement with our experimental data. The absorption and fluorescence spectra of the external and the fused BN indoles are sensitive to solvent polarity. Our results indicate that the fused BN indole experiences much greater solvation interactions with polar solvents than does the external BN indole.

Bis-aryl substituted dioxaborines as electron-transport materials: a comparative density functional theory investigation with oxadiazoles and siloles

International Nuclear Information System (INIS)

Risko, C.; Zojer, E.; Brocorens, P.; Marder, S.R.; Bredas, J.L.

2005-01-01

We report on a detailed quantum-chemical comparison of the electronic structures, vertical electron affinities, and intramolecular reorganization energies for bis-aryl substituted dioxaborine, oxadiazole, and silole derivatives. The results indicate that the HOMO and LUMO energies of the substituted compounds can be tuned on the order of 2-3 eV via minor changes in the substitution patterns, with the HOMO and LUMO levels for the dioxaborine derivatives consistently the most energy stabilized. Additionally, large vertical electron affinities and comparable intramolecular reorganization energies confirm that dioxaborine systems are interesting candidates for electron transport materials

Influence on the interaction by functional groups in some series of bicyclo (2,2,1) heptane derivatives

International Nuclear Information System (INIS)

Gagnaire, Genevieve

1971-01-01

In connection with investigations involving the interactions of substituted groups in the bicyclo (2,2,1) heptane molecules, the chemical reactivity and some physical properties of polyfunctional compounds have been studied. A new method for preparation of β-fenchylic derivatives is presented, the first described terpenic nitroxide radical have been prepared from oxazolidinic compounds. The stereochemistry of the base induced elimination reaction of 6-exo tosyl and 6-endo tosyl oxy epi-camphor is dependent of the geometry of these compounds. On the other hand, the results indicate that the most important part of the structure is the position of the carbonyl group. Tricyclenic and camphenic derivatives are obtained with different rates. An explanation for these results involve several possible basic abstractions of acid protons, and the competition between these different reactions. The oxazolidinic compounds are obtained by reacting 2-amino 2-methyl 1-propanol with norcamphor and norbornane-2,5 dione. The geometrical configuration of the different stereoisomers is deduced from the measured dipolar interaction parameter D. The cotton effects of the γ-diketones do not show any interaction between the two carbonyl groups, in the fenchylic and bornylic series. The two carbonyl bond angles of the substituted α-diketones do not seem to be sensitive to any substitution of an alkoxy group. So, a new quadrant rule is proposed; compatible results are obtained, except for a methyl group in the α position. At least, PMR studies of terpenic polyfunctional compounds demonstrate the influence of the substitution on the geometry of the carbon skeleton. A new coupling constant 4 J HH is examined. (author) [fr

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

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Michele Mari

2014-08-01

Full Text Available The reaction of 3-substituted indoles with dehydroalanine (Dha derivatives under Lewis acid-mediated conditions has been investigated. The formation of 2-substituted tryptophans is proposed to occur through a selective alkylative dearomatization–cyclization followed by C3- to C2-alkyl migration and rearomatization.

Hydrogen/deuterium substitution methods: understanding water structure in solution

International Nuclear Information System (INIS)

Soper, A.K.

1993-01-01

The hydrogen/deuterium substitution method has been used for different applications, such as the short range order between water molecules in a number of different environments (aqueous solutions of organic molecules), or to study the partial structure factors of water at high pressure and temperature. The absolute accuracy that can be obtained remains uncertain, but important qualitative information can be obtained on the local organization of water in aqueous solution. Some recent results with pure water, methanol and dimethyl sulphoxide (DMSO) solutions are presented. It is shown that the short range water structure is not greatly affected by most solutes except at high concentrations and when the solute species has its own distinctive interaction with water (such as a dissolved small ion). 3 figs., 14 refs

Green Production of Indolylquinones, Derivatives of Perezone, and Related Molecules, Promising Antineoplastic Compounds

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René Gerardo Escobedo-González

2016-01-01

Full Text Available A green approach to produce the indolyl derivatives from four natural quinones (perezone, isoperezone, menadione, and plumbagin was performed; in this regard, a comparative study was accomplished among the typical mantle heating and three nonconventional activating modes of reaction (microwave, near-infrared, and high speed ball milling or tribochemical, under solventless conditions and using bentonitic clay as a catalyst. In addition, the tribochemical production of isoperezone from perezone is also commented on. It is also worth noting that the cytotoxicity of the synthesized indolylquinones in human breast cancer cell was tested by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay, with the 3-indolylisoperezone being the most active. The structural attribution of the target molecules was performed by typical spectroscopic procedures; moreover, the experimental and computed 1H and 13C NMR chemical shifts data, with previous acquisition of the corresponding minimum energetic structures, were in good agreement.

One-pot, three-component synthesis of highly substituted pyridines ...

Indian Academy of Sciences (India)

Administrator

trile in the presence of nanocrystalline magnesium oxide provides the highly substituted pyridine derivatives in moderate to ..... NAP–MgO (0⋅1 g), ethanol (5 mL) at reflux temperature b ... difference in the electronic and steric properties of.

Marine-derived biological macromolecule-based biomaterials for wound healing and skin tissue regeneration.

Science.gov (United States)

Chandika, Pathum; Ko, Seok-Chun; Jung, Won-Kyo

2015-01-01

Wound healing is a complex biological process that depends on the wound condition, the patient's health, and the physicochemical support given through external materials. The development of bioactive molecules and engineered tissue substitutes to provide physiochemical support to enhance the wound healing process plays a key role in advancing wound-care management. Thus, identification of ideal molecules in wound treatment is still in progress. The discovery of natural products that contain ideal molecules for skin tissue regeneration has been greatly advanced by exploration of the marine bioenvironment. Consequently, tremendously diverse marine organisms have become a great source of numerous biological macromolecules that can be used to develop tissue-engineered substitutes with wound healing properties. This review summarizes the wound healing process, the properties of macromolecules from marine organisms, and the involvement of these molecules in skin tissue regeneration applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Chlorine- and Sulphur-substituted Pyrrolo[3,4-b]quinolines and ...

African Journals Online (AJOL)

Chlorine- and Sulphur-substituted Pyrrolo[3,4-b]quinolines and Related Derivatives .... J. Chem., 2003, 56, 40–46,. . .... It is evident from the above that by judicious selection and application of reagents ...

Synthesis, Characterization, Antimicrobial Screening and Free-Radical Scavenging Activity of Some Novel Substituted Pyrazoles

Directory of Open Access Journals (Sweden)

Nagwa Mohamed Mahrous Hamada

2015-06-01

Full Text Available The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same time 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were prepared from the reaction of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide, respectively. The synthesized compounds were structurally characterized on the basis of IR, 1H-NMR, 13C-NMR spectral data and microanalyses. All of the newly isolated compounds were tested for their antimicrobial activities. The antimicrobial screening using the agar well-diffusion method revealed that the chloro derivatives are the most active ones. Moreover, the antioxidant and anti-inflammatory activity of these chloro derivatives are also studied using the DPPH radical scavenging and NO radical scavenging methods, respectively.

Synthesis and antibacterial activities of N-substituted maleopimarimide

Directory of Open Access Journals (Sweden)

LI Hui

2016-02-01

Full Text Available With Macrogol 600(PEG-600 as solvent and toluene as dehydrant,eight N-Substituted maleopimarimide compounds were synthesized from maleopimaric acid and aniline or its derivatives by one-step reaction;Their structures were confirmed and the antimicrobial activities of these compounds were also preliminarily investigated.

Crystal structures of three 4-substituted-2,2′-bipyridines synthesized by Sonogashira and Suzuki–Miyaura cross-coupling reactions

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Thuy Luong Thi Thu

2017-04-01

Full Text Available Facile synthetic routes for three 4-substituted 2,2′-bipyridine derivatives, 4-[2-(4-methylphenylethynyl]-2,2′-bipyridine, C19H14N2, (I, 4-[2-(pyridin-3-ylethynyl]-2,2′-bipyridine, C17H11N3, (II, and 4-(indol-4-yl-2,2′-bipyridine, C18H13N3, (III, via Sonogashira and Suzuki–Miyaura cross-coupling reactions, respectively, are described. As indicated by X-ray analysis, the 2,2′-bipyridine core, the ethylene linkage and the substituents of (I and (II are almost planar [dihedral angles between the two ring systems: 8.98 (5 and 9.90 (6° for the two molecules of (I in the asymmetric unit and 2.66 (14° for (II], allowing π-conjugation. On the contrary, in (III, the indole substituent ring is rotated significantly out of the bipyridine plane [dihedral angle = 55.82 (3°], due to steric hindrance. The crystal packings of (I and (II are dominated by π–π interactions, resulting in layers of molecules parallel to (30-2 in (I and columns of molecules along the a axis in (II. The packing of (III exhibits zigzag chains of molecules along the c axis interacting through N—H...N hydrogen bonds and π–π interactions. The contributions of unknown disordered solvent molecules to the diffraction intensities in (II were removed with the SQUEEZE [Spek (2015. Acta Cryst. C71, 9–18] algorithm of PLATON. The given chemical formula and other crystal data do not take into account these solvent molecules.

Novel biotransformation process of podophyllotoxin to 4 β-sulfur-substituted podophyllum derivates with anti-tumor activity by Penicillium purpurogenum Y.J. Tang.

Science.gov (United States)

Bai, J-K; Zhao, W; Li, H-M; Tang, Y-J

2012-01-01

According to the structure-function relationship of podophyllotoxin (PTOX) and its analogue of 4'- demethylepipodophyllotoxin (DMEP), the 4 β-substitution of sulfur-containing heterocyclic compounds with a carbon-sulfur bond at 4 position of PTOX or DMEP is an essential modification direction for improving the anti-tumor activity. So, four novel 4 β-sulfursubstituted podophyllum derivatives (i.e., 4β -(1,2,4-triazole-3-yl)sulfanyl-4-deoxy-podophyllotoxin (4-MT-PTOX), 4β-(1,3,4- thiadiazole-2-yl)sulfanyl-4-deoxy-podophyllotoxin (4-MTD-PTOX), 4β-(1,2,4-triazole-3-yl)sulfanyl-4-deoxy-4' -demethylepipodophyllotoxin (4-MT-DMEP), and 4β-(1,3,4-thiadiazole-2-yl)sulfanyl-4-deoxy-4'-demethylepipodophyllotoxin (4-MTD-DMEP)) were designed and then successfully biosynthesized in this work. In the novel sulfur-substituted biotransformation processes, PTOX and DMEP was linked with sulfur-containing compounds (i.e., 3-mercapto-1,2,4-triazole (MT) and 2-mercapto-1,3,4-thiadiazole (MTD)) at 4 position of cycloparaffin to produce 4-MT-PTOX (1), 4-MTD-PTOX (2), 4-MT-DMEP (3), and 4-MTD-DMEP (4) by Penicillium purpurogenum Y.J. Tang, respectively, which was screened out from Diphylleia sinensis Li (Hubei, China). All the novel compounds exhibited promising in vitro bioactivity, especially 4-MT-PTOX (1). Compared with etoposide (i.e., a 50 % effective concentration [EC(50)] of 25.72, 167.97, and 1.15 M), the EC(50) values of 4-MT-PTOX (1) against tumor cell line BGC-823, A549 and HepG2 (i.e., 0.28, 0.76, and 0.42 M) were significantly improved by 91, 221 and 2.73 times, respectively. Moreover, the EC(50) value of 4-MT-PTOX (1) against the normal human cell line HK-2 (i.e., 182.4 μM) was 19 times higher than that of etoposide (i.e., 9.17 μM). Based on the rational design, four novel 4 β-sulfur-substituted podophyllum derivatives with superior in vitro anti-tumor activity were obtained for the first time. The correctness of structure-function relationship and rational drug

Synthesis and biological activity of novel series of 4-methoxy, and 4,9-dimethoxy-5-substituted furo[2,3-g]-1,2,3-benzoxathiazine-7,7-dioxide derivatives.

Science.gov (United States)

El-Sawy, Eslam R; Ebaid, Manal S; Abo-Salem, Heba M; El-Hallouty, Salwa; Kassem, Emad M; Mandour, Adel H

2014-05-01

A novel series of 4-methoxy, and 4,9-dimethoxy-5-substituted furo[2,3-g]-1,2,3-benzoxathiazine-7,7-dioxide derivatives 3a,b, 10a-g and 11a-g were prepared in good yields via the reaction of 4-methoxy (1a) and 4,7-dimethoxy-5-acetyl-6-hydroxybenzofurans (1b) and their α,β-unsaturated keto derivatives 6a-g and 7a-g with chlorosulfonyl isocyanate (CSI). On the other hand, N-chlorosulfonyl carbamate derivatives 4a,b, 12a,b and 13a,b were prepared and allowed to react with piperidine to give the corresponding N-piperidinosulfonyl carbamate derivatives 5a,b, 14a,b and 15a,b, respectively. Sixteen new target compounds 3a,b, 10a-g, and 11a-g were tested for their DPPH radical-scavenging, and in vitro antiproliferative activity against A-549, MCF7 and HCT-116 cancer cell lines. Compounds 10a, 11c, 11e, and 11g showed moderate DPPH radical-scavenging activity compared to ascorbic acid at 100 μg/mL. 4,9-Dimethoxy-5-substituted styrylfuro[3,2-g]-1,2,3-benzoxathiazine-7,7-dioxides 11a, 11b, and 11c were found to be highly active against A-549 and HCT-116 cancer cell lines with IC50 values ranging from 0.02 to 0.08 μmol/mL compared to doxorubicin with IC50 = 0.04 and 0.06 μmol/mL, respectively.

Synthesis of N-substituted acetamide derivatives of azinane-bearing ...

African Journals Online (AJOL)

The search for new drug candidates with more bioactivity potential is a key research interest in synthetic organic chemistry [1]. The derivatives of heterocyclic compounds have been found to be bioactive, including naturally occurring and synthetically prepared ones [2]. Among these compounds, 1,3,4-oxadiazole derivatives ...

Adsorption of ethyl xanthate on ZnS(110) surface in the presence of water molecules: A DFT study

Energy Technology Data Exchange (ETDEWEB)

Long, Xianhao [School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004 (China); Chen, Jianhua, E-mail: jhchen@gxu.edu.cn [School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004 (China); Guangxi Colleges and University Key Laboratory of Minerals Engineering, 530004 (China); Chen, Ye, E-mail: fby18@126.com [College of Resources and Metallurgy, Guangxi University, Nanning 530004 (China)

2016-05-01

Graphical abstract: - Highlights: • Adsorption of water molecules decreases the reactivity of surface Zn atom. • Copper impurities decrease the band gap of ZnS surface. • Copper impurities enhance the adsorption of xanthate on the ZnS surface. • Water molecules have little influence on the properties of Cu-substituted ZnS surface. • The xanthate S atom can interact with the surface S atom of Cu-substituted ZnS surface. - Abstracts: The interaction of collector with the mineral surface plays a very important role in the froth flotation of sphalerite. The adsorptions occurred at the interface between the mineral surface and waters; however most of DFT simulations are performed in vacuum, without consideration of water effect. Semiconductor surface has an obvious proximity effect, which will greatly influence the surface reactivity. To understand the mechanism of xanthate interacting with sphalerite surface in the presence of water molecules, the ethyl xanthate molecule adsorption on un-activated and Cu-activated ZnS(110) surface in the absence and presence of water molecules were performed using the density functional theory (DFT) method. The calculated results show that the adsorption of water molecules dramatically changes the properties of ZnS surface, resulting in decreasing the reactivity of surface Zn atoms with xanthate. Copper activation of ZnS surface changes the surface properties, leading to the totally different adsorption behaviors of xanthate. The presence of waters has little influence on the properties of Cu-activated ZnS surface. The xanthate S atom can interact with the surface S atom of Cu-substituted ZnS surface, which would result in the formation of dixanthogen.

The clinical impact of vehicle technology using a patented formulation of benzoyl peroxide 5%/clindamycin 1% gel: comparative assessments of skin tolerability and evaluation of combination use with a topical retinoid.

Science.gov (United States)

Del Rosso, James Q; Tanghetti, Emil

2006-02-01

A major challenge encountered in clinical practice in patients with acne vulgaris is irritation related to topical medications used for treatment. Advances in vehicle technology have improved formulations containing active ingredients known to produce irritation in some patients, such as benzoyl peroxide (BP) and topical retinoids. Clinical studies, including combination therapy studies have demonstrated that certain additives, such as silicates and specific humectants, reduce irritation by maintaining barrier integrity. A patented gel formulation of BP 5%/clindamycin phosphate 1% (clindamycin) containing dimethicone and glycerin has been studied both as a monotherapy and in combination with topical retinoid use. This article evaluates specific vehicle additives included in this gel formulation and explains their role in reducing irritation. Data from clinical trials utilizing this technology in acne management are also reviewed.

Anti-cancer Lead Molecule

KAUST Repository

Sagar, Sunil; Kaur, Mandeep; Esau, Luke E.

2014-01-01

Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic drugs

Anti-cancer Lead Molecule

KAUST Repository

Sagar, Sunil

2014-04-17

Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic drugs

Generation time, life history and the substitution rate of neutral mutations.

Science.gov (United States)

Lehtonen, Jussi; Lanfear, Robert

2014-11-01

Our understanding of molecular evolution is hampered by a lack of quantitative predictions about how life-history (LH) traits should correlate with substitution rates. Comparative studies have shown that neutral substitution rates vary substantially between species, and evidence shows that much of this diversity is associated with variation in LH traits. However, while these studies often agree, some unexplained and contradictory results have emerged. Explaining these results is difficult without a clear theoretical understanding of the problem. In this study, we derive predictions for the relationships between LH traits and substitution rates in iteroparous species by using demographic theory to relate commonly measured life-history traits to genetic generation time, and by implication to neutral substitution rates. This provides some surprisingly simple explanations for otherwise confusing patterns, such as the association between fecundity and substitution rates. The same framework can be applied to more complex life histories if full life-tables are available. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Chemical and serologic definition of two unique D region-encoded molecules in the wild-derived mouse strain B10.GAA37.

Science.gov (United States)

Lillehoj, E P; Walsh, W D; Potter, T; Lee, D R; Coligan, J E; Hansen, T H

1984-12-01

Detailed serologic and biochemical characterization of D region products of the wild-derived mouse strain B10.GAA37 (Dw16) were performed and compared with previous studies of the D region products of the H-2d,b, and q haplotypes. Serologic analysis revealed that the antigens encoded by the Dw16 region express a unique combination of specificities defined by monoclonal antibodies (mAb) with established activity for the Ld and Dd molecules. Two out of five anti-Ld-reactive mAb reacted with B10.GAA37 cells, whereas one of three anti-Dd mAb showed B10.GAA37 reactivity. Sequential immunoprecipitation of B10.GAA37 antigens demonstrated the existence of at least two antigenically distinct molecules (designated Dw16 and Lw16) encoded by genes associated with the Dw16 region. Peptide map comparisons of the Dw16 and Lw16 molecules defined multiple differences in their primary protein structure, suggesting they are products of separate genes. Structural comparisons of the Lw16 and Dw16 molecules with the Ld and Dd molecules implied a) that the Dw16 and Dd regions did not result from a recent evolutionary divergence of a common primordial haplotype, and b) that the Lw16 and Dw16 molecules are more structurally homologous to each other than the Ld and Dd molecules are. Comparison of these findings with our previous studies of antigens encoded by the D regions suggest that each of these haplotypes has unique properties in terms of the number of gene products expressed and/or the structural relatedness of products of the same region.

Synthesis, characterization and pharmacological evaluation of different 1,3,4-oxadiazole and acetamide derivatives of ethyl nipecotate

Directory of Open Access Journals (Sweden)

Khadija Nafeesa

2017-12-01

Full Text Available A new series of N-substituted derivatives of 2-[(5-{1-[(4-chlorophenylsulfonyl]-3-piperidinyl}-1,3,4-oxadiazol-2-ylsulfanyl]acetamide (6a-w has been designed and synthesized with multifunctional moieties. The synthesized compounds were evaluated for their antibacterial and anti-enzymatic potential supported by % hemolytic activity. The synthesized compound 5-(1-(4-chlorophenylsulfonyl-3-piperidinyl-1,3,4-oxadiazole-2-thiol (3 was stirred with synthesized electrophiles as N-aryl/alkyl/aralkyl-2-bromoacetamide (5a-w in an aprotic solvent under basic conditions to acquire the target molecules, 6a-w. The spectral analytical techniques of IR, EI-MS, 1H NMR and 13C-NMR were utilized for structural elucidation of synthesized molecules. The antibacterial screening against certain bacterial strains of gram-negative and gram-positive bacteria rendered compound 6i as good inhibitor of gram-negative bacterial strains. The enzyme inhibition revealed low potential against lipoxygenase (LOX enzyme. The hemolytic study provided valuable information about cytotoxic behavior of synthesized molecules. Keywords: 1,3,4-Oxadiazole, Acetamide, Antibacterial activity, Hemolytic activity, Lipoxygenase inhibition

Regioselective 1-N-Alkylation and Rearrangement of Adenosine Derivatives.

Science.gov (United States)

Oslovsky, Vladimir E; Drenichev, Mikhail S; Mikhailov, Sergey N

2015-01-01

Several methods for the preparation of some N(6)-substituted adenosines based on selective 1-N-alkylation with subsequent Dimroth rearrangement were developed. The proposed methods seem to be effective for the preparation of natural N(6)-isopentenyl- and N(6)-benzyladenosines, which are known to possess pronounced biological activities. Direct 1-N-alkylation of 2',3',5'-tri-O-acetyladenosine and 3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides in N,N-dimethylformamide (DMF) in the presence of BaCO3 and KI gave 1-N-substituted derivatives with quantitative yields, whereas 1-N-alkylation of adenosine was accompanied by significant O-alkylation. Moreover, the reaction of trimethylsilyl derivatives of N(6)-acetyl-2',3',5'-tri-O-acetyladenosine and N(6)-acetyl-3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides leads to the formation of the stable 1-N-substituted adenosines. Dimroth rearrangement of 1-N-substituted adenosines in aqueous ammonia yields pure N(6)-substituted adenosines.

Molecular printboards as a general platform for protein immobilization: A supramolecular solution to nonspecific adsorption

NARCIS (Netherlands)

Ludden, M.J.W.; Mulder, A.; Tampe, Robert; Reinhoudt, David; Huskens, Jurriaan

2007-01-01

Be specific: A supramolecular adsorbate consisting of an adamantyl group (red) and an oligo(ethylene glycol) chain has been designed to prevent nonspecific protein adsorption at cyclodextrin molecular printboards. The adamantyl group allows specific and reversible interactions. Specific

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

Science.gov (United States)

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

2017-12-01

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

Epistasis increases the rate of conditionally neutral substitution in an adapting population.

Science.gov (United States)

Draghi, Jeremy A; Parsons, Todd L; Plotkin, Joshua B

2011-04-01

Kimura observed that the rate of neutral substitution should equal the neutral mutation rate. This classic result is central to our understanding of molecular evolution, and it continues to influence phylogenetics, genomics, and the interpretation of evolution experiments. By demonstrating that neutral mutations substitute at a rate independent of population size and selection at linked sites, Kimura provided an influential justification for the idea of a molecular clock and emphasized the importance of genetic drift in shaping molecular evolution. But when epistasis among sites is common, as numerous empirical studies suggest, do neutral mutations substitute according to Kimura's expectation? Here we study simulated, asexual populations of RNA molecules, and we observe that conditionally neutral mutations--i.e., mutations that do not alter the fitness of the individual in which they arise, but that may alter the fitness effects of subsequent mutations--substitute much more often than expected while a population is adapting. We quantify these effects using a simple population-genetic model that elucidates how the substitution rate at conditionally neutral sites depends on the population size, mutation rate, strength of selection, and prevalence of epistasis. We discuss the implications of these results for our understanding of the molecular clock, and for the interpretation of molecular variation in laboratory and natural populations.

Azomethines, isoxazole, N-substituted pyrazoles and pyrimidine containing curcumin derivatives: Urease inhibition and molecular modeling studies.

Science.gov (United States)

Ahmed, Mahmood; Qadir, Muhammad Abdul; Hameed, Abdul; Arshad, Muhammad Nadeem; Asiri, Abdullah M; Muddassar, Muhammad

2017-08-19

Curcumin has shown large number of pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its various derivatives for diverse biological functions. In this study, curcumin derived azomethine, isoxazole, pyrimidines and N-substituted pyrazoles were synthesized to investigate their urease enzyme inhibition. The structures of newly synthesized compounds were described by IR, MS, 1 H NMR and 13 C NMR spectral data. Urease enzyme inhibition was evaluated through in vitro assays in which compound 8b was found to be the most potent (IC 50  = 2.44 ± 0.07 μM) among the tested compounds. The compounds with diazine ring system except the 4d showed better urease inhibition (IC 50  = 11.43 ± 0.21-19.63 ± 0.28 μM) than the standard urease inhibitor thiourea (IC 50  = 22.61 ± 0.23 μM). Similarly enzyme kinetics data revealed that compounds 3c-3e and 8b were competitive inhibitors with Ki values of 20.0, 19.87, 20.23 and 19.11 μM respectively while the compounds 4b, 4c and 4e were mixed type of inhibitors with Ki values 6.72, 19.69 and 6.72 μM respectively. Molecular docking studies were also performed to identify the plausible binding modes of the most active compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

Photodegradation of malachite green dye catalyzed by Keggin-type polyoxometalates under visible-light irradiation: Transition metal substituted effects

Science.gov (United States)

Liu, Chun-Guang; Zheng, Ting; Liu, Shuang; Zhang, Han-Yu

2016-04-01

In the present paper, Keggin-type polyoxometalates (POMs) (NH4)3[PW12O40] and its mono-transition-metal-substituted species (NH4)5[{PW11O39}MII(H2O)] (M = Mn, Fe, Co, Ni, Cu, Zn) have been synthesized and used as photocatalyst to activate O2 for the degradation of dye molecule under visible-light irradiation. Because of the strong adsorption on the surface of POM catalyst, malachite green (MG) molecule was employed as a molecular probe to test their photocatalytic activity. The photodegradation study shows that introduction of transition metal ion leads to an increase in the degradation of MG in the following order: Mn < Fe < Co < [PW12O40]3- < Ni < Cu < Zn, which indicates that the photocatalytic activity of these POMs is sensitive to the transition metal substituted effects. Electronic structure analysis based on the density functional theory calculations shows that a moderate decrease of oxidizing ability of POM catalyst may improve the photocatalytic activity in the degradation of dye molecule under visible-light irradiation. Meanwhile, intermediate products about the photocatalytic oxidation of MG molecule were proposed on the basis of gas chromatograph mass spectrometer analysis.

Trypanocidal 1,3-arylene diketone bis(guanylhydrazone)s. Structure-activity relationships among substituted and heterocyclic analogues.

Science.gov (United States)

Ulrich, P; Cerami, A

1984-01-01

Based on the antitrypanosomal activity of 1,3-diacetylbenzene bis(guanylhydrazone) (4) and 2,6-diacetylpyridine bis(guanylhydrazone) (17), a number of substituted and heterocyclic 1,3-arylene diketone bis(guanylhydrazone)s were prepared and tested against Trypanosoma brucei infections in mice. A wide range of ED50 values was observed among 5-substituted derivatives of 4. The 5-amino analogue 5 and 5-acetamido analogue 6 were about twice as active as 4. 1,3,5-Triacetylbenzene tris(guanylhydrazone) (12) was about 9 times as active as 4 and was approximately one-half as active as the currently used trypanocide diminazene aceturate in this test system. Other 5-derivatives had activity equivalent to or less than that of the parent compound 4. Three new heterocyclic analogues were all less active than 2,6-diacetylpyridine derivative 17 and benzene derivative 4. Ring substitution ortho to the guanylhydrazone side chains was invariably detrimental to activity. Side-chain homologues 1,3-dipentanoylbenzene bis(guanylhydrazone) and 1,3-diacetylbenzene bis(2-imidazolin-2-ylhydrazone) were essentially inactive.

Template-Assisted Benzannulation Route to Pentacene and Tetracene Derivatives and its Application to Construct Amphiphilic Acenes That Self-Assemble into Helical Wires.

Science.gov (United States)

Pal, Bikash; Chang, Chun-Hsiung; Zeng, Cian-Jhe; Lin, Chih-Hsiu

2017-12-11

Pentacene is one of the most versatile organic semiconductors. New synthetic strategies to construct the pentacene skeleton are imperative to produce pentacene derivatives with appropriate solubility, stability, and optoelectronic properties for various applications. This paper describes a template-directed approach to pentacene derivatives. In the retrosynthesis, the acene skeleton is viewed as a laddered double strand polyene instead of the more intuitive linearly fused hexagons. Based on this vision, the template strand of polyene is constructed with Wittig olefination, whereas the second strand is accomplished with Knoevenagel condensation to produce pentacene and tetracene derivatives. The synthetic scheme is flexible enough to generate an array of acene derivatives with substitution patterns that were hitherto difficult to access. Amphiphilic pentacene and tetracene derivatives were also synthesized by the template strategy. One pentacene based amphiphilic rod-coil molecule undergoes self-assembly to form helical wire structures that were visualized with TEM. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Activity of cationically substituted bis-benzimidazoles against experimental Pneumocystis carinii pneumonia.

Science.gov (United States)

Tidwell, R R; Jones, S K; Naiman, N A; Berger, L C; Brake, W B; Dykstra, C C; Hall, J E

1993-01-01

On the basis of a previously observed correlation between the antimicrobial activity and DNA binding strength of dicationic molecules, a series of 10 dicationically substituted bis-benzimidazoles were tested for activity in the rat model of Pneumocystis carinii pneumonia. One of the compounds, 1,4-bis[5-(2-imidazolinyl)-2-benzimidazolyl]butane, was found to be more potent and less toxic than pentamidine. PMID:8215291

Global chaos synchronization of electro-mechanical gyrostat systems via variable substitution control

International Nuclear Information System (INIS)

Chen Yun; Wu Xiaofeng; Liu Zhong

2009-01-01

This paper studies global synchronization of non-autonomous chaotic electro-mechanical gyrostat systems via variable substitution control. A master-slave non-autonomous synchronization scheme with variable substitution control is mathematically presented. Based on the scheme, some sufficient algebraic criteria for global chaos synchronization of master and slave electro-mechanical gyrostat systems via various single-variable coupling are derived. The effectiveness of the obtained criteria is numerically illustrated by the examples.

Retinoid X Receptor α-Dependent HBV Minichromosome Remodeling and Viral Replication.

Science.gov (United States)

Zhang, Yan; He, Song; Guo, Jin-Jun; Peng, Hong; Fan, Jia-Hao; Li, Qing-Ling

2017-01-01

The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor α (RXRα), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. This study investigated RXRα involvement in HBV cccDNA epigenetic modifications. Quantitative cccDNA chromatin immunoprecipitation (ChIP) was applied to study the recruitment of RXRα, histones, and chromatin-modifying enzymes to HBV minichromosome in HepG2 cells after transfection of the linear HBV genome. RXRα Was found to directly bind to HBV cccDNA; recruitment of RXRα to HBV mini-chromosome paralleled HBV replication, histone recruitment, and histone acetylation in HBVcccDNA. Moreover, RXRα overexpression or knock-down significantly increased or impaired the recruitment of the p300 acetyltransferase to cccDNAminichromosome. Our results confirmed the regulation of RXRα on HBV replication in vitro and demonstrated the modulation of RXRα on HBV cccDNA epigenetics. These findings provide a profound theoretical and experimental basis for late-model antiviral treatment acting on the HBV cccDNA and minichromosome.

Synthesis and Antidepressant Activity of Some New 5-(1H-Indol-3-yl-3-(substituted aryl-4,5-dihydroisoxazoline Derivatives

Directory of Open Access Journals (Sweden)

Pravin O. Patil

2013-01-01

Full Text Available The present study refers to the synthesis of new antidepressant candidates using the indole scaffold. In an attempt to identify potential lead antidepressant agents, a number of indole molecules, incorporating isoxazoline, were synthesized by microwave-assisted synthesis. The antidepressant activity of the synthesized compounds (3a–3n was evaluated by forced swim test in mice and their locomotor activity was assessed using actophotometry. The present paper showed significant antidepressant activity for all compounds of the series and no significant change in locomotor activity of mice. Compounds 3d and 3j were found to be potent molecules of this series, when compared with the reference drugs imipramine and fluoxetine. It clearly demonstrated that replacement of aromatic core by appropriate heterocycles such as pyridine and pyrrole on the 5-(1H-Indol-3-yl-3-(Phenyl-4,5-dihydroisoxazoline (3a would generate more potent derivatives. Thus, these compounds can serve as potential leads for further antidepressant studies.

In Silico Screening, Synthesis and In Vitro Evaluation of Some Quinazolinone and Pyridine Derivatives as Dihydrofolate Reductase Inhibitors for Anticancer Activity

Directory of Open Access Journals (Sweden)

A. G. Nerkar

2009-01-01

Full Text Available Dihydrofolate reductase (DHFR is the important target for anticancer drugs belonging to the class of antimetabolites as the enzyme plays important role in the de novo purine synthesis. We here report the in silico screening to obtain best fit molecules as DHFR inhibitors, synthesis of some ʻbest fitʼ quinazolinone from 2-phenyl-3-(substituted-benzilidine-amino quinazolinones (Quinazolinone Shiff's bases QSB1-5 and pyridine-4-carbohydrazide Shiff's bases (ISB1-5 derivatives and their in vitro anticancer assay. Synthesis of the molecules was performed using microwave assisted synthesis. The structures of these molecules were elucidated by IR and 1H-NMR. These compounds were then subjected for in vitro anticancer evaluation against five human cancer cell-lines for anticancer cyto-toxicity assay. Methotrexate (MTX was used as standard for this evaluation to give a comparable inhibition of the cell proliferation by DHFR inhibition. Placlitaxel, adriamycin and 5-fluoro-uracil were also used as standard to give a comparable activity of these compounds with other mechanism of anticancer activity. ISB3 (4-(N, N-dimethyl-amino-phenyl Schiff''s base derivative of pyridine carbohydrazide showed equipotent activity with the standards used in in vitro anticancer assay as per the NCI (National Cancer Institute guidelines.

Agrobacterium tumefaciens responses to plant-derived signaling molecules

Science.gov (United States)

Subramoni, Sujatha; Nathoo, Naeem; Klimov, Eugene; Yuan, Ze-Chun

2014-01-01

As a special phytopathogen, Agrobacterium tumefaciens infects a wide range of plant hosts and causes plant tumors also known as crown galls. The complexity of Agrobacterium–plant interaction has been studied for several decades. Agrobacterium pathogenicity is largely attributed to its evolved capabilities of precise recognition and response to plant-derived chemical signals. Agrobacterium perceives plant-derived signals to activate its virulence genes, which are responsible for transferring and integrating its Transferred DNA (T-DNA) from its Tumor-inducing (Ti) plasmid into the plant nucleus. The expression of T-DNA in plant hosts leads to the production of a large amount of indole-3-acetic acid (IAA), cytokinin (CK), and opines. IAA and CK stimulate plant growth, resulting in tumor formation. Agrobacterium utilizes opines as nutrient sources as well as signals in order to activate its quorum sensing (QS) to further promote virulence and opine metabolism. Intriguingly, Agrobacterium also recognizes plant-derived signals including γ-amino butyric acid and salicylic acid (SA) to activate quorum quenching that reduces the level of QS signals, thereby avoiding the elicitation of plant defense and preserving energy. In addition, Agrobacterium hijacks plant-derived signals including SA, IAA, and ethylene to down-regulate its virulence genes located on the Ti plasmid. Moreover, certain metabolites from corn (Zea mays) also inhibit the expression of Agrobacterium virulence genes. Here we outline the responses of Agrobacterium to major plant-derived signals that impact Agrobacterium–plant interactions. PMID:25071805

Agrobacterium tumefaciens responses to plant-derived signaling molecules

Directory of Open Access Journals (Sweden)

Sujatha eSubramoni

2014-07-01

Full Text Available As a special phytopathogen, Agrobacterium tumefaciens infects a wide range of plant hosts and causes plant tumors also known as crown galls. The complexity of Agrobacterium-plant interaction has been studied for several decades. Agrobacterium pathogenicity is largely attributed to its evolved capabilities of precise recognition and response to plant-derived chemical signals. Agrobacterium perceives plant-derived signals to activate its virulence genes, which are responsible for transferring and integrating its T-DNA (Transferred DNA from its Tumour-inducing (Ti plasmid into the plant nucleus. The expression of T-DNA in plant hosts leads to the production of a large amount of indole-3-acetic acid (IAA, cytokinin (CK and opines. IAA and CK stimulate plant growth, resulting in tumor formation. Agrobacterium utilizes opines as nutrient sources as well as signals in order to activate its quorum sensing (QS to further promote virulence and opine metabolism. Intriguingly, Agrobacterium also recognizes plant-derived signals including -amino butyric acid (GABA and salicylic acid (SA to activate quorum quenching that reduces the level of QS signals, thereby avoiding the elicitation of plant defense and preserving energy. In addition, Agrobacterium hijacks plant-derived signals including SA, IAA, and ethylene (ET to down-regulate its virulence genes located on the Ti plasmid. Moreover, certain metabolites from corn (Zea mays also inhibit the expression of Agrobacterium virulence genes. Here we outline the responses of Agrobacterium to major plant-derived signals that impact Agrobacterium-plant interactions.

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)-.

Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity

OpenAIRE

Bavik, Claes; Henry, Susan Hayes; Zhang, Yan; Mitts, Kyoko; McGinn, Tim; Budzynski, Ewa; Pashko, Andriy; Lieu, Kuo Lee; Zhong, Sheng; Blumberg, Bruce; Kuksa, Vladimir; Orme, Mark; Scott, Ian; Fawzi, Ahmad; Kubota, Ryo

2015-01-01

© 2015 Bavik et al. Increased exposure to blue or visible light, fluctuations in oxygen tension, and the excessive accumulation of toxic retinoid byproducts places a tremendous amount of stress on the retina. Reduction of visual chromophore biosynthesis may be an effective method to reduce the impact of these stressors and preserve retinal integrity. A class of non-retinoid, small molecule compounds that target key proteins of the visual cycle have been developed. The first candidate in this ...

Exciplex electroluminescence and photoluminescence spectra of the new organic materials based on zinc complexes of sulphanylamino-substituted ligands.

Science.gov (United States)

Kaplunov, Mikhail G; Krasnikova, Svetlana S; Nikitenko, Sergey L; Sermakasheva, Natalia L; Yakushchenko, Igor K

2012-04-03

We have investigated the electroluminescence spectra of the electroluminescent devices based on the new zinc complexes of amino-substituted benzothiazoles and quinolines containing the C-N-M-N chains in their chelate cycles. The spectra exhibit strong exciplex bands in the green to yellow region 540 to 590 nm due to interaction of the excited states of zinc complexes and triaryl molecules of the hole-transporting layer. For some devices, the intrinsic luminescence band of 460 nm in the blue region is also observed along with the exciplex band giving rise to an almost white color of the device emission. The exciplex band can be eliminated if the material of the hole-transporting layer is not a triarylamine derivative. We have also found the exciplex emission in the photoluminescence spectra of the films containing blends of zinc complex and triphenylamine material.

Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

International Nuclear Information System (INIS)

Defo, Michel A.; Bernatchez, Louis; Campbell, Peter G.C.; Couture, Patrice

2014-01-01

Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

Waterborne cadmium and nickel impact oxidative stress responses and retinoid metabolism in yellow perch

Energy Technology Data Exchange (ETDEWEB)

Defo, Michel A. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Bernatchez, Louis [Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, Québec G1V 0A6 (Canada); Campbell, Peter G.C. [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada); Couture, Patrice, E-mail: patrice.couture@ete.inrs.ca [Institut national de la recherche scientifique (INRS), Centre Eau Terre Environnement, 490 de la Couronne, Québec, Québec G1K 9A9 (Canada)

2014-09-15

Highlights: • Cd and Ni affected indicators of retinoid metabolism and oxidative stress in fish. • Liver rdh-2 transcription levels increase in fish exposed to waterborne Cd. • Liver REH and LdRAT activities increase with increasing kidney Cd concentration. • Changes at molecular levels do not always mean changes at the functional levels. • Multi-level biological approaches are needed when assessing fish metal toxicology. - Abstract: In this experiment, we studied the transcriptional and functional (enzymatic) responses of yellow perch (Perca flavescens) to metal stress, with a focus on oxidative stress and vitamin A metabolism. Juvenile yellow perch were exposed to two environmentally relevant concentrations of waterborne cadmium (Cd) and nickel (Ni) for a period of 6 weeks. Kidney Cd and Ni bioaccumulation significantly increased with increasing metal exposure. The major retinoid metabolites analyzed in liver and muscle decreased with metal exposure except at high Cd exposure where no variation was reported in liver. A decrease in free plasma dehydroretinol was also observed with metal exposure. In the liver of Cd-exposed fish, both epidermal retinol dehydrogenase 2 transcription level and corresponding enzyme activities retinyl ester hydrolase and lecithin dehydroretinyl acyl transferase increased. In contrast, muscle epidermal retinol dehydrogenase 2 transcription level decreased with Cd exposure. Among antioxidant defences, liver transcription levels of catalase, microsomal glutathione-S-transferase-3 and glucose-6-phosphate dehydrogenase were generally enhanced in Cd-exposed fish and this up-regulation was accompanied by an increase in the activities of corresponding enzymes, except for microsomal glutathione-S-transferase. No consistent pattern in antioxidant defence responses was observed between molecular and biochemical response when fish were exposed to Ni, suggesting a non-synchronous response of antioxidant defence in fish exposed to

Benzo[1,2-b:4,5-b’]dithiophene-Pyrido[3,4-b]pyrazine Small-Molecule Donors for Bulk Heterojunction Solar Cells

KAUST Repository

Wolf, Jannic Sebastian; Babics, Maxime; Wang, Kai; Saleem, Qasim; Liang, Ru-Ze; Hansen, Michael Ryan; Beaujuge, Pierre

2016-01-01

We report on the synthesis, material properties and BHJ solar cell characteristics of a set of π-conjugated small-molecule (SM) donors composed of benzo[1,2-b:4,5-b′]dithiophene (BDT) and pyrido[3,4-b]pyrazine (PP) units – examining the perspectives of alkyl-substituted PP acceptor motifs in SM designs. In these systems (SM1-4), both the type of side chains derived from the PP motifs and the presence of ring-substituents on BDT critically impact (i) molecular packing, and (ii) thin-film morphologies and charge transport in BHJ solar cells. With the appropriate side-chain pattern, the ring-substituted analogue SM4 stands out: achieving efficiencies of ca. 6.5% with PC71BM, and fine-scale morphologies comparable to those obtained with some of the best-performing polymer donors in BHJ solar cells. 1H-1H DQ-SQ NMR analyses are used to examine the distinct self-assembly pattern of SM4, expected to factor into the development of the BHJ morphology.

Benzo[1,2-b:4,5-b’]dithiophene-Pyrido[3,4-b]pyrazine Small-Molecule Donors for Bulk Heterojunction Solar Cells

KAUST Repository

Wolf, Jannic Sebastian

2016-01-22

We report on the synthesis, material properties and BHJ solar cell characteristics of a set of π-conjugated small-molecule (SM) donors composed of benzo[1,2-b:4,5-b′]dithiophene (BDT) and pyrido[3,4-b]pyrazine (PP) units – examining the perspectives of alkyl-substituted PP acceptor motifs in SM designs. In these systems (SM1-4), both the type of side chains derived from the PP motifs and the presence of ring-substituents on BDT critically impact (i) molecular packing, and (ii) thin-film morphologies and charge transport in BHJ solar cells. With the appropriate side-chain pattern, the ring-substituted analogue SM4 stands out: achieving efficiencies of ca. 6.5% with PC71BM, and fine-scale morphologies comparable to those obtained with some of the best-performing polymer donors in BHJ solar cells. 1H-1H DQ-SQ NMR analyses are used to examine the distinct self-assembly pattern of SM4, expected to factor into the development of the BHJ morphology.

Focal epithelial hyperplasia by human papillomavirus (HPV)-32 misdiagnosed as HPV-16 and treated with combination of retinoids, imiquimod and quadrivalent HPV vaccine.

Science.gov (United States)

Gemigniani, Franco; Hernández-Losa, Javier; Ferrer, Berta; García-Patos, Vicente

2015-12-01

Focal epithelial hyperplasia (FEH) or Heck's disease is a rare, benign and asymptomatic mucosal proliferation associated with human papillomavirus (HPV) infection, mainly with genotypes 13 and 32. We report a florid case of FEH in an 11-year-old Haitian girl with systemic lupus erythematosus receiving immunosuppressive therapy. Cryotherapy was previously performed on numerous occasions with no results. We decided to prescribe a non-invasive and more comfortable treatment. A combination of topical retinoid and imiquimod cream was well tolerated and led to an important improvement. The evidence of infection by HPV-16 detected by polymerase chain reaction (PCR) technique, prompted us to prescribe the quadrivalent HPV vaccine (types 6, 11,16 and 18). Subsequent PCR sequencing with generic primers GP5-GP6 and further BLAST comparative analysis confirmed that genomic viral sequence in our case truly corresponded with HPV-32. This molecular misdiagnosis can be explained by the similarity between genomic sequences of both HPV-16 and -32 genotypes. At the 1-year follow up, we observed total clinical improvement and no recurrences of the disease. Complete healing in this case may correspond to a potential action of topical retinoid, imiquimod and the cross-protection mechanism of the quadrivalent HPV vaccine. © 2015 Japanese Dermatological Association.

Three-dimensional model of a selective theophylline-binding RNA molecule

Energy Technology Data Exchange (ETDEWEB)

Tung, Chang-Shung; Oprea, T.I.; Hummer, G.; Garcia, A.E.

1995-07-01

We propose a three-dimensional (3D) model for an RNA molecule that selectively binds theophylline but not caffeine. This RNA, which was found using SELEX [Jenison, R.D., et al., Science (1994) 263:1425] is 10,000 times more specific for theophylline (Kd=320 nM) than for caffeine (Kd=3.5 mM), although the two ligands are identical except for a methyl group substituted at N7 (present only in caffeine). The binding affinity for ten xanthine-based ligands was used to derive a Comparative Molecular Field Analysis (CoMFA) model (R{sup 2} = 0.93 for 3 components, with cross-validated R{sup 2} of 0.73), using the SYBYL and GOLPE programs. A pharmacophoric map was generated to locate steric and electrostatic interactions between theophylline and the RNA binding site. This information was used to identify putative functional groups of the binding pocket and to generate distance constraints. Based on a model for the secondary structure (Jenison et al., idem), the 3D structure of this RNA was then generated using the following method: each helical region of the RNA molecule was treated as a rigid body; single-stranded loops with specific end-to-end distances were generated. The structures of RNA-xanthine complexes were studied using a modified Monte Carlo algorithm. The detailed structure of an RNA-ligand complex model, as well as possible explanations for the theophylline selectivity will be discussed.

Electric moments in molecule interferometry

International Nuclear Information System (INIS)

Eibenberger, Sandra; Gerlich, Stefan; Arndt, Markus; Tuexen, Jens; Mayor, Marcel

2011-01-01

We investigate the influence of different electric moments on the shift and dephasing of molecules in a matter wave interferometer. Firstly, we provide a quantitative comparison of two molecules that are non-polar yet polarizable in their thermal ground state and that differ in their stiffness and response to thermal excitations. While C 25 H 20 is rather rigid, its larger derivative C 49 H 16 F 52 is additionally equipped with floppy side chains and vibrationally activated dipole moment variations. Secondly, we elucidate the role of a permanent electric dipole momentby contrasting the quantum interference pattern of a (nearly) non-polar and a polar porphyrin derivative. We find that a high molecular polarizability and even sizeable dipole moment fluctuations are still well compatible with high-contrast quantum interference fringes. The presence of permanent electric dipole moments, however, can lead to a dephasing and rapid degradation of the quantum fringe pattern already at moderate electric fields. This finding is of high relevance for coherence experiments with large organic molecules, which are generally equipped with strong electric moments.

New dendrimer - peptide host - guest complexes : towards dendrimers as peptide carriers

NARCIS (Netherlands)

Boas, U.; Sontjens, S.H.M.; Jensen, K.J.; Christensen, J.B.; Meijer, E.W.

2002-01-01

Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions

Independent Activation of Hepatitis B Virus Biosynthesis by Retinoids, Peroxisome Proliferators, and Bile Acids

Science.gov (United States)

Reese, Vanessa C.; Oropeza, Claudia E.

2013-01-01

In the human hepatoma cell line HepG2, retinoic acid, clofibric acid, and bile acid treatment can only modestly increase hepatitis B virus (HBV) biosynthesis. Utilizing the human embryonic kidney cell line 293T, it was possible to demonstrate that the retinoid X receptor α (RXRα) plus its ligand can support viral biosynthesis independently of additional nuclear receptors. In addition, RXRα/peroxisome proliferator-activated receptor α (PPARα) and RXRα/farnesoid X receptor α (FXRα) heterodimeric nuclear receptors can also mediate ligand-dependent HBV transcription and replication when activated by clofibric acid and bile acid, respectively, independently of a requirement for the ligand-dependent activation of RXRα. These observations indicate that there are at least three possible modes of ligand-mediated activation of HBV transcription and replication existing within hepatocytes, suggesting that multiple independent mechanisms control viral production in the livers of infected individuals. PMID:23135717

Synthesis, characterization and screening for antidepressant and anticonvulsant activity of 4,5-dihydropyrazole bearing indole derivatives

Directory of Open Access Journals (Sweden)

Pravin O. Patil

2016-07-01

Full Text Available In the present study, a series of new substituted 5-(1H-Indol-3-yl-3-(phenyl-4,5-dihydropyrazoline derivatives (2a–m have been synthesized with good yield by microwave assisted synthesis. The compounds synthesized were screened for antidepressant and anticonvulsant potentialities in mice by a forced swim test and subcutaneous pentylenetetrazole (scPTZ test, respectively. Neuro-toxicities were determined by rotarod test in albino mice. The structures of all new compounds were confirmed by IR, 1H NMR, mass spectral data, and microanalyses. The results revealed that compounds 2b, 2e and 2k were found to be potent antidepressant molecules of the series, at 20 mg/kg dose level when compared with the reference drugs imipramine and fluoxetine. Whereas, compounds 2c and 2d were found to be potent anticonvulsant molecules of this series, when compared with the reference drug diazepam. None of the synthesized compounds showed neurotoxicity.

Synthesis and Electroluminescence Properties of 3-(Trifluoromethylphenyl-Substituted 9,10-Diarylanthracene Derivatives for Blue Organic Light-Emitting Diodes

Directory of Open Access Journals (Sweden)

Sang Woo Kwak

2017-10-01

Full Text Available Diaryl-substituted anthracene derivatives containing 3-(trifluoromethylphenyl groups, 9,10-diphenyl-2-(3-(trifluoromethylphenylanthracene (1, 9,10-di([1,1′-biphenyl]-4-yl-2-(3-(trifluoromethylphenylanthracene (2, and 9,10-di(naphthalen-2-yl-2-(3-(trifluoromethylphenylanthracene (3 were synthesized and characterized. The compounds 1–3 possessed high thermal stability and proper frontier-energy levels, which make them suitable as host materials for blue organic light-emitting diodes. The electroluminescent (EL emission maximum of the three N,N-diphenylamino phenyl vinyl biphenyl (DPAVBi-doped (8 wt % devices for compounds 1–3 was exhibited at 488 nm (for 1 and 512 nm (for 2 and 3. Among them, the 1-based device displayed the highest device performances in terms of brightness (Lmax = 2153.5 cd·m−2, current efficiency (2.1 cd·A−1, and external quantum efficiency (0.8%, compared to the 2- and 3-based devices.

Biologic and clinical aspects of integration of different bone substitutes in oral surgery: a literature review.

Science.gov (United States)

Zizzari, Vincenzo Luca; Zara, Susi; Tetè, Giulia; Vinci, Raffaele; Gherlone, Enrico; Cataldi, Amelia

2016-10-01

Many bone substitutes have been proposed for bone regeneration, and researchers have focused on the interactions occurring between grafts and host tissue, as the biologic response of host tissue is related to the origin of the biomaterial. Bone substitutes used in oral and maxillofacial surgery could be categorized according to their biologic origin and source as autologous bone graft when obtained from the same individual receiving the graft; homologous bone graft, or allograft, when harvested from an individual other than the one receiving the graft; animal-derived heterologous bone graft, or xenograft, when derived from a species other than human; and alloplastic graft, made of bone substitute of synthetic origin. The aim of this review is to describe the most commonly used bone substitutes, according to their origin, and to focus on the biologic events that ultimately lead to the integration of a biomaterial with the host tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

One-step synthesis of an {sup 18}F-labeled boron-derived methionine analog. A substitute for {sup 11}C-methionine?

Energy Technology Data Exchange (ETDEWEB)

Liu, Zhen; Lan, Xiaoli [Huazhong University of Science and Technology, Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Wuhan (China); Huazhong University of Science and Technology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Wuhan (China); Ehlerding, Emily B. [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); Cai, Weibo [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin - Madison, Carbone Cancer Center, Madison, WI (United States)

2018-04-15

Amino acid-based tracers have been extensively investigated for positron emission tomography (PET) imaging of brain tumors, and {sup 11}C-methionine ({sup 11}C-MET) is one of the most extensively investigated. However, widespread clinical use of {sup 11}C-MET is challenging due to the short half-life of {sup 11}C and low radiolabeling yield. In this issue of the European Journal of Nuclear Medicine and Molecular Imaging, Yang and colleagues report an {sup 18}F-labeled boron-derived methionine analog, {sup 18}F-B-MET, as a potential substitute for {sup 11}C-MET in PET imaging of glioma. The push-button synthesis, highly efficient radiolabeling, and good imaging performance in glioma models make this tracer a promising candidate for future clinical translation. (orig.)

CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice

Directory of Open Access Journals (Sweden)

Tomasz Maj

2014-01-01

Full Text Available Immune phenomena during the preimplantation period of pregnancy are poorly understood. The aim of our study was to assess the capacity for antigen presentation of splenic antigen-presenting cells (APCs derived from pregnant and pseudopregnant mice in in vitro conditions. Therefore, sorted CD11c+ dendritic cells and macrophages F4/80+ and CD11b+ presenting ovalbumin (OVA were cocultured with CD4+ T cells derived from OT-II mice’s (C57BL6/J-Tg(TcraTcrb1100Mjb/J spleen. After 132 hours of cell culture, proliferation of lymphocytes (ELISA-BrdU, activation of these cells (flow cytometry, cytokine profile (ELISA, and influence of costimulatory molecules blocking on these parameters were measured. We did not detect any differences in regulation of Th1/Th2 cytokine balance. CD86 seems to be the main costimulatory molecule involved in the proliferation response but CD80 is the main costimulatory molecule influencing cytokine secretion in pregnant mice. In conclusion, this study showed that CD80 and CD86 costimulatory molecules regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. The implications of these changes still remain unclear.

Interaction of an immunodominant epitope with Ia molecules in T-cell activation

DEFF Research Database (Denmark)

Adorini, L; Sette, A; Buus, S

1988-01-01

The amino acid sequence corresponding to residues 107-116 of hen egg-white lysozyme (HEL) has been identified as containing an immunodominant T-cell epitope recognized in association with the I-Ed molecule. The immunodominance of this epitope in HEL-primed H-2d mice was demonstrated by analysis o......-120)-peptide was found to be immunogenic in H-2d mice. Thus, a single semiconservative substitution drastically reduces binding capacity and abolishes immunogenicity, suggesting that a strict correlation exists between binding of a peptide to Ia molecules and its immunogenicity....

1,3- and 1,4-Substituted tetrazolium salts

International Nuclear Information System (INIS)

Voitekhovich, Sergei V; Gaponik, Pavel N; Ivashkevich, Oleg A

2002-01-01

The published data on the synthesis, physicochemical properties, structures and reactions of 1,3-(1,3,5)- and 1,4-(1,4,5)-substituted tetrazolium salts are systematised and generalised. Their applications as starting compounds in the preparative chemistry of heterocyclic derivatives and some other branches of science and technology are reviewed. The bibliography includes 122 references.

Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

Science.gov (United States)

Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

2017-01-01

Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

Rheological and structural studies of carboxymethyl derivatives of chitosan

Science.gov (United States)

Winstead, Cherese; Katagumpola, Pushpika

2014-05-01

The degrees of substitution of chitosan derivatives were varied and the viscoelastic behavior of these biopolymer solutions was studied using rheology. Chitosan is a cationic copolymer of glucosamine and N-acetylglucosamine obtained by alkaline deacetylation of chitin. Due to its inherent non-toxicity, biocompatibility, and biodegradability, chitosan has gained much interest. However, the poor solubility of the biopolymer in water and most common organic solvents limits its applications. Therefore, the focus of this work is the chemical modification of chitosan via carboxymethylation as well as studying the viscoelastic behavior of these polymer solutions. Varying degrees of substitution (DS) of carboxymethyl chitosan derivatives were synthesized by treating chitosan with monochloroacetic acid under alkylated medium varying the reaction time and temperature. The effect of degree of substitution on the rheology of these polymer solutions was studied as a function of concentration. The viscosity of chitosan derivatives sharply increased with increase in degree of substitution. G' and G" dependence on strain and angular frequency were studied and were found to exhibit predominantly viscous behavior. Additional characterization of the derivatized products were further studied using Fourier transform infrared (FT-IR), 1H Nuclear Magnetic Resonance (1H NMR) spectroscopy, X-ray diffraction (XRD), and thermal gravimetric analysis as well as differential scanning calorimetry (DSC). Degree of substitution (DS) was calculated by titrimetric method.

Rheological and structural studies of carboxymethyl derivatives of chitosan

International Nuclear Information System (INIS)

Winstead, Cherese; Katagumpola, Pushpika

2014-01-01

The degrees of substitution of chitosan derivatives were varied and the viscoelastic behavior of these biopolymer solutions was studied using rheology. Chitosan is a cationic copolymer of glucosamine and N-acetylglucosamine obtained by alkaline deacetylation of chitin. Due to its inherent non-toxicity, biocompatibility, and biodegradability, chitosan has gained much interest. However, the poor solubility of the biopolymer in water and most common organic solvents limits its applications. Therefore, the focus of this work is the chemical modification of chitosan via carboxymethylation as well as studying the viscoelastic behavior of these polymer solutions. Varying degrees of substitution (DS) of carboxymethyl chitosan derivatives were synthesized by treating chitosan with monochloroacetic acid under alkylated medium varying the reaction time and temperature. The effect of degree of substitution on the rheology of these polymer solutions was studied as a function of concentration. The viscosity of chitosan derivatives sharply increased with increase in degree of substitution. G' and G' dependence on strain and angular frequency were studied and were found to exhibit predominantly viscous behavior. Additional characterization of the derivatized products were further studied using Fourier transform infrared (FT-IR), 1 H Nuclear Magnetic Resonance ( 1 H NMR) spectroscopy, X-ray diffraction (XRD), and thermal gravimetric analysis as well as differential scanning calorimetry (DSC). Degree of substitution (DS) was calculated by titrimetric method

Single-molecule stochastic times in a reversible bimolecular reaction

Science.gov (United States)

Keller, Peter; Valleriani, Angelo

2012-08-01

In this work, we consider the reversible reaction between reactants of species A and B to form the product C. We consider this reaction as a prototype of many pseudobiomolecular reactions in biology, such as for instance molecular motors. We derive the exact probability density for the stochastic waiting time that a molecule of species A needs until the reaction with a molecule of species B takes place. We perform this computation taking fully into account the stochastic fluctuations in the number of molecules of species B. We show that at low numbers of participating molecules, the exact probability density differs from the exponential density derived by assuming the law of mass action. Finally, we discuss the condition of detailed balance in the exact stochastic and in the approximate treatment.

Upgrading Lignocellulosic Biomasses: Hydrogenolysis of Platform Derived Molecules Promoted by Heterogeneous Pd-Fe Catalysts

Directory of Open Access Journals (Sweden)

Claudia Espro

2017-03-01

Full Text Available This review provides an overview of heterogeneous bimetallic Pd-Fe catalysts in the C–C and C–O cleavage of platform molecules such as C2–C6 polyols, furfural, phenol derivatives and aromatic ethers that are all easily obtainable from renewable cellulose, hemicellulose and lignin (the major components of lignocellulosic biomasses. The interaction between palladium and iron affords bimetallic Pd-Fe sites (ensemble or alloy that were found to be very active in several sustainable reactions including hydrogenolysis, catalytic transfer hydrogenolysis (CTH and aqueous phase reforming (APR that will be highlighted. This contribution concentrates also on the different synthetic strategies (incipient wetness impregnation, deposition-precipitaion, co-precipitaion adopted for the preparation of heterogeneous Pd-Fe systems as well as on the main characterization techniques used (XRD, TEM, H2-TPR, XPS and EXAFS in order to elucidate the key factors that influence the unique catalytic performances observed.

Organized single-molecule magnets: direct observation of new Mn12 derivatives on gold

International Nuclear Information System (INIS)

Cornia, A.; Fabretti, A.C.; Pacchioni, M.; Zobbi, L.; Bonacchi, D.; Caneschi, A.; Gatteschi, D.; Biagi, R.; Del Pennino, U.; De Renzi, V.; Gurevich, L.; Zant, H.S.J. van der

2004-01-01

Gold adsorbates of the dodecamanganese(III,IV) single-molecule magnet (SMM) [Mn 12 O 12 (L) 16 (H 2 O) 4 ] where L=16-(acetylthio)hexadecanoate have been prepared and investigated by X-ray photoelectron spectroscopy and scanning tunneling microscopy (STM). The successful imaging of Mn 12 molecules by STM represents a first step toward the magnetic addressing of individual SMMs and the development of molecule-based devices for magnetic information storage

Replacement of Oxygen by Sulfur in Small Organic Molecules. 3. Theoretical Studies on the Tautomeric Equilibria of the 2OH and 4OH-Substituted Oxazole and Thiazole and the 3OH and 4OH-Substituted Isoxazole and Isothiazole in the Isolated State and in Solution

Directory of Open Access Journals (Sweden)

Peter I. Nagy

2016-07-01

Full Text Available This follow-up paper completes the author’s investigations to explore the in-solution structural preferences and relative free energies of all OH-substituted oxazole, thiazole, isoxazole, and isothiazole systems. The polarizable continuum dielectric solvent method calculations in the integral-equation formalism (IEF-PCM were performed at the DFT/B97D/aug-cc-pv(q+(dz level for the stable neutral tautomers with geometries optimized in dichloromethane and aqueous solution. With the exception of the predictions for the predominant tautomers of the 3OH isoxazole and isothiazole, the results of the IEF-PCM calculations for identifying the most stable tautomer of the given species in the two selected solvents agreed with those from experimental investigations. The calculations predict that the hydroxy proton, with the exception for the 4OH isoxazole and 4OH isothiazole, moves preferentially to the ring nitrogen or to a ring carbon atom in parallel with the development of a C=O group. The remaining, low-fraction OH tautomers will not be observable in the equilibrium compositions. Relative solvation free energies obtained by the free energy perturbation method implemented in Monte Carlo simulations are in moderate accord with the IEF-PCM results, but consideration of the ΔGsolv/MC values in calculating ΔGstot maintains the tautomeric preferences. It was revealed from the Monte Carlo solution structure analyses that the S atom is not a hydrogen-bond acceptor in any OH-substituted thiazole or isothiazole, and the OH-substituted isoxazole and oxazole ring oxygens may act as a weak hydrogen-bond acceptor at most. The molecules form 1.0−3.4 solute−water hydrogen bonds in generally unexplored numbers at some specific solute sites. Nonetheless, hydrogen-bond formation is favorable with the NH, C=O and OH groups.

Disposition and biotransformation of the acetylenic retinoid tazarotene in humans.

Science.gov (United States)

Attar, Mayssa; Yu, Dale; Ni, Jinsong; Yu, Zhiling; Ling, Kah-Hiing John; Tang-Liu, Diane D-S

2005-10-01

Oral tazarotene, an acetylenic retinoid, is in clinical development for the treatment of psoriasis. The disposition and biotransformation of tazarotene were investigated in six healthy male volunteers, following a single oral administration of a 6 mg (100 microCi) dose of [14C]tazarotene, in a gelatin capsule. Blood levels of radioactivity peaked 2 h postdose and then rapidly declined. Total recovery of radioactivity was 89.2+/-8.0% of the administered dose, with 26.1+/-4.2% in urine and 63.0+/-7.0% in feces, within 7 days of dosing. Only tazarotenic acid, the principle active metabolite formed via esterase hydrolysis of tazarotene, was detected in blood. One major urinary oxidative metabolite, tazarotenic acid sulfoxide, accounted for 19.2+/-3.0% of the dose. The majority of radioactivity recovered in the feces was attributed to tazarotenic acid representing 46.9+/-9.9% of the dose and only 5.82+/-3.84% of dose was excreted as unchanged tazarotene. Thus following oral administration, tazarotene was rapidly absorbed and underwent extensive hydrolysis to tazarotenic acid, the major circulating species in the blood that was then excreted unchanged in feces. A smaller fraction of tazarotenic acid was further metabolized to an inactive sulfoxide that was excreted in the urine. Copyright (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association

Design, synthesis and anticonvulsant activity evaluation of 7-substituted-4H-[1,2,4]triazino[3,4-alpha]phthalazin-4-one derivatives

Energy Technology Data Exchange (ETDEWEB)

Sun, Xian-Yu; Quan, Zhe-Shan [Yanbian Univ., Yanji, Jilin (China). Key Lab. of Organism Functional Factors of the Changbai Mountain; Yanbian Univ., Yanji, Jilin (China). Coll. of Pharmacy; Guan, Li-Ping; Zhang, Lei; Wei, Cheng-Xi; Piao, Hu-Ri [Yanbian Univ., Yanji, Jilin (China). Key Lab. of Organism Functional Factors of the Changbai Mountain

2009-07-01

In this study, a novel series of 7-substituted-4H-[1,2,4]triazino[3,4-a]phthalazin-4-one derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that 7-hexyloxy-4H-[1,2,4]triazino[3,4-alpha]phthalazin-4-one 4e was the most potent with median effective dose (ED{sub 50}) value of 6.6 mg kg-1, median toxicity dose (TD{sub 50}) of 39.4 mg kg{sup -1}, providing a protective index (PI=TD{sub 50} /ED{sub 50}) value of 6.0. (author)

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

DEFF Research Database (Denmark)

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

2007-01-01

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

Accessing 2-substituted piperidine iminosugars by organometallic addition/intramolecular reductive amination: aldehyde vs. nitrone route.

Science.gov (United States)

Mirabella, S; Fibbi, G; Matassini, C; Faggi, C; Goti, A; Cardona, F

2017-11-07

A dual synthetic strategy to afford 2-substituted trihydroxypiperidines is disclosed. The procedure involved Grignard addition either to a carbohydrate-derived aldehyde or to a nitrone derived thereof, and took advantage of an efficient ring-closure reductive amination strategy in the final cyclization step. An opposite diastereofacial preference was demonstrated in the nucleophilic attack to the two electrophiles, which would finally produce the same piperidine diastereoisomer as the major product. However, use of a suitable Lewis acid in the Grignard addition to the nitrone allowed reversing the selectivity, giving access to 2-substituted piperidines with the opposite configuration at C-2.

t-Butyl group-substituted triphenylamine-containing orange-red fluorescent emitters for organic light-emitting diodes

Energy Technology Data Exchange (ETDEWEB)

Lee, Kum Hee; Kim, Chi Sik [Department of Chemistry, Sungkyunkwan University, Suwon, 440-746 (Korea, Republic of); Kim, Young Kwan, E-mail: kimyk@hongik.ac.kr [Department of Information Display, Hongik University, Seoul 121-791 (Korea, Republic of); Yoon, Seung Soo, E-mail: ssyoon@skku.edu [Department of Chemistry, Sungkyunkwan University, Suwon, 440-746 (Korea, Republic of)

2012-03-30

Efficient orange-red fluorescent compounds, 4-(dicyanomethylene)-2-adamantyl-6-(4-(N-(4-tert-butylphenyl) -N-(3,5-di-tert-butylphenyl)amino)benzene)vinyl-4H-pyran (DCATP) and 2,6-bis[4-(N-(4-tert-butylphenyl)-N-(3,5-di-tert-butylphenyl)amino)benzene] vinyl-4-(dicyanomethylene)-4H-pyran (BDCTP) containing the tert-butylated triphenylamine in donor moieties, were synthesized and characterized. In these red emitters, bulky groups, such as t-butyl group and adamantane were introduced to increase the steric hindrance between the red emitters. In particular, an efficient orange-red device containing the emitter DCATP as a dopant showed a luminous and power efficiency of 6.87 cd/A and 2.70 lm/W, respectively, at 20 mA/cm{sup 2} with the CIE coordinates of (0.48, 0.50) at 7.0 V. In addition, an efficient red organic light-emitting diode using BDCTP as a dopant exhibited a luminous and power efficiency of 2.30 cd/A and 1.31 lm/W, respectively, at 20 mA/cm{sup 2} and CIE coordinates of (0.61, 0.39). - Highlights: Black-Right-Pointing-Pointer Two orange-red emitters with t-butylated triphenylamine derivatives were studied. Black-Right-Pointing-Pointer We examine changes in electron D-A and electron D-A-D type in the terminal groups. Black-Right-Pointing-Pointer Electron D-A-D type material shows improved color chromaticity.

Enhancement of charge transport properties of small molecule semiconductors by controlling fluorine substitution and effects on photovoltaic properties of organic solar cells and perovskite solar cells.

Science.gov (United States)

Yun, Jae Hoon; Park, Sungmin; Heo, Jin Hyuck; Lee, Hyo-Sang; Yoon, Seongwon; Kang, Jinback; Im, Sang Hyuk; Kim, Hyunjung; Lee, Wonmok; Kim, BongSoo; Ko, Min Jae; Chung, Dae Sung; Son, Hae Jung

2016-11-01

We prepared a series of small molecules based on 7,7'-(4,4-bis(2-ethylhexyl)-4 H -silolo[3,2- b :4,5- b ']dithiophene-2,6-diyl)bis(4-(5'-hexyl-[2,2'-bithiophene]-5-yl)benzo[ c ][1,2,5]thiadiazole) with different fluorine substitution patterns ( 0F-4F ). Depending on symmetricity and numbers of fluorine atoms incorporated in the benzo[ c ][1,2,5]thiadiazole unit, they show very different optical and morphological properties in a film. 2F and 4F , which featured symmetric and even-numbered fluorine substitution patterns, display improved molecular packing structures and higher crystalline properties in a film compared with 1F and 3F and thus, 2F achieved the highest OTFT mobility, which is followed by 4F . In the bulk heterojunction solar cell fabricated with PC 71 BM, 2F achieves the highest photovoltaic performance with an 8.14% efficiency and 0F shows the lowest efficiency of 1.28%. Moreover, the planar-type perovskite solar cell (PSC) prepared with 2F as a dopant-free hole transport material shows a high power conversion efficiency of 14.5% due to its high charge transporting properties, which were significantly improved compared with the corresponding PSC device obtained from 0F (8.5%). From the studies, it is demonstrated that low variation in the local dipole moment and the narrow distribution of 2F conformers make intermolecular interactions favorable, which may effectively drive crystal formations in the solid state and thus, higher charge transport properties compared with 1F and 3F .

Simple, heart-smart substitutions

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Coronary artery disease - heart smart substitutions; Atherosclerosis - heart smart substitutions; Cholesterol - heart smart substitutions; Coronary heart disease - heart smart substitutions; Healthy diet - heart ...

Influence of mannosylation on immunostimulating activity of adamant-1-yl tripeptide.

Science.gov (United States)

Ribić, Rosana; Habjanec, Lidija; Frkanec, Ruža; Vranešić, Branka; Tomić, Srđanka

2012-07-01

The mannosylated derivative of adamant-1-yl tripeptide (D-(Ad-1-yl)Gly-L-Ala-D-isoGln) was prepared to study the effects of mannosylation on adjuvant (immunostimulating) activity. Mannosylated adamant-1-yl tripeptide (Man-OCH(2) CH(Me)CO-D-(Ad-1-yl)Gly-L-Ala-D-isoGln) is a non-pyrogenic, H(2) O-soluble, and non-toxic compound. Adjuvant activity of mannosylated adamantyl tripeptide was tested in the mouse model with ovalbumin as an antigen and in comparison to the parent tripeptide and peptidoglycan monomer (PGM, β-D-GlcNAc-(1→4)-D-MurNAc-L-Ala-D-isoGln-mesoDAP(εNH(2) )-D-Ala-D-Ala), a well-known effective adjuvant. The mannosylation of adamantyl tripeptide caused the amplification of its immunostimulating activity in such a way that it was comparable to that of PGM. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

Association of Dietary Proportions of Macronutrients with Visceral Adiposity Index: Non-Substitution and Iso-Energetic Substitution Models in a Prospective Study.

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Moslehi, Nazanin; Ehsani, Behnaz; Mirmiran, Parvin; Hojjat, Parvane; Azizi, Fereidoun

2015-10-26

We aimed to investigate associations between dietary macronutrient proportions and prospective visceral adiposity index changes (ΔVAI). The study included 1254 adults (18-74 years), from the Tehran Lipid and Glucose Study (TLGS), who were followed for three years. Dietary intakes were assessed twice using food frequency questionnaires. Associations of dietary macronutrient with ΔVAI and risk of visceral adiposity dysfunction (VAD) after three years were investigated. The percentage of energy intake from protein in the total population, and from fat in women, were associated with higher increases in VAI. A 5% higher energy intake from protein substituted for carbohydrate, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) was associated with higher ΔVAI. Higher energy intake from animal protein substituted for PUFAs was positively associated with ΔVAI. Substituting protein and PUFAs with MUFAs were related to higher ΔVAI. The associations were similar in men and women, but reached significance mostly among women. Risk of VAD was increased when 1% of energy from protein was replaced with MUFAs. Substituting protein for carbohydrate and fat, and fat for carbohydrate, resulted in increased risk of VAD in women. Higher dietary proportions of protein and animal-derived MUFA may be positively associated with ΔVAI and risk of VAD.

Synthesis of a Fluorescent Acridone Using a Grignard Addition, Oxidation, and Nucleophilic Aromatic Substitution Reaction Sequence

Science.gov (United States)

Goodrich, Samuel; Patel, Miloni; Woydziak, Zachary R.

2015-01-01

A three-pot synthesis oriented for an undergraduate organic chemistry laboratory was developed to construct a fluorescent acridone molecule. This laboratory experiment utilizes Grignard addition to an aldehyde, alcohol oxidation, and iterative nucleophilic aromatic substitution steps to produce the final product. Each of the intermediates and the…

Micro-, to nano-structural relationships in natural serpentines, derived from cationic substitutions.

Science.gov (United States)

Munoz, M.; Farges, F.; Andreani, M.; Ulrich, M.; Marcaillou, C.; Mathon, O.

2014-12-01

The understanding of the crystal chemistry of serpentine minerals (incl. antigorite, lizardite and chrysotile) is fundamental since serpentinization processes concern very large scientific domains: e.g., natural abiotic hydrogen production (Marcaillou et al., 2011), origins of life (Russell et al., 2010), fluid properties and mobility of metals in subduction zones (Kelley and Cottrell, 2009). This study aims at characterizing relations between the micro-, and nano-structures of the most abundant serpentine polytypes in the oceanic crust. Serpentine theoretical formula is Mg3Si2O5(OH)4 but several natural substitutions are possible and the formula may be written such as: (Mg,Fe2+,Fe3+,Al)3(Si,Al,Fe3+)2O5(OH)4; showing that Fe and Al may play an important role in the crystallization of serpentines. Preliminary crystal chemistry studies, suggest that, 1) the Al content alone cannot be directly correlated to serpentine polytypes (Andreani et al., 2008), 2) the amounts of tetrahedral iron can be significant in the presence of ferric iron (Marcaillou et al., 2011). Because magnetite is usually associated to serpentine, the Fe-speciation characterization of serpentine is delicate. Here, we provide the study of 33 magnetite-free serpentines containing various amounts of Fe and Al. The samples were characterized by SEM, Raman, XRF, as well as XANES, pre-edge, and EXAFS spectroscopy at the Fe K-edge. XANES experimental data were crosschecked and interpreted thanks to ab initio calculations and EXAFS shell-fitting. Also, preliminary 27Al-RMN data is presented. Results suggest relationships between the type and amount of substitution of trivalent cations in minerals, and the microstructures observed. Chrysotile incorporates less trivalent cations than other varieties, which tends to preserve the so-called misfit between the TO layers, and therefore the tubular structure of the mineral. Lizardites mainly involve Fe/Al Tschermak-type substitutions, while M-site vacancy charge

Adsorbed states of chlorophenol on Cu(110) and controlled switching of single-molecule junctions

Energy Technology Data Exchange (ETDEWEB)

Okuyama, H., E-mail: hokuyama@kuchem.kyoto-u.ac.jp; Kitaguchi, Y.; Hattori, T.; Ueda, Y.; Ferrer, N. G.; Hatta, S.; Aruga, T. [Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan)

2016-06-28

A molecular junction of substituted benzene (chlorophenol) is fabricated and controlled by using a scanning tunneling microscope (STM). Prior to the junction formation, the bonding geometry of the molecule on the surface is characterized by STM and electron energy loss spectroscopy (EELS). EELS shows that the OH group of chlorophenol is dissociated on Cu(110) and that the molecule is bonded nearly flat to the surface via an O atom, with the Cl group intact. We demonstrate controlled contact of an STM tip to the “available” Cl group and lift-up of the molecule while it is anchored to the surface via an O atom. The asymmetric bonding motifs of the molecule to the electrodes allow for reversible control of the junction.

preparation and nucleophilic substitution of the 2,4,6

African Journals Online (AJOL)

Mgina

Three methods for preparation of D-amino acids by nucleophilic substitution on derivatives of ... bioactivity of the peptide (Wenger 1985, ... Acetic acid (0.29 mL, 5 mmol) was added, and the mixture was further stirred for 5 h at rt under ... methanol/dichloromethane) to yield a white ... temperature, diluted with water, extracted.

[Glycosilated derivatives of substituted hydroxylamine. II. Phase transfer synthesis and investigation of glycosyl transfer reaction of glucosaminides of substituted hydroxylavine].

Science.gov (United States)

Kur'ianov, V O; Lushchik, A A; Chupakhina, T A

2013-01-01

1-(2-Acetamido-3,4,6,-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyloxy)-benzotriazole reacted in boiling dichloromethane, in the presence of Luis acids as a promotors with primary and secondary aliphatic and cycloaliphatic alcohols and diisopropilidene galactose with alkyl-O-1,2-trans-glucosaminides formation. It was shown that the other glucosaminides of substituted hydroxylamine are not participated in this reaction. Structures of glucosaminides were identify by 1H-NMR-spectroscopy and comparison with known compounds.

Design and synthesis of new of 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2, 5-dione derivatives as anticonvulsants.

Science.gov (United States)

Malik, Sachin; Ahuja, Priya; Sahu, Kapendra; Khan, Suroor Ahmad

2014-09-12

A series of 3-(benzo[d]isoxazol-3-yl)-N-substituted pyrrolidine-2, 5-dione (7a-7d, 8a-8d, 9a-9c) have been prepared and evaluated for their anticonvulsant activities. Preliminary anticonvulsant activity was performed using maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests after intraperitoneal (ip) injection into mice, which are the most widely employed models for early identification of anticonvulsant candidate. The acute neurological toxicity (NT) was determined applying rotorod test. The quantitative evaluation after oral administration in rats showed that the most active was 3-(benzo[d]isoxazol-3-yl)-1-(4-fluorophenyl) pyrrolidine-2, 5-dione (8a) with ED50 values of 14.90 mg/kg. Similarly the most potent in scPTZ was 3-(benzo[d]isoxazol-3-yl)-1-cyclohexylpyrrolidine-2, 5-dione (7d) with ED50 values of 42.30 mg/kg. These molecules were more potent and less neurotoxic than phenytoin and ethosuximide which were used as reference antiepileptic drugs. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Parasitic helminths: a pharmacopeia of anti-inflammatory molecules.

Science.gov (United States)

Johnston, M J G; MacDonald, J A; McKay, D M

2009-02-01

Infection with parasitic helminths takes a heavy toll on the health and well-being of humans and their domestic livestock, concomitantly resulting in major economic losses. Analyses have consistently revealed bioactive molecules in extracts of helminths or in their excretory/secretory products that modulate the immune response of the host. It is our view that parasitic helminths are an untapped source of immunomodulatory substances that, in pure form, could become new drugs (or models for drug design) to treat disease. Here, we illustrate the range of immunomodulatory molecules in selected parasitic trematodes, cestodes and nematodes, their impact on the immune cells in the host and how the host may recognize these molecules. There are many examples of the partial characterization of helminth-derived immunomodulatory molecules, but these have not yet translated into new drugs, reflecting the difficulty of isolating and fully characterizing proteins, glycoproteins and lipid-based molecules from small amounts of parasite material. However, this should not deter the investigator, since analytical techniques are now being used to accrue considerable structural information on parasite-derived molecules, even when only minute quantities of tissue are available. With the introduction of methodologies to purify and structurally-characterize molecules from small amounts of tissue and the application of high throughput immunological assays, one would predict that an assessment of parasitic helminths will yield a variety of novel drug candidates in the coming years.

Isotope-labelled folic acid derivatives

International Nuclear Information System (INIS)

Lewin, N.; Wong, E.T.

1976-01-01

The suggestion deals with the production of folic acid derivatives suitable as indicators or tracers for analyses of serum folates. These folic acid derivatives contain folic acid which is bound by one or both carboxyl groups to the amino nitrogen of compounds such as, e.g., tyramine, glycyl tyrosine, tyrosine, or the methyl ester of tyrosine. The derivative obtained can be substituted by a gamma emitter, e.g. the iodine isotope I 125. The radioactive derivative is used in the method for the competitive protein bonding to determine endogenic folates in the serum. (UWI) [de

Syntheses and biological activities of 13-substituted avermectin aglycons.

Science.gov (United States)

Mrozik, H; Linn, B O; Eskola, P; Lusi, A; Matzuk, A; Preiser, F A; Ostlind, D A; Schaeffer, J M; Fisher, M H

1989-02-01

The reactions of sulfonate esters of the allylic/homoallylic 13-alcohol of 5-O-(tert-butyldimethylsilyl)-22,23-dihydroavermectin B1a aglycon (1a) were investigated. Nucleophilic substitution gave 13 beta-chloro and 13 beta-iodo derivatives, while solvolytic reaction conditions yielded 13 alpha-methoxy, 13 alpha-fluoro, and 13 alpha-chloro products. A mixture of 13 alpha- and 13 beta-fluorides was obtained upon reaction with DAST. The 13 beta-iodide gave, upon elimination with lutidine, the 8(9),10(11),12(13),14(15)-tetraene. The 13 beta-alcohol and the rearranged 15-ol 13(14)-ene and 15-amino 13(14)-ene derivatives were obtained by substitution via the allylic carbonium ion. MEM ethers 11 and 12 of the two epimeric 13-ols were prepared by alkylation with MEM chloride. In contrast, methylation of 1a with MeI and Ag2O in CH2Cl2 occurred exclusively at the tertiary 7-hydroxy group and not at the secondary 13 alpha-ol. Oxidation of the allylic alcohol 1a proceeded under Swern conditions but not with MnO2 to the 13-oxo aglycon, which was reduced by NaBH4 exclusively to the natural 13 alpha-ol, while reductive amination with NaCNBH3-NH4OAc gave the 13 alpha-amine. The methoxime derivative was obtained in the form of the two geometric isomers. Anthelmintic activities against the sheep nematode Trichostrongylus colubriformis, miticidal activities against the two-spotted spider mite (Tetranychus urticae), and insecticidal activities against the southern armyworm (Spodoptera eridania) as well as the binding constants to a free living nematode (Caenorhabditis elegans) derived receptor assay were obtained and compared to avermectin B1a, 22,23-dihydroavermectin B1a, and the 13-deoxy-22,23-dihydroavermectin B1 aglycon related to the milbemycins. None of the newly prepared derivatives exceeded the potency of the three reference compounds. Lipophilic 13-substituents such as halogen, alkoxy, and methoxime retained high biological activities in all assays, while the more polar

Synthesis of Some O-Substituted Derivatives of Natural 6-hydroxymethyl-4-methoxy-2H-pyran-2-one (opuntiol)

International Nuclear Information System (INIS)

Shahzadi, T.; Akhtar, M.; Rehman, A.; Riaz, T.; Ashraf, M.

2013-01-01

This manuscript reports the synthesis of a series of new O-substituted derivatives of opuntiol (1) which is a naturally occurring compound isolated from a plant Opuntia dillenii Haw belonging to family Cactaceae. These derivatives 3a-t, were characterized by FAB-MS, IR, and 1H-NMR and then screened against acetylcholinesterase, butyrylcholinesterase, lipoxygenase and H-chymotrypsin enzymes. The screening results revealed that 6-(acetyloxy) methyl- 4-methoxy-2H-pyran-2-one (3b) and N-(2,5-dimethylphenyl)-2-((4-methoxy-6-oxo-2H-pyran-2-yl) methoxy)acetamide (3p) were found to be the inhibitor of butyrylcholinesterase while 6-(acetyloxy) methyl- 4-methoxy-2H-pyran-2-one (3b), 6-(ethoxymethyl)-4-methoxy-2H-pyran-2-one (3c), 4-methoxy-6-((phenylmethoxy)methyl)-2H-pyran-2-one (3g), 6-((2-bromoethyloxy)methyl)-4-methoxy-2H-pyran-2-one (3j), N-(5-chloro-2-ethoxyphenyl)-2-((4-methoxy-6-oxo-2H-pyran-2-yl)methoxy) acetamide (3r), N-(3,4-dimethylphenyl)-2-((4-methoxy-6-oxo-2H-pyran-2-yl)methoxy)acetamide (3s) N-(3,5-dimethylphenyl)-2-((4-methoxy-6-oxo-2H-pyran-2-yl)methoxy)acetamide (3t) were found to be active against H-chymotrypsin and among these 3s was the good inhibitor of this enzyme having IC50 value of 142.71 +- 0.22 micro moles/L. (author)

Roles of Retinoids and Retinoic Acid Receptors in the Regulation of Hematopoietic Stem Cell Self-Renewal and Differentiation

Directory of Open Access Journals (Sweden)

Louise E. Purton

2007-01-01

Full Text Available Multipotent hematopoietic stem cells (HSCs sustain blood cell production throughout an individual's lifespan through complex processes ultimately leading to fates of self-renewal, differentiation or cell death decisions. A fine balance between these decisions in vivo allows for the size of the HSC pool to be maintained. While many key factors involved in regulating HSC/progenitor cell differentiation and cell death are known, the critical regulators of HSC self-renewal are largely unknown. In recent years, however, a number of studies describing methods of increasing or decreasing the numbers of HSCs in a given population have emerged. Of major interest here are the emerging roles of retinoids in the regulation of HSCs.

Stereocomplementary Construction of Optically Active Bicyclo[4.3.0]nonenone Derivatives.

Science.gov (United States)

Mukai, Chisato; Kim, Jin Sung; Sonobe, Hiroshi; Hanaoka, Miyoji

1999-09-03

Treatment of (5S,6S)-5,6-bis(tert-butyldimethylsiloxy)-8-(substituted)oct-1-en-7-yne derivatives, prepared from diethyl L-tartrate, with Co(2)(CO)(8) afforded the corresponding cobalt-complexed enynes, which were subsequently exposed to the typical Pauson-Khand conditions to furnish highly stereoselectively or exclusively (2S,3S,6S)-2,3-bis(tert-butyldimethylsiloxy)-9-(substituted)bicyclo[4.3.0]non-1(9)-en-8-ones. On the other hand, (3S,4S)-1-(substituted)oct-7-en-1-yne-3,4-diol congeners produced, on exposure to the Pauson-Khand conditions, (2S,3S,6R)-2,3-dihydroxy-9-(substituted)bicyclo[4.3.0]-non-1(9)-en-8-one derivatives in a highly stereoselective manner. The newly developed procedure has been shown to be useful for construction of the 2,3-bis(oxygenated)-7-(substituted)bicyclo[4.3.0]non-6-en-8-one framework in a stereocomplementary as well as stereoselective fashion.

Computational Electrochemistry Study of Derivatives of Anthraquinone and Phenanthraquinone Analogues

DEFF Research Database (Denmark)

Wang, Zhen; Li, Anyang; Gou, Lei

2016-01-01

The substituent effect on fused heteroaromatic anthraquinone and phenanthraquinone are investigated by density functional calculations to determine some guidelines for designing potential cathode materials for rechargeable Li-ion batteries. The calculated redox potentials of the quinone derivatives...... change monotonically with increasing number of substitutions. Full substitution with electron-withdrawing groups brings the highest redox potential; however, mono-substitution results in the largest mass energy density. Carbonyl groups are the most favorable active Li-binding sites; moreover......, intramolecular lithium bonds can be formed between Li atoms and electronegative atoms from the substituent groups. The lithium bonds increase the redox potential by improving the thermodynamic stabilization of the lithiation derivatives. Furthermore, the calculation of nucleus-independent chemical shift...

Synthesis and evaluation of fluorine-substituted phenyl acetate derivatives as ultra-short recovery sedative/hypnotic agents.

Directory of Open Access Journals (Sweden)

Heng Zhang

Full Text Available BACKGROUND: Soft drugs are molecules that are purposefully designed to be rapidly metabolized (metabolically labile. In anesthesia, the soft drug is useful because it enables precise titration to effect and rapid recovery, which might allow swift and clear-headed recovery of consciousness and early home readiness. Propofol may cause delayed awakening after prolonged infusion. Propanidid and AZD3043 have a different metabolic pathway compared to propofol, resulting in a short-acting clinical profile. Fluorine imparts a variety of properties to certain medicines, including an enhanced absorption rate and improved drug transport across the blood-brain barrier. We hypothesized that the introduction of fluorine to the frame structure of propanidid and AZD3043 would further accelerate the swift and clear-headed recovery of consciousness. To test this hypothesis, we developed a series of fluorine-containing phenyl acetate derivatives. METHODOLOGY/PRINCIPAL FINDINGS: Fluorine-containing phenyl acetate derivatives were synthesized, and their hypnotic potencies and durations of LORR following bolus or infusion administration were determined in mice, rats and rabbits. The metabolic half-lives in the blood of various species were determined chromatographically. In vitro radioligand binding and γ-aminobutyric acidA (GABAA receptor electrophysiology studies were performed. Among the 12 synthesized fluorine-containing phenyl acetate derivatives, compound 5j induced comparable duration of LORR with AZD3043, but more rapid recovery than AZD3043, propanidid and propofol. The time of compound 5j to return to walk and behavioral recovery are approximately reduced by more than 50% compared to AZD3043 in mice and rats and rabbits. The HD50 of compound 5j decreased with increasing animal size. CONCLUSIONS/SIGNIFICANCE: The rapid recovery might make compound 5j suitable for precise titration and allow swift and clear-headed recovery of consciousness and early home

Evaluating the efficacy of a structure-derived amino acid substitution matrix in detecting protein homologs by BLAST and PSI-BLAST

Directory of Open Access Journals (Sweden)

Nalin CW Goonesekere

2009-06-01

Full Text Available Nalin CW GoonesekereDepartment of Chemistry and Biochemistry, University of Northern iowa, Cedar Falls, IA, USAAbstract: The large numbers of protein sequences generated by whole genome sequencing projects require rapid and accurate methods of annotation. The detection of homology through computational sequence analysis is a powerful tool in determining the complex evolutionary and functional relationships that exist between proteins. Homology search algorithms employ amino acid substitution matrices to detect similarity between proteins sequences. The substitution matrices in common use today are constructed using sequences aligned without reference to protein structure. Here we present amino acid substitution matrices constructed from the alignment of a large number of protein domain structures from the structural classification of proteins (SCOP database. We show that when incorporated into the homology search algorithms BLAST and PSI-blaST, the structure-based substitution matrices enhance the efficacy of detecting remote homologs. Keywords: computational biology, protein homology, amino acid substitution matrix, protein structure

Virtual substitution scan via single-step free energy perturbation.

Science.gov (United States)

Chiang, Ying-Chih; Wang, Yi

2016-02-05

With the rapid expansion of our computing power, molecular dynamics (MD) simulations ranging from hundreds of nanoseconds to microseconds or even milliseconds have become increasingly common. The majority of these long trajectories are obtained from plain (vanilla) MD simulations, where no enhanced sampling or free energy calculation method is employed. To promote the 'recycling' of these trajectories, we developed the Virtual Substitution Scan (VSS) toolkit as a plugin of the open-source visualization and analysis software VMD. Based on the single-step free energy perturbation (sFEP) method, VSS enables the user to post-process a vanilla MD trajectory for a fast free energy scan of substituting aryl hydrogens by small functional groups. Dihedrals of the functional groups are sampled explicitly in VSS, which improves the performance of the calculation and is found particularly important for certain groups. As a proof-of-concept demonstration, we employ VSS to compute the solvation free energy change upon substituting the hydrogen of a benzene molecule by 12 small functional groups frequently considered in lead optimization. Additionally, VSS is used to compute the relative binding free energy of four selected ligands of the T4 lysozyme. Overall, the computational cost of VSS is only a fraction of the corresponding multi-step FEP (mFEP) calculation, while its results agree reasonably well with those of mFEP, indicating that VSS offers a promising tool for rapid free energy scan of small functional group substitutions. This article is protected by copyright. All rights reserved. © 2016 Wiley Periodicals, Inc.

Mixed Quantum/Classical Theory for Molecule-Molecule Inelastic Scattering: Derivations of Equations and Application to N2 + H2 System.

Science.gov (United States)

Semenov, Alexander; Babikov, Dmitri

2015-12-17

The mixed quantum classical theory, MQCT, for inelastic scattering of two molecules is developed, in which the internal (rotational, vibrational) motion of both collision partners is treated with quantum mechanics, and the molecule-molecule scattering (translational motion) is described by classical trajectories. The resultant MQCT formalism includes a system of coupled differential equations for quantum probability amplitudes, and the classical equations of motion in the mean-field potential. Numerical tests of this theory are carried out for several most important rotational state-to-state transitions in the N2 + H2 system, in a broad range of collision energies. Besides scattering resonances (at low collision energies) excellent agreement with full-quantum results is obtained, including the excitation thresholds, the maxima of cross sections, and even some smaller features, such as slight oscillations of energy dependencies. Most importantly, at higher energies the results of MQCT are nearly identical to the full quantum results, which makes this approach a good alternative to the full-quantum calculations that become computationally expensive at higher collision energies and for heavier collision partners. Extensions of this theory to include vibrational transitions or general asymmetric-top rotor (polyatomic) molecules are relatively straightforward.

Generalized transition state theory. Quantum effects for collinear reactions of hydrogen molecules and isotopically substituted hydrogen molecules

International Nuclear Information System (INIS)

Garrett, B.C.; Truhlar, D.G.

1979-01-01

Canonical variational transition state theory, microcanonical variational transition state theory, and Miller's unified statistical theory were used in an attempt to correct two major deficiencies of the conventional transition state theory. These are: (1) the necessity of extra assumptions to include quantum mechanical tunneling effects and (2) the fundamental assumption that trajectories crossing a dividing surface in phase space proceed directly to products. The accuracy of these approximate methods were tested by performing calculations for several collinear reactions of hydrogen, deuterium, chlorine, or iodine, with five isotopes of hydrogen molecules and comparison of these results with those from accurate quantitative calculations of the reaction probabilities as functions of energy and of the thermal rate constants as functions of temperature. 49 references, 28 figures, 17 tables

Neutron scattering from a substitutional mass defect

International Nuclear Information System (INIS)

Williams, R.D.; Lovesey, S.W.

1985-06-01

The dynamic structure factor is calculated for a low concentration of light mass scatterers substituted in a cubic crystal matrix. A new numerical method for the exact calculation is demonstrated. A local density of states for the low momentum transfer limit, and the shifts and widths of the oscillator peaks in the high momentum transfer limit are derived. The limitations of an approximation which decouples the defect from the lattice is discussed. (author)

Dihydroxylation of 4-substituted 1,2-dioxines

DEFF Research Database (Denmark)

Robinson, Tony V; Pedersen, Daniel Sejer; Taylor, Dennis K

2009-01-01

The synthesis of 2-C-branched erythritol derivatives, including the plant sugar (+/-)-2-C-methylerythritol 2, was achieved through a dihydroxylation/reduction sequence on a series of 4-substituted 1,2-dioxines 3. The asymmetric dihydroxylation of 1,2-dioxines was examined, providing access...... to optically enriched dihydroxy 1,2-dioxanes 4. The synthesized 1,2-dioxanes were converted to other erythro sugar analogues and tetrahydrofurans through controlled cleavage of the endoperoxide linkage....

Biologically stable [18F]-labeled benzylfluoride derivatives

International Nuclear Information System (INIS)

Magata, Yasuhiro; Lang, Lixin; Kiesewetter, Dale O.; Jagoda, Elaine M.; Channing, Michael A.; Eckelman, William C.

2000-01-01

Use of the [ 18 F]-fluoromethyl phenyl group is an attractive alternative to direct fluorination of phenyl groups because the fluorination of the methyl group takes place under milder reaction conditions. However, we have found that 4-FMeBWAY showed femur uptake equal to that of fluoride up to 30 min in rat whereas 4-FMeQNB had a significantly lower percent injected dose per gram in femur up to 120 min. For these and other benzylfluoride derivatives, there was no clear in vivo structure-defluorination relationship. Because benzylchlorides (BzCls) are known alkylating agents, benzylfluorides may be alkylating agents as well, which may be the mechanism of defluorination. On this basis, the effects of substitution on chemical stability were evaluated by the 4-(4-nitro-benzyl)-pyridine (NBP) test, which is used to estimate alkylating activity with NBP. The effect of substitution on the alkylating activity was evaluated for nine BzCl derivatives: BzCl; 3- or 4-methoxy (electron donation) substituted BzCl; 2-, 3-, or 4-nitro (electron withdrawing) substituted BzCl; and 2-, 3-, or 4-chloro (electron withdrawing) substituted BzCl. Taken together, the alkylating reactivity of 3-chloro-BzCl was the weakest. This result was then applied to [ 18 F]-benzylfluoride derivatives and in vivo and in vitro stability were evaluated. Consequently, 3-chloro-[ 18 F]-benzylfluoride showed a 70-80% decrease of defluorination in both experiments in comparison with [ 18 F]-benzylfluoride, as expected. Moreover, a good linear relationship between in vivo femur uptake and in vitro hepatocyte metabolism was observed with seven 18 F-labeled radiopharmaceuticals, which were benzylfluorides, alkylfluorides, and arylfluorides. Apparently, the [ 18 F]-fluoride ion is released by metabolism in the liver in vivo. In conclusion, 3-chloro substituted BzCls are the most stable, which suggests that 3-chloro benzylfluorides will be the most chemically stable compound. This result should be important in

Electrical characterization of single molecule and Langmuir–Blodgett monomolecular films of a pyridine-terminated oligo(phenylene-ethynylene derivative

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Henrry M. Osorio

2015-05-01

Full Text Available Monolayer Langmuir–Blodgett (LB films of 1,4-bis(pyridin-4-ylethynylbenzene (1 together with the “STM touch-to-contact” method have been used to study the nature of metal–monolayer–metal junctions in which the pyridyl group provides the contact at both molecule–surface interfaces. Surface pressure vs area per molecule isotherms and Brewster angle microscopy images indicate that 1 forms true monolayers at the air–water interface. LB films of 1 were fabricated by deposition of the Langmuir films onto solid supports resulting in monolayers with surface coverage of 0.98 × 10−9 mol·cm−2. The morphology of the LB films that incorporate compound 1 was studied using atomic force microscopy (AFM. AFM images indicate the formation of homogeneous, monomolecular films at a surface pressure of transference of 16 mN·m−1. The UV–vis spectra of the Langmuir and LB films reveal that 1 forms two dimensional J-aggregates. Scanning tunneling microscopy (STM, in particular the “STM touch-to-contact” method, was used to determine the electrical properties of LB films of 1. From these STM studies symmetrical I–V curves were obtained. A junction conductance of 5.17 × 10−5 G0 results from the analysis of the pseudolinear (ohmic region of the I–V curves. This value is higher than that of the conductance values of LB films of phenylene-ethynylene derivatives contacted by amines, thiols, carboxylate, trimethylsilylethynyl or acetylide groups. In addition, the single molecule I–V curve of 1 determined using the I(s method is in good agreement with the I–V curve obtained for the LB film, and both curves fit well with the Simmons model. Together, these results not only indicate that the mechanism of transport through these metal–molecule–metal junctions is non-resonant tunneling, but that lateral interactions between molecules within the LB film do not strongly influence the molecule conductance. The results presented here

INFLUENCE OF SOLUBLE PLACENTAL TISSUE-DERIVED MOLECULES UPON EXPRESSION OF ADHESION MOLECULES BY EA.HY926 ENDOTHELIAL CELLS

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O. I. Stepanova

2011-01-01

Full Text Available Abstract.  Leukocyte  recruitment  to  placental  tissue  is  an  important  factor  of  its  development.  In  this respect, adhesion molecules at the endothelial cell surface represent a key determining factor of leukocyte adhesion and their trans-endothelial migration. The goal of investigation was to evaluate changed expression of adhesion molecules on the endothelial cells induced by supernates of placental tissue cultures. Placental tissue supernatants produced by the first- and third-trimester placental tissue from normal pregnancy, as well as from women with gestosis, induced higher expression of CD31, CD9, CD62E, CD62P, CD34, CD54, CD51/61, CD49d  and  integrin  β7  expression  by  endothelial  cells,  as  compared  with  their  baseline  levels.  However, the  supernates  from  pre-eclamptic  placental  tissue (3rd  trimester  caused  an  increased  CD9  expression by  endothelial  cells,  as  compared  with  effects  of placental  supernates  from  eclampsia-free  cases.  Our data  contribute  to  understanding  a  possible  role  of endothelial cell adhesion molecules in recruitment of leukocytes to placental tissue and possible participation of adhesion molecules in pathogenesis of pre-eclampsia. The work was supported by a grant from Russian Ministry of Education and Science ГК №02.740.11.0711 and Presidential grant № НШ-3594.2010.7 and МД-150.2011.7. (Med. Immunol., 2011, vol. 13, N 6, pp 589-596

Profiles of equilibrium constants for self-association of aromatic molecules.

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Beshnova, Daria A; Lantushenko, Anastasia O; Davies, David B; Evstigneev, Maxim P

2009-04-28

Analysis of the noncovalent, noncooperative self-association of identical aromatic molecules assumes that the equilibrium self-association constants are either independent of the number of molecules (the EK-model) or change progressively with increasing aggregation (the AK-model). The dependence of the self-association constant on the number of molecules in the aggregate (i.e., the profile of the equilibrium constant) was empirically derived in the AK-model but, in order to provide some physical understanding of the profile, it is proposed that the sources for attenuation of the equilibrium constant are the loss of translational and rotational degrees of freedom, the ordering of molecules in the aggregates and the electrostatic contribution (for charged units). Expressions are derived for the profiles of the equilibrium constants for both neutral and charged molecules. Although the EK-model has been widely used in the analysis of experimental data, it is shown in this work that the derived equilibrium constant, K(EK), depends on the concentration range used and hence, on the experimental method employed. The relationship has also been demonstrated between the equilibrium constant K(EK) and the real dimerization constant, K(D), which shows that the value of K(EK) is always lower than K(D).

Photo-rearrangements of some 3-allyloxy-2-phenyl-chromones: Synthesis of vinyl substituted benzopyronopyranes

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Rupesh Kumar

2008-10-01

Full Text Available Photochemical reactions of some 3-allyloxy-2-phenylchromones have been studied. Photoreactions of the compounds afforded substituted pyronopyrane derivatives through the 1,4-biradicals.

Anti-leishmanial and structure-activity relationship of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives

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Asunción Burguete

2008-12-01

Full Text Available A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E-3-(3,4,5-trimethoxy-phenyl-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.

A linear solvation energy relationship study for the reactivity of 2-substituted cyclohex-1-enecarboxylic and 2-substituted benzoic acids with diazodiphenylmethane in aprotic and protic solvents

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JASMINA B. NIKOLIC

2007-12-01

Full Text Available The rate constants for the reaction of 2-substituted cyclohex-1-enylcarboxylic acids and the corresponding 2-substituted benzoic acids with diazodiphenyl methane were determined in various aprotic solvents at 30 ºC. In order to explain the kinetic results through solvent effects, the second order rate constants of the reaction of the examined acids were correlated using the Kamlet–Taft solvatechromic equation. The correlations of the kinetic data were carried out by means of multiple linear regression analysis and the solvent effects on the reaction rates were analyzed in terms of the contributions of the initial and transition state. The signs of the equation coefficients support the proposed reaction mechanism. The quantitative relationship between the molecular structure and the chemical reactivity is discussed, as well as the effect of geometry on the reactivity of the examined molecules.

Evaluating the efficacy of a structure-derived amino acid substitution matrix in detecting protein homologs by BLAST and PSI-BLAST.

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Goonesekere, Nalin Cw

2009-01-01

The large numbers of protein sequences generated by whole genome sequencing projects require rapid and accurate methods of annotation. The detection of homology through computational sequence analysis is a powerful tool in determining the complex evolutionary and functional relationships that exist between proteins. Homology search algorithms employ amino acid substitution matrices to detect similarity between proteins sequences. The substitution matrices in common use today are constructed using sequences aligned without reference to protein structure. Here we present amino acid substitution matrices constructed from the alignment of a large number of protein domain structures from the structural classification of proteins (SCOP) database. We show that when incorporated into the homology search algorithms BLAST and PSI-blast, the structure-based substitution matrices enhance the efficacy of detecting remote homologs.

Modeling charge transport properties of cyano-substituted PPV

International Nuclear Information System (INIS)

Correia, Helena M.G.; Ramos, Marta M.D.

2003-01-01

In recent years, poly (p-phenylenevinylene) (PPV) and its derivatives have attracted much interest due to their applications in light-emitting diodes (LEDs). One of the issues that determine device performance is the transport of charge carriers along the polymer strands. For that reason, we investigate the influence of cyano substitution on geometry and electronic behaviour of PPV chains using self-consistent quantum molecular dynamics simulations. Our results suggest that substitution by cyano groups induce distortion in the PPV chains and a charge rearrangement among the polymer atoms. Specifically addressed is the issue concerning estimates of charge (electron and hole) mobility by computer experiments. Significant differences have been found both in the strength of the electric field needed to move positive and negative charge carriers along the polymer chain as well as in charge mobility