Molecular electrostatic potentials as input for the alignment of HIV-1 integrase inhibitors in 3D QSAR

Comparative molecular similarity indices analysis (CoMSIA), a three-dimensional quantitative structure activity relationship (3D QSAR) paradigm, was used to examine the correlations between the calculated physicochemical properties and the in vitro activities (3'-processing and 3'-strand transfer inhibition) of a series of human immunodeficiency virus type 1 (HIV-1) integrase inhibitors. The training set consisted of 34 molecules from five structurally diverse classes: salicylpyrazolinones, dioxepinones, coumarins, quinones, and benzoic hydrazides. The data set was aligned using extrema of molecular electrostatic potentials (MEPs). The predictive ability of the resultant model was evaluated using a test set comprised of 7 molecules belonging to a different structural class of thiazepinediones. A CoMSIA model using an MEP-based alignment showed considerable internal as well external predictive ability (r2(cv) = 0.821, r2(pred) = 0.608 for 3'-processing; and r2(cv) = 0.759, r2(pred.) = 0.660 for 3'-strand transfer).     

Newtonian viscosity behavior of dilute to moderately concentrated solutions of cellulose acetate butyrate

The Newtonian viscosity behavior of dilute to moderately concentrated solutions of cellulose acetate butyrate in dioxane was investigated at different temperatures. The viscosity data were analyzed in terms of Martin's and Fedor's relationships and also generalized in terms of reduced variables. The rheological behavior of cellulose acetate butyrate solutions in the whole range of concentrations is determined by the parameter (K_MC [n]). The temperature dependence of viscosities was expressed by the Arrhenius-Frenkel-Eyring equation and the activation energy of viscous flow of polymer solutions (ΔGv) was calculated. ΔGv increases with concentration of polymer solution and is independent of temperature. The preexponential factor, A, related to activation entropy, decreases with concentration of polymer solution. The thermodynamic parameter of viscous flow for cellulose acetate butyrate (CAB)-dioxane solutions is indicative of moderately stiff structure for CAB in solutions.     

Antioxidant and Hepatoprotective Activity of a Lichen Usnea ghattensis in Vitro

Antioxidative and hepatoprotective activity of a cultured lichen Usnea ghattensis has been studied. The methanolic extract of cultured lichen U. ghattensis showed good antioxidant activity by preventing lipid peroxidation by 67% and 86% in Trolox-equivalent antioxidant capacity at 20 microg/ml. It also showed superoxide, 1,1-diphenyl-2-picrylhydrazyl, nitric oxide, and hydroxyl radical-scavenging activity, 89%, 89.6%, 94.8%, and 89.6%, respectively, and found levels higher then that known for the synthetic antioxidants butylated hydroxytoluene, butylated hydroxyanisol, and quercetin at 20 microg/ml concentration. The cultured lichen extract also showed hepatoprotection against ethanol-induced toxicity in the mice liver slice culture model by a significant decrease in the antioxidant enzymes, glutathione peroxidase, catalase, and superoxide dismutase, along with a decrease in lipid peroxidation and lactate dehydrogenase release.     

Role of Vitamins B-3 and C in the Fashioning of Granules in UASB Reactor Sludge

Whereas a myriad of possible factors have been reported which effect the formation of granules in a upflow anaerobic sludge blanket (UASB) reactor and influence their properties, there is no study on the effect of vitamins on the granulation of UASB reactor sludge. The present study was undertaken to bridge this gap. It was seen that vitamins helped in better granule formation??as reflected by favorable size distribution, sludge volume index, and settling velocity??compared to controls. The vitamin-spiked reactors also achieved >85?% COD removal efficiency in half the number of days the unspiked reactors took. The vitamin supplements were effective at concentrations????1?mg/l. Hence, their use in expediting granule formation as also in developing better-quality granules appears economically viable.     

Thermal oxidation of blends of poly(ethylene oxide) and poly(methyl methacrylate)

Thermal oxidation of poly(ethylene oxide) (PEO) and its blends with poly(methyl methacrylate) (PMMA) were studied using oxygen uptake measurements. The rates of oxidation and maximum oxygen uptake contents were reduced as the content of PMMA was increased in the blends. The results were indicative of a stabilizing effect by PMMA on the oxidation of PEO. The oxidation reaction at 140°C was stopped at various stages and PMMA was separated from PEO and its molecular weights were measured by gel permeation chromatography (GPC). The decrease in the number-average molecular weight of PMMA was larger as the content of PEO increased in the blends. The visual appearance of the films suggested that phase separation did not occur after thermal oxidation. The activation energy for the rates of oxidation in the blends was slightly increased compared to pure PEO. © 1992 John Wiley & Sons, Inc.     

Fabrication and characterization of ZnTe/CdSe thin film solar cells

Thin film solar cells have been prepared and investigated by using indium-doped n-CdSe in conjunction with p-ZnTe. The films are prepared on indium tin oxide (ITO) coated glass substrates by the thermal evaporation. Thin film layers have been deposited without breaking vacuum by utilizing a mask rotating system. Silver has been used as a stimulator for bringing improvement in the crystallinity and electrical behaviour of ZnTe thin films. Indium is used for obtaining the back ohmic contacts. The solar cells thus produced have been characterized by I–V-, C–V-, and spectral response measurements. The maximum open circuit voltage, the short circuit current density, and the efficiency are obtained as 415 mV, 11.60 mA cm⁻² and 1.86%, respectively under 100 mW cm⁻² input optical power. The diffusion potential and depletion width are found to be 1.42 eV and 21 nm, respectively.     

Eigen value analysis of HIV-1 integrase inhibitors.

A three-dimensional quantitative structure activity relationship using the eigen value analysis (EVA) paradigm applied to 41 HIV-1 integrase inhibitors that inhibit integrase mediated cleavage (3'-processing step) and integration (3'-strand transfer step) in vitro was performed. The training set consisted of 35 molecules from five structurally diverse classes: salicylhydrazines, lichen acids, coumarins, quinones, and thiazolothiazepines. Models derived using semiempirical (MOPAC AM1 and PM3) calculated normal-mode frequencies were compared. The predictive ability of each resultant model was evaluated using a test set comprised of six molecules belonging to a different structural class: hydrazides. Models derived using AM1 method showed considerable internal as well as external predictivity (r(2)(cv) = 0.806, r(2)(pred) = 0.761 for 3'-processing and r(2)(cv) = 0.677, r(2)(pred) = 0.591 for 3'-strand transfer).     

Virtual and experimental high-throughput screening (HTS) in search of novel inosine 5′-monophosphate dehydrogenase II (IMPDH II) inhibitors

IMPDH (Inosine 5??-monophosphate dehydrogenase) catalyzes a rate-limiting step in the de novo biosynthesis of guanine nucleotides. IMPDH inhibition in sensitive cell types (e.g., lymphocytes) blocks proliferation (by blocking RNA and DNA synthesis as a result of decreased cellular levels of guanine nucleotides). This makes it an interesting target for cancer and autoimmune disorders. Currently available IMPDH inhibitors such as mycophenolic acid (MPA, uncompetitive inhibitor) and nucleoside analogs (e.g., ribavirin, competitive inhibitor after intracellular activation by phosphorylation) have unfavorable tolerability profiles which limit their use. Hence, the quest for novel IMPDH inhibitors continues. In the present study, a ligand-based virtual screening using IMPDH inhibitor pharmacophore models was performed on in-house compound collection. A total of 50,000 virtual hits were selected for primary screen using in vitro IMPDH II inhibition up to 10???M. The list of 2,500 hits (with >70?% inhibition) was further subjected to hit confirmation for the determination of IC₅₀ values. The hits obtained were further clustered using maximum common substructure based formalism resulting in 90 classes and 7 singletons. A thorough inspection of these yielded 7 interesting classes in terms of mini-SAR with IC₅₀ values ranging from 0.163???M to little over 25???M. The average ligand efficiency was found to be 0.3 for the best class. The classes thus discovered represent structurally novel chemotypes which can be taken up for further development.     

Antihyperglycemic,antihyperlipidemic and antioxidative evaluation of compounds from Senna sophera (L.) Roxb in streptozotocin-induced diabetic rats

Senna sophera (L.) Roxb (Common name: Kasunda, Baner) (Leguminosae) is used as traditional medicine in Africa and Asia. The compounds were isolated from methanolic extract of leaves of Senna sophera (MFCS). Compound A was identified as Hexahydroxy diphenic acid and Compound B as Kaempferol. MFCS administration to diabetic rats exhibited significant reduction in the blood sugar level and showed gain in body weight. After the treatment of 100 mg/kg of MFCS, the blood sugar level was reduced to 52.33 ± 2.83 mg/dl in comparison to the blood sugar level of vehicle control 76.66 ± 3.17 mg/dl, whereas treatment with 50 mg/kg of MFCS reduced the blood sugar level slightly (72.33 ± 2.42 mg/dl). The daily continuous administration of MFCS for a period of 21 days normalised the serum lipid levels confirming the effect of MFCS on diabetic hyperlipidemia. Treatment with MFCS also reversed the activities of antioxidants, which could be a result of decreased lipid peroxidation.