2D and 3D QSAR studies and antibacterial activity of 4-methyl-3-(6-{[arylmethylene] amino}pyridin-3-YL)-2H-chromen-2-one derivatives

4-methyl-3-(6-{[arylmethylene] amino} pyridin-3-yl)-2H-chromen-2-one derivatives containing different functional groups have been synthesized and screened for their antibacterial activity against four different strains of bacteria. 2D and 3D QSAR analysis of synthesized derivatives were performed on Vlife MDS 3.5 software. The data set for QSAR studies encompassed activities of 64 molecules divided into training and test set. The best models were selected on basis of correlation coefficient (r2) and internal and external predictivity (Pred_r2) of the QSAR model. QSAR models reveled that electronic, steric and liphophillic parameters have correlation with antibacterial activity. The 3D interactions and their contributions indicate multi-targeted mode of action of the compounds.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Synthesis, Characterization and Quantification of Simvastatin Metabolites and Impurities

Simvastatin is used in treatment of hypercholesterolemia because it regulates cholesterol synthesis as a result of its β-hydroxy acid acting as an inhibitor of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA). The present communication deals with synthesis, characterization and development of accurate, precise and sensitive Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method for simultaneous estimation of simvastatin and its synthetic impurities. The impurities methyl ether and β-hydroxy acid of simvastatin were synthesized in the laboratory and characterized by MS, NMR and FT-IR spectroscopy. The separation of simvastatin and its impurities was carried out on an isocratic JASCO RP-HPLC system using KYA TECH HIQ SIL C18 column (150 × 4.6 mm internal diameter, particle size 5 μm) operating at ambient temperature using acetonitrile:water (80:20 v/v) with 0.1% orthophosphoric acid as mobile phase. The method developed for HPLC analysis of three impurities along with simvastatin was validated using ICH Q2B (R1) guidelines and it complied with these guidelines. The results of analysis were found to be in the range of 98.14% to 101.89% for all analytes with acceptable accuracy and precision. The method can be used for detection and quantification of synthetic impurities in bulk or formulations of simvastatin

Two- and three-dimensional quantitative structure-activity relationships studies on a series of diuretics

Diuretics are an attractive class of drugs for the treatment of various disorders and in combination with some cardiovascular drugs. In the present work, 2D and 3D quantitative structure-activity relationship studies have been conducted on a series of diuretics. Significant correlation coefficients (r2 = 0.81 and q2 = 0.65, r2 = 0.91 and q2 = 0.85) were obtained, indicating potential of the models generated for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values obtained from the 2D and 3D models were in good agreement with the experimental results. The final QSAR models, along with the information obtained from 3D steric and electrostatic contour maps and 2D contributions should be useful for the design of diuretics having improved potency.Colegio de Farmacéuticos de la Provincia de Buenos Aire

3D QSAR ANALYSIS OF 2,4-DISUBSTITUTED 1,5-BENZODIAZEPINE DERIVATIVES AS CNS DEPRESSANTS

New 2,4-disubstituted-1,5-benzodiazepine derivatives containing different functional groups have been screened for their CNS depressant activity. The synthesized benzodiazepine derivatives were screened for CNS depressant activity using the actophotometer model for mice. QSAR studies of synthesized derivatives were performed on Vlife MDS 3.5 software. The data set for QSAR studies encompassed activities of 45 molecules and 252 descriptors calculated by Vlife MDS 3.5. The training set comprised of 36 molecules and test set of 9 molecules. QSAR equation revealed that some electronic, steric and liphophillic parameters have correlation with CNS depressant activity. The best equation was selected on basis of correlation coefficient (r 2 ) and predicitivity of equation