2D-QSAR Study of Indolylpyrimidines Derivative as Antibacterial against Pseudomonas aeruginosa and Staphylococcus aureus: A Comparative Approach

A set of 15 indolylpyrimidine derivatives with their antibacterial activities in terms of minimum inhibitory concentration against the gram-negative bacteria Pseudomonas aeruginosa and gram-positive Staphylococcus aureus were selected for 2D quantitative structure activity relationship (QSAR) analysis. QSAR was performed using a combination of various descriptors such as steric, electronic and topological. Stepwise regression method was used to derive the most significant QSAR equation for predicting the inhibitory activity of this class of molecules. The best QSAR model was further validated by a leave one out technique as well as by the random trials. A high correlation between experimental and predicted inhibitory values was observed. A comparative picture of behavior of indolylpyrimidines against both of the microorganisms is discussed

Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review

Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharmacology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application). Various methods such as GC, LCâMS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and quantitative analysis of carbamazepine in biological samples throughout all phases of clinical research and quality control. The article incorporates various reported methods developed to help analysts in choosing crucial parameters for new method development of carbamazepine and its derivatives and also enumerates metabolites, and impurities reported so far. Keywords: Carbamazepine, HPLC, LCâMS/MS, HPTLC, RP-UFLC, Micellar electrokinetic chromatograph

Design and synthesis of novel thiazolidine-2,4-diones as hypoglycemic agents

Thiazolidinediones are well known for causing reduction in blood glucose levels. A number of thiazolidinediones have been approved for clinical use in diabetes. Present research work is based on the synthesis of thiazolidinedione derivatives that were designed previously using 2D QSAR for antidiabetic activity. Thiazolidine-2,4-diones derivatives having carboxylic ester appendages at N-3 and 5-substituted benzylidene were studied and the syntheses of only four derivatives were performed that were predicted to have promising antidiabetic activities. Their effect on hypoglycemic activity was performed using a sucrose loaded model. Compounds 5a and 5b were found to have prominent activities at 100 mg/kg by oral route administration

Design and synthesis of novel 4-substituted 1,4-dihydropyridine derivatives as hypotensive agents

Calcium-channel blockers have an important role in the treatment of several cardiovascular disorders. Derivatives of 1,4-dihydropyridines are one of the most potent calcium antagonists. In this study a series of novel 1,4-dihydropyridine calcium channel blockers of general formula diethyl 4-(4-substituted phenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate were synthesized and tested for hypotensive activity, including electrocardiographic and effect on heart rate. Compound diethyl 4-(4-benzyloxy phenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate (DHP I) and diethyl 4-(2-(2-chlorobenzyloxy) phenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate (DHP III), were the most potent in this series. All synthesized compounds lowered rat blood pressure significantly in comparison with DMSO as control and nifedipine was used as positive control

Synthesis of new 4-aryl/alkyl-1-(5',5'-diphenyl-4'-oxo-1<i>'</i>-H-4<i>'</i>,5<i>'</i>-dihydroimidazolidin- 2<i>'</i>-yl)-3-hydroxy-1,2,4-triazolidine-5-thione derivatives as potential anti-cancer agents

690-694New 4-aryl/alkyl-1-(5',5'-diphenyl-4'-oxo-1'-H-4',5'-dihydroimidazolidin- 2'-yl)-3-hydroxy-1,2,4-triazolidine-5-thiones 3 have been prepared by the reaction of 2-carbethoxy-(5',5'-diphenyl-4'oxo-1' -H-4',5'-dihydroimidazolidin-2'-yl)-hydrazine 2 with various aryl/alkylisothiocyanates. Their anti-bacterial, anti-fungal, anthelmintic and anti-cancer activities are reported

Synthesis of new 4-aryl/alkyl-1-(5',5'-diphenyl-4'-oxo-1<i>'</i>-H-4<i>'</i>,5<i>'</i>-dihydroimidazolidin- 2<i>'</i>-yl)-3-hydroxy-1,2,4-triazolidine-5-thione derivatives as potential anti-cancer agents

690-694New 4-aryl/alkyl-1-(5',5'-diphenyl-4'-oxo-1'-H-4',5'-dihydroimidazolidin- 2'-yl)-3-hydroxy-1,2,4-triazolidine-5-thiones 3 have been prepared by the reaction of 2-carbethoxy-(5',5'-diphenyl-4'oxo-1' -H-4',5'-dihydroimidazolidin-2'-yl)-hydrazine 2 with various aryl/alkylisothiocyanates. Their anti-bacterial, anti-fungal, anthelmintic and anti-cancer activities are reported

Comparative residue interaction analysis (CoRIA): a 3D-QSAR approach to explore the binding contributions of active site residues with ligands

A novel approach termed comparative residue-interaction analysis (CoRIA), emphasizing the trends and principles of QSAR in a ligand–receptor environment has been developed to analyze and predict the binding affinity of enzyme inhibitors. To test this new approach, a training set of 36 COX-2 inhibitors belonging to nine families was selected. The putative binding (bioactive) conformations of inhibitors in the COX-2 active site were searched using the program DOCK. The docked configurations were further refined by a combination of Monte Carlo and simulated annealing methods with the Affinity program. The non-bonded interaction energies of the inhibitors with the individual amino acid residues in the active site were then computed. These interaction energies, plus specific terms describing the thermodynamics of ligand–enzyme binding, were correlated to the biological activity with G/PLS. The various QSAR models obtained were validated internally by cross validation and boot strapping, and externally using a test set of 13 molecules. The QSAR models developed on the CoRIA formalism were robust with good r 2, q 2 and r pred2 values. The major highlights of the method are: adaptation of the QSAR formalism in a receptor setting to answer both the type (qualitative) and the extent (quantitative) of ligand–receptor binding, and use of descriptors that account for the complete thermodynamics of the ligand–receptor binding. The CoRIA approach can be used to identify crucial interactions of inhibitors with the enzyme at the residue level, which can be gainfully exploited in optimizing the inhibitory activity of ligands. Furthermore, it can be used with advantage to guide point mutation studies. As regards the COX-2 dataset, the CoRIA approach shows that improving Coulombic interaction with Pro528 and reducing van der Waals interaction with Tyr385 will improve the binding affinity of inhibitors