T.K. Maity
Accepted Abstracts: J Diabetes Metab
I n view of the biological importance, some substituted Phthalimide derivatives having different activities like Anti-HIV and hypoglycemic agents, were engaged in further structural development studies of α-glucosidase inhibitors. A set of 17 compounds of Phthalimide was subjected to three dimensional quantitative structure activity relationship analysis using k nearest neighbour molecular field analysis method to design 4,5,6,7-substituted phthalimide derivative as novel α-glucosidase inhibitors. The 3D-QSAR model was developed using 11 compounds (training set) and its predictive ability was assessed using a test set of 6 compounds. The highly predictive 3D-QSAR models by KNN method for molecular field analysis (MFA) have cross-validated coefficient q2 value was 0.9451, Predicted r2 value was 0.9610. The results have showed that phthalimide group are necessary for activity and halogen group in phthalimide nucleus enhanced the biological activity. Homology modeling showed Enzyme, α-glucosidase had highest amino acid sequence identity with the amino acid sequence of sulfolobus sulfataricus α-glucosidase Mal-A PDB ID 2G3M (F-chain). GRIP batch Docking indicated ligands were bind in the ATP pocket in cavity number four by requiring minimum energy score (between -40 to -60) and Pi-stacking, Hydrophobic interaction, VDW interaction with TRP618 was found to be crucial for selectivity among other α-glucosidase. The results of 3D-QSAR & docking studies validated each other. The combination of both methodologies provided a powerful tool directed to the design of novel and selective 2G3MF receptor inhibitors. All the Molecular Modeling studies were completed by the using of software V-LIFE MDS 3.0.
