A Structure-Based 3D-QSAR and Docking Studies on a Series of Indolealkanoic Acid Derivatives as Diabetes Mellitus Inhibitors

Comparative molecular field analysis and comparative molecular similarity indices analysis (CoMSIA) based on three dimensional quantitative structure-activity relationship (3D-QSAR) studies were conducted on a series (28 compounds) of indolealkanoic acid derivatives as potent diabetes mellitus inhibitors. The best prediction was obtained with a CoMFA standard model (q= 0.850, r= 0.983) and with CoMSIA combined steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields (q= 0.856, r= 0.977). CoMFA and CoMSIA contour maps were then used to analyze the structural features of ligands to account for the activity in terms of positively contributing physiochemical properties such as steric, electrostatic, hydrophobic and hydrogen bond donor fields. The resulting contour maps produced by the best CoMFA and CoMSIA models were used to identify the structural features relevant to the biological activity in this series of analogs. The information obtained from CoMFA and CoMSIA 3-D contour maps can be used for the design of indolealkanoic acid derivatives as potent inhibitors of diabetes mellitus. The binding mode of the high active compound at the active site of Novel Benzothiazepine Inhibitor in Complex with human Aldose Reductase (PDB id: 3P2V) was explored using FlexX docking program and hydrogen-bonding interactions were observed between the inhibitor and the target.