Computational studies of some biscoumarin and biscoumarin thiourea derivatives as alfa-glucosidase inhibitors

Abstract

Quantitative structure-activity relationship and molecular docking studies of 35 compounds of Biscoumarins and Biscoumarins thiourea derivatives as alfa-glucosidase inhibitors was performed. Density Functional Theory (DFT) method was employed for complete geometry optimization of the alfa-glucosidase inhibitors. Genetic Function Algorithm (GFA) of the material studio was utilized to develop four models. Model 1 was found to be the best model with R2 = 0.914362, R2 adj = 0.892953, Q2cv = 0.858197 and R2 pred = 0.614745. The proposed model is robustness and predicted with good internal and external validation. The descriptors should be considered when improving the inhibitory activities of biscoumarin derivatives against alfa-glucosidase. The docking results showed that ligands having Ortho substituted phenyl ring have good interactions with active site residues and good inhibitory activities as compared to ligands having either Para or Meta substituted phenyl ring except ligand 16 which has the highest docking scores of -12.5 kcal/mol but undergoes para substitution on the phenyl ring and formed hydrogen bond, hydrophobic and electrostatic interactions with the active residues of the enzyme. The QSAR model and molecular docking results agree with each other and give way to the designing of new inhibitors with better activity against alfa-glucosidase.