Identification of potential N-substituted 5-benzylidenethiazolidine-2,4‑dione derivatives as α-amylase inhibitors: Computational cum synthetic studies

Abstract

Diabetes mellitus is a chronic metabolic disorder become a major health problem globally associated with social and economic consequences. α-amylase is an endo-amylase enzyme that is responsible for the first starch hydrolysis into shorter oligosaccharides by the breaking of D-(1, 4) glycosidic bonds. Different computational studies have been carried out by many researchers to discover new inhibitors as a target of α-amylase. In this work, we used in-silico based drug designing methods to find out the potential lead compounds from a dataset of 36 thiazolidine-2,4-diones. The pharmacophore mapping analysis was carried out in order to identify the functional feature that are responsible for the activity. The pharmacophore screening results a five feature hypotheses AHRRR _1 that is important for the enzyme inhibition. All newly designed library of 64,800 compounds were spawn from R- group enumeration study, to identify better ligands which showed highest binding affinity towards α-amylase enzyme. Structure-based virtual screening was performed on all the enumerated compounds to identify the lead. In the molecular docking and MM-GBSA study, compound 7a showed highest binding score of −7.722 kcal/mol and the dGBind was found to be -71.65502945 kcal/mol. The in-vitro study showed that compound 7a was the potential compound with IC50 value of 1.9 ± 0.103 µM. The compound 7a found to be to be a promising lead for the discovery of potential α-amylase inhibitors.