Novel indolyl linked para-substituted benzylidene-based phenyl containing thiazolidienediones and their analogs as α-glucosidase inhibitors: synthesis, in vitro, and molecular docking studies

Abstract

Synthesis of indolyl linked benzylidene-based para-substituted phenyl containing thiazolidinediones and acyclic analogs of isoxazolidinediones—a cyclic analog of thiazolidinedione (4a–7b) in an effort to develop novel α-glucosidase inhibitors in the management of hyperglycemia for the treatment of type 2 diabetes is reported. The structure of all the novel synthesized compounds was confirmed through the spectral studies (LC-MS, 1H-NMR, 13C-NMR, FT-IR). Comparative evaluation of these compounds revealed that the compound 5b showed maximum inhibitory potential against α-amylase and α-glucosidase giving an IC50 value of 0.51 ± 0.01 µM. Furthermore, binding affinities in terms of G score values and hydrogen bond interactions between all the synthesized compounds and the amino acid (AA) residues in the active site of the protein (PDB code: 3TOP) to that of acarbose (standard drug) were explored with the help of molecular docking studies. Compound 5b was considered as promising candidate of this series.