A new route to the synthesis of 2-hydrazolyl-4-thiazolidinone hybrids, evaluation of α-glucosidase inhibitory activity and molecular modeling insights

One of the multifactorial worldwide health syndromes is diabetes mellitus which is increasing at a disturbing rate. The inhibition of α-glucosidase, an enzyme that catalyzes starch hydrolysis in the intestine, is one helpful therapeutic approach for controlling hyperglycemia related to type-2 diabetes. To discover α-glucosidase inhibitors, some 2-hydrazolyl-4-thiazolidinone hybrids (<b>3a-e</b>) were synthesized from new one-pot reaction procedures. Next, their chemical structures were confirmed by ¹H NMR, ¹³C NMR, and FT-IR spectra, and elemental analysis technique. Then, the α-glucosidase inhibitory activity of the titled compounds was evaluated. Among them, derivatives <b>3b</b> and <b>3c</b> revealed the highest activity against α-glucosidase compared to acarbose as a drug. Enzyme kinetic studies of the most active derivative (<b>3b</b>) indicated a competitive inhibition. Finally, molecular modeling studies were accomplished to describe vital interactions of the most potent compounds (<b>3b</b> and <b>3c</b>) with the α-glucosidase enzyme.