Investigation on Diabetes and Mechanism of Thiadiazole–Schiff Base as Therapeutic Hybrid: Enzyme Activity and Molecular Docking Studies

Abstract In an approach to combat diabetes mellitus, a widely spread noncommunicable disease (NCDs), a novel series of compounds (1–18) containing substituted thiadiazole bearing Schiff base derivative was synthesized and evaluated against enzymes causing diabetes mellitus. The results confirm that most of the compounds were found active and exhibit excellent biological activity as compared to the standard drug acarbose. Their minimal inhibitory concentrations for both enzymes lie in a range between 18.10 ± 0.30 and 2.10 ± 0.30 µM for α‐amylase and 19.20 ± 0.30 µM and 2.70 ± 0.80 µM for α‐glucosidase in contrast with the reference drug having IC 50 of 4.30 ± 0.40 and 5.10 ± 0.70 µM. The most active analogs were found to be 2 , 4 , 7 , 9, and 15 , which displayed few‐fold higher potency than the control drug. Structural evaluation was conducted using various spectroscopic techniques such as 1 H NMR, 13 C NMR and HREIMS for all the synthesized derivatives, and in silico molecular docking studies of all the active analogs confirms the interactions between ligand and binding proteins.