Synthesis, in vitro α-glucosidase inhibitory potential and in silico study of 2‑chloro pyridine incorporated thiosemicarbazones

Abstract

Diabetes is a devastating metabolic illness that affects people of all ages and is widespread around the world as a result of the malfunctioning of prior treatment approaches. This work attempts to treat type 2 diabetes mellitus (T2DM) by outlining the design, synthesis, in vitro and in silico assessment of 2-Nicotinaldehyde-based thiosemicarbazones as possible inhibitors of α-glucosidase. The synthesized derivatives 3(a-m) displayed excellent to good inhibitory potential against standard drug acarbose (IC50 = 4.10 ± 0.16 µM to 32.76 ± 0.80 µM. Among these compounds 3m displayed highest inhibition activity with IC50 value of 4.10 ± 0.16 µM. SAR of the derivatives have shown that the compounds with meta substitution displayed better activity than the para substitution. In order to obtain more profound understanding, molecular dynamics, and in silico molecular docking simulations were performed to examine the interactions, stability, orientation, and conformation of the synthesized derivatives inside the α-glucosidase active pocket.