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

•A novel series of 2-chloro pyridine-based thiosemicarbazones (3a-m) was synthesized.•Characterization of (3a-m) was done by 1H NMR, 13C NMR and mass spectrometric analysis.•Probed for inhibition potential as α-glucosidase inhibitors.•Compound 3m displayed highest inhibition activity with IC50 value of 4.10 ± 0.16 µM.•Molecular docking studies were performed to find the binding mode of most potent inhibitor. 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.