Synthesis of benzimidazole based hydrazones as non-sugar based α-glucosidase inhibitors: Structure activity relation and molecular docking

Abstract

In search for α-glucosidase inhibitors used in the treatment of diabetes mellitus, a series of unique benzimidazole based hydrazones derivatives were synthesized (5a-5p), which were then investigated for their in vitro α-glucosidase inhibitory potential. The compounds of interest were characterized by modern spectroscopic approaches including CHN, ¹ HNM R, ¹³ CN MR and FTIR. The structure of compound 5n was distinctively authenticated through single crystal X-ray study. All compounds depicted potent enzyme inhibitory potential with IC₅₀ values in the range of 2.25 ± 0.01 to 81.16 ± 0.12 μM except 5n that showed IC₅₀ value of 182.75 ± 0.13 μM. A limited structure-activity correlation demonstrated that substitutions of isatin, aldehydes and ketone in hydrazones moiety had remarkable contribution in the overall activity and that was further supported by molecular docking studies carried out in elucidating the mechanism of binding interaction of these compounds in the catalytic site of α-glucosidase.

Keywords: X-ray crystallography; benzimidazole based hydrazones; diabetes mellitus; molecular docking studies; α-glucosidase inhibitor.