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, 1HNM R, 13CN 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.

Magnolol and Luteolin Inhibition of α-Glucosidase Activity: Kinetics and Type of Interaction Detected by In Vitro and In Silico Studies

“…Structure-based studies have been performed on the putative binding mode experienced by acarbose, as well as by several series of α-glucosidase inhibitors, based on homology modeling techniques [38][39][40]. Most of them relied on the X-ray crystallographic data of Saccharomyces cerevisiae 1,6-glucosidase as a protein template, including maltose (pdb code = 3A4A) [41] and isomaltose (pdb code = 3AXH) [42] as enzyme substrates.…”

Synthesis, Molecular Docking Studies and ADME Prediction of Some New Albendazole Derivatives as α-Glucosidase Inhibitors

“…Ahmad et al 9 provided an overview about the α-glucosidase inhibitory potential of a variety of benzimidazole derivatives III (Figure 1).…”

Dithiocarbamate derivatives inhibit α‐glucosidase through an apparent allosteric site on the enzyme

“…Recently, the literature has witnessed the identification of a plethora of promising α‐glucosidase inhibitors with novel and diverse chemistry (Ghani, 2020). Some of these include benzimidazole‐based hydrazones (Ahmad et al., 2021), usnic acid derivatives (Nguyen et al., 2021), tri‐amide derivatives (Mohammadi et al., 2021), indole‐based thiadiazole derivatives (Alomari et al., 2021) and novel ursolic acid analogs (Wu et al., 2017). Additionally, a number of dithiocarbamate derivatives conjugated with coumarin moiety have also been studied that exhibit potent inhibition of α‐glucosidase.…”