Synthesis of benzimidazoles containing piperazine ring as potential therapeutic agents against diabetes mellitus and antioxidant activities

Abstract

We synthesized a novel 6-(4-substitue-piperazin-1-yl)-2-aryl-1H-benzimidazole derivatives starting from 5-(4-substitue-piperazin-1-yl)-2-nitroaniline with different aldehydes. A quick "onepot" nitro reductive cyclization synthesis employing sodium hydrosulfite as a reagent produced the benzimidazoles efficiently. Moreover, we carried out in vitro evaluations, which included an investigation of their α-amylase and α-glucosidase inhibitory activities, as well as their antioxidant properties. The results demonstrated that all the synthesized analogs exhibited significant inhibition of both α-glucosidase and α-amylase potential between IC50 = 0.85 ± 0.25 - 29.72 ± 0.17 µM and IC50 = 4.75 ± 0.24 - 40.24 ± 0.10 µM, respectively, in comparison to the standard acarbose (IC50 = 14.70 ± 0.11 μM). According to the analysis of the kinetic experiments, most of active compounds inhibit a competitive mechanism. Furthermore, the synthesized analogs showed notable DPPH radical scavenging capabilities against standard butylated hydroxytoluene, with SC50 values ranging from 19.05 ± 0.21 to 80.55 ± 0.45 μM. Additionally, molecular docking experiments revealed the interaction profile of each drug when assessing their dock scores to obtain insight into how each chemical would bind to the α-glucosidase and α-amylase enzymes.