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

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 alpha-amylase and alpha-glucosidase inhibitory activities, as well as their antioxidant properties. The results demonstrated that all the synthesized analogs exhibited significant inhibition of both alpha-glucosidase and alpha-amylase potential between IC50 = 0.85 +/- 0.25 - 29.72 +/- 0.17 mu M and IC50 = 4.75 +/- 0.24 - 40.24 +/- 0.10 mu M, respectively, in comparison to the standard acarbose (IC50 = 14.70 +/- 0.11 mu M). 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 mu M. 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 alpha-glucosidase and alpha-amylase enzymes.