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

• Published in: Journal of molecular structure 2024-05, Vol.1304, p.137714, Article 137714
• Main Authors: Özil, Musa, Khan, Khalid Mohammed, Baltaş, Nimet, Wadood, Abdul, Samad, Abdus, Kahveci, Bahittin
• Format: Article
• Language: English
• Subjects: Antioxidant; Benzimidazole; One-pot; Piperazine; Synthesis; α-amylase; α-Glucosidase
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.137714

•A novel series of benzimidazole derivatives was successfully synthesized.•The benzimidazoles were effectively synthesized by a rapid ‘onepot’ nitro reductive cyclization reaction using sodium dithionite as reagent.•The compounds were evaluated for their in vitro inhibitory activity against α-amylase and α-glucosidase, as well as their antioxidant properties.•Moreover, the kinetics studies revealed highly favorable binding energies and a.competitive inhibition mode.•Molecular docking studies were conducted to determine the binding mode of the most potent inhibitor. 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. [Display omitted]