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


ÖZİL M., Khan K. M., BALTAŞ N., Wadood A., Samad A., KAHVECİ B.

Journal of Molecular Structure, vol.1304, 2024 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 1304
  • Publication Date: 2024
  • Doi Number: 10.1016/j.molstruc.2024.137714
  • Journal Name: Journal of Molecular Structure
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Keywords: Antioxidant, Benzimidazole, One-pot, Piperazine, Synthesis, α-amylase, α-Glucosidase
  • Recep Tayyip Erdoğan University Affiliated: Yes

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.