Substituted bisbenzimidazole derivatives as multiple targeting agents to treat Alzheimer's disease, diabetes, and microbial infections


Algul O., Mete B., TÜRKMENOĞLU B., Saglamtas R., ALAGÖZ M. A., Dogen A., ...More

Journal of Molecular Structure, vol.1323, 2025 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 1323
  • Publication Date: 2025
  • Doi Number: 10.1016/j.molstruc.2024.140800
  • 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: Antimicrobial activity, Bisbenzimidazole, Enzyme inhibition, Molecular docking, Structure-activity relationship
  • Erzincan Binali Yildirim University Affiliated: Yes

Abstract

This study presents the synthesis and bioactivity screening of a series of substituted bisbenzimidazoles (3a–l), assessed for their inhibitory effects on α-glycosidase, α-amylase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), as well as their antibacterial activities and metal chelation properties. Compound 3e exhibited the most significant inhibitory activity against intestinal α-glycosidase and α-amylase, showing IC50 values of 15.51 µM and 18.18 µM, respectively. All bisbenzimidazole derivatives demonstrated significant inhibitory activities, with Ki values between 0.99 and 2.98 nM for AChE and 0.40 to 2.18 nM for BChE. Antimicrobial analyses revealed significant antibacterial efficacy in compounds 3c and 3f, with IC50 values ranging from 10.75 to 12.83 μg/μL. This article presents a thorough evaluation of the pharmacological activities associated with bisbenzimidazole compounds 3a–l. To validate experimental results, selected compounds exhibiting notable enzyme inhibitory potential were subjected to molecular docking studies, which demonstrated their binding interactions within the active sites of target enzymes. Molecular dynamics simulation studies were carried out for 100 ns to determine the stability of the compounds in target proteins. During the simulation, it was observed that 3 h, 3 g, 3l, and 3e were stable in 4EY7, 4BDS, 3TOP, and 2QV4, respectively. Compounds 3 h, 3 g, 3e, and 3l have been identified as promising candidates for the inhibition of AChE, BChE, α-glycosidase, and α-amylase, respectively.