Benzimidazole derivatives as β-lactamase inhibitors with antibiofilm activity against Acinetobacter baumannii: in vitro and in silico evaluation

Alheety, Nuaman F.; Raouafi, Noureddine; Alheety, Mustafa A.; Besbes, Rafaâ

doi:10.37652/juaps.2025.162207.1477

	Benzimidazole derivatives as β-lactamase inhibitors with antibiofilm activity against Acinetobacter baumannii: in vitro and in silico evaluation
Journal of University of Anbar for Pure Science
Volume 20, Issue 2, August 2026, Pages 173-186 PDF (5.32 M)
Document Type: Research Paper
DOI: 10.37652/juaps.2025.162207.1477
Authors
Nuaman F. Alheety^* ¹; Noureddine Raouafi²; Mustafa A. Alheety³; Rafaâ Besbes²
¹Analytical Chemistry and Electrochemistry Lab (LR99ES15), Department of Chemistry, Faculty of Science, University of Tunis El Manar, Tunis El Manar, 2092, Tunisia Department of General Science, College of Basic Education-Haditha, University of Anbar, Al Anbar, 31001, Iraq
²Analytical Chemistry and Electrochemistry Lab (LR99ES15), Department of Chemistry, Faculty of Science, University of Tunis El Manar, Tunis El Manar, 2092, Tunisia
³Department of Nursing, Al-Hadi University College, Baghdad, Iraq
Abstract
This study reports the synthesis and characterization of three benzimidazole derivatives, N1, N2, and N 3 , and their evaluation as potential antibacterial agents against multidrug-resistant (MDR) Acinetobacter baumannii. The synthetic pathway began with 2-mercapto-5-nitrobenzimidazole, leading to the intermediate N1, which was subsequently converted into compounds N2 and N3. The structures of all synthesized compounds were confirmed using FTIR and 1H NMR spectroscopy. The in vitro antibacterial activity was evaluated using agar diffusion, minimum inhibitory concentration (MIC) determination, growth-curve analysis, and biofilm inhibition assays. The results showed that all compounds exhibited antibacterial activity, with compound N3 producing the largest inhibition zone, outperforming amikacin and vitamin C, and demonstrating strong antibiofilm activity. Furthermore, molecular docking studies against β-lactamase enzyme (PDB ID: 5L2F) revealed favorable binding affinities for all ligands, with N3 showing the best docking score, −8.239kcal/mol, surpassing that of the reference antibiotic amikacin. These findings suggest that the synthesized benzimidazole derivatives, particularly N3, may represent promising lead candidates for the development of antibacterial and antibiofilm agents against MDR infections.
Keywords
Antibacterial drug design; Benzimidazole derivatives; β-lactamase inhibition; Molecular docking; Multidrug-resistant (MDR) Acinetobacter baumannii

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