Benzo[d]imidazole anchored oxadiazole derivatives: synthesis, characterization, biological evaluation, in silico docking and ADME-T analysis

Abstract

A novel series of 1,2,4-oxadiazoles based on benzo[d]imidazole-1,3,4-oxadiazole fused 1,2,4-oxadiazoles, were synthesised. The proposed chemical structures of the novel hybrids were confirmed by a variety of spectroscopic methods, including HRMS, NMR (¹H/¹³C), and infrared. The antibacterial properties of these compounds showed that compound 8b (37 ± 1.20 mm) and compound 8i (6.9 ± 1.01 µM) had the highest zone of inhibition (ZI) and lowest minimum inhibitory (MIC) values against S. aureus ATCC 29213, which was verified by in silico evaluation. Compound 8f exhibited considerably better antibacterial activity (31 ± 0.19 mm) against S. epidermidis ATCC 12228, and scaffold 8f showed a significantly higher antibacterial effect (31 ± 0.19 mm) against S. pyogenes ATCC 19615 compared to moxifloxacin (29 ± 0.16 mm). Finally, in silico research that includes molecular modelling also validates an in vitro investigation and explains the strong binding pattern of 8b, 8f, 8i, and 8k against E. coli Topoisomerase IV (PDB: 3FV5) and S. aureus GyrB (PDB: 4URN). Extending our exploration, an analysis of the ADME-Tox profiling confirmed the safe use of these newly synthesized scaffolds, paving the way for promising therapeutic applications in the field of antimicrobial therapy.