Design and synthesis of new 1,2,3-triazole/benzimidazole hybrids using Click reaction: antibacterial evaluation, molecular docking, and DFT analysis

Abstract

Synthesis of innovative 1,2,3-triazole/ benzimidazole hybrids via click reaction. The structure of the synthesized compounds was confirmed based on their spectral data via FT-IR, 1 H-NMR, 13 C-NMR and elemental analysis. The studied compounds were further subjected to molecular docking in the active site of two particular proteins DNA gyrase B (4duh) and the multidrug transporter AcrB (4dx5), Lipinski's rule, and Swiss ADMET filter, which showed that compound 4b exhibits high GI absorption and favorable drug-likeness profiles along with superior binding affinities compared to the reference drug. Furthermore, all of the synthesized compounds were evaluated as antibiotic systems against Pseudomonas aeruginosa, Staphylococcus aureus , and Candida albicans . The results indicate that the designed compounds 4a–c possess enhanced antibacterial activity, with compound 4b demonstrating the most promising efficacy. Density functional theory (DFT) calculations were presented to investigate the prospective thermodynamic stability, molecular geometry, frontier molecular orbitals energy gap, and molecular electrostatic potential mapping of the synthesized compounds.