Computational design and sonochemical synthesis of triazolo benzimidazole derivatives as an antimicrobial agent

Abstract A novel series of disubstituted 1,2,3-triazolo-benzimidazole derivatives (8a-8 g) was efficiently synthesized via copper-catalyzed azide-alkyne cycloaddition (CuAAC) under ultrasonic irradiation, achieving up to 95% yields in 55 min at room temperature. This green sonochemical protocol significantly outperformed conventional methods, yielding high-purity products, as confirmed by FT-IR, 1 H/ 13 C NMR, and Mass spectrometry. In vitro antimicrobial assays revealed potent activity against Gram-positive ( S. aureus , B. cereus ) and Gram-negative ( S. typhimurium , E. coli ) strains, with compounds 8a , 8c and 8d outperforming tetracycline in several cases (zones up to 29 mm). Molecular docking against the Cro repressor (PDB: 1LMB) showed strong binding affinities (-5.07 to -5.67 kcal/mol), with 8a forming key H-bonds to DC29 and hydrophobic contacts to DG14. In silico ADME profiling confirmed drug-likeness (no Lipinski violations, bioavailability score 0.55) and low toxicity, whereas DFT analysis highlighted the high reactivity of 8c (ΔE gap = 1.998 eV). SAR studies underscored the role of 2,4-dimethyl/dinitro substitutions in enhancing broad-spectrum potency, positioning these hybrids as promising antimicrobial leads. Graphical Abstract