Development of Novel 1,2,3‐Triazole‐Benzoxazole Hybrids as an <i>E. coli</i> DNA Gyrase B Inhibitor: Design, Synthesis, in Silico, and in Vitro Antimicrobial Evaluation

Abstract A novel series of 1,2,3‐triazole‐benzoxazole hybrids were designed and synthesized effectively using Cu alkyne‐azide cycloaddition, as a potential antimicrobial agents. The structures of the newly synthesized scaffolds were identified through 1 H NMR, 13 C NMR, FTIR, elemental analysis, and mass spectra. The bioactive synthesized molecule ( 10a–10n ) were evaluated for its antibacterial and antifungal properties in vitro against P. aeruginosa , E. coli , S . pyogenes, S aureus , A . clavatus , A. niger , and C. albicans . Among the synthesized hybrids, compounds 10g and 10k , which contain 4‐methoxy and 3‐chloro substitutes, had the most potent inhibitory activity against E. coli , with MIC values of 0.12 and 0.11 mM, respectively. Subsequently, in silico docking studies were employed to understand better these molecules' binding affinities and mode of action. The molecular docking studies found that all the synthesized molecules showed good affinities with E. coli DNA GyrB (PDB ID: 5L3J). Molecular dynamics (MD) simulations of 100 ns showed stability of the compound 10g protein–ligand complex throughout the simulation.