Structure-activity relationship and molecular docking analysis of novel arylhydrazones of imidazodiazabicycloalkanones with antibacterial properties.

A series of arylhydrazones of imidazodiazabicycloalkanones was synthesized via nucleophilic addition of oxazole-5(4H)-one-based arylhydrazones to terminal diamines. Their stability under alkaline conditions was supported by UV-vis spectroscopic studies, simulating environments associated with bacterial growth. Antibacterial screening revealed synthesized compounds exhibited pronounced activity. In particular, 4-Cl phenyl substituted imidazopyrimidinone showed strong inhibitory effects against Staphylococcus aureus 209P, while 4-Br phenyl substituted imidazoimidazolone demonstrated potent activity against Pseudomonas aeruginosa V-31, comparable to kanamycin and tetracycline. A synergistic effect was observed for 4-Cl phenyl substituted imidazopyrimidinone in combination with tetracycline. ADMET analysis indicated good gastrointestinal absorption, moderate-to-high oral bioavailability, and low predicted toxicity for most compounds. Molecular docking studies are in harmony with the experimental findings: 4-Cl phenyl substituted both imidazopyrimidinone and imidazoimidazolone confirmed activity to S. aureus, while 4-Br phenyl substituted imidazodiazabicycloalkanones were active against P. aeruginosa. Overall, this study highlights the potential of selected arylhydrazones as promising leads for the development of novel antibacterial agents with both direct and synergistic activity profiles supported by in vitro and in silico data.