New Efforts toward Aminothiazolylquinolones with Multitargeting Antibacterial Potential

• DOI: 10.1021/acs.jafc.2c08293
• Publication Date: 2023-01-26T15:19:08Z
• Authors: Jing Zhang; Narsaiah Battini; Jia-Ming Ou; Shao-Lin Zhang; Ling Zhang; Cheng-He Zhou
• Keywords: Mammals; 0301 basic medicine; Staphylococcus aureus; 0303 health sciences; 03 medical and health sciences; Bacteria; Animals; DNA; Microbial Sensitivity Tests; Quinolones; 3. Good health; Norfloxacin; Anti-Bacterial Agents

New antibacterial 3-(aminothiazolyl)quinolones (ATQs) were designed and efficiently synthesized to counteract the growing multidrug resistance in animal husbandry. Bioactive assays manifested that N,N-dicyclohexylaminocarbonyl ATQ 10e methyl 17a, respectively, showed better behavior against Staphylococcus aureus ATCC 29213 Pseudomonas aeruginosa than reference drug norfloxacin. Notably, highly active 17a with low hemolysis, negligible mammalian cytotoxicity, good pharmacokinetic properties displayed trends induce synergistic combinations Preliminary mechanism exploration implied representative could inhibit formation of biofilms destroy bacterial membrane integrity, further binding intracellular DNA gyrase hinder replication. also production excess reactive oxygen species reduce metabolism accelerate death. These results provided a promise for as new potential multitargeting agents treat infection animals.