New Efforts toward Aminothiazolylquinolones with Multitargeting Antibacterial Potential.

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