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 and methyl ATQ 17a, respectively, showed better antibacterial
behavior against Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa than reference drug norfloxacin. Notably, highly active ATQ 17a 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 17a 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 17a 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.