Zhang Jing, Battini Narsaiah, Ou Jia-Ming, Zhang Shao-Lin, Zhang Ling, Zhou Cheng-He
Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, P. R. China.
J Agric Food Chem. 2023 Feb 8;71(5):2322-2332. doi: 10.1021/acs.jafc.2c08293. Epub 2023 Jan 26.
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.
为应对畜牧业中日益增长的多重耐药性问题，设计并高效合成了新型抗菌3-(氨基噻唑基)喹诺酮类化合物（ATQs）。生物活性测定表明，α,β-二环己基氨基羰基ATQ和甲基ATQ分别对ATCC 29213和[具体菌株未给出]表现出比参考药物诺氟沙星更好的抗菌性能。值得注意的是，具有低溶血率、可忽略不计的哺乳动物细胞毒性和良好药代动力学性质的高活性ATQ诱导耐药性的趋势较低，且与诺氟沙星具有协同组合作用。初步机制探索表明，代表性的ATQ可抑制生物膜形成并破坏细菌膜完整性，进而与细胞内DNA和DNA回旋酶结合以阻碍细菌DNA复制。ATQ还可诱导过量活性氧的产生并降低细菌代谢以加速细菌死亡。这些结果为3-(氨基噻唑基)喹诺酮类化合物作为治疗动物细菌感染的新型潜在多靶点抗菌剂提供了希望。
