摘要
Novel quinazolonthiazoles were designed and synthesized as new potential antimicrobial agents by facile multi-step procedure from o-aminobenzoic acids and 2-acetylthiazole.A series of biological evaluation showed that compound 7d was the most effective quinazolonethiazole with superior activity to reference drugs chloramphenicol and norfloxacin.This active molecule displayed unob-vious bacterial resistance against P.aeruginosa,the low toxicity to normal hepatocytes,suitable pharmacokinetics and drug-likeness.The preliminary biological interaction suggested that quinazolonethiazole 7d might induce bacterial death by disturbing the membrane permeability,whilst preventing bacteria from growth by integrating into DNA and binding with topoisomerase IV.These findings provided significant background for the further development of quinazolonethiazoles as new potential drugs in combating drug-resistant pathogens.
基金
the National Natural Science Foundation of China(Nos.21971212 and 21672173)
the Research Funds for the Central Universities(No.XDJK2020C031)
the China Postdoctoral Science Foundation(No.2019M653821XB)
the Postdoctoral Science Foundation Project of Chongqing Science and Technology Bureau(No.cstc2019jcyj-bshX0124)
the Chongqing Special Foundation for Postdoctoral Research Proposal(No.XmT2018082).
