期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 73, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2022.128885
关键词
Pyrimidine; Fluoroquinolone; Antibacterial; DNA
资金
- National Natural Science Foundation of China [21971212]
- Key Project of Innovation Research 2035 Pilot Plan of Southwest University [SWU-XDZD22007]
- Post- doctoral Science Foundation Project of Chongqing Science and Technology Bureau [cstc2019jcyj-bshX0124]
- China Postdoctoral Science Foundation [2019M653821XB]
- Chongqing Special Foundation for Postdoctoral Research Proposal [XmT2018082]
- Natural Science Foundation of Chongqing [cstc2019jcyj-msxmX0202]
Pyrimidine-conjugated fluoroquinolones demonstrated effective antibacterial activity against drug-resistant strains, with compound 1c exhibiting broad-spectrum antibacterial potency and low cytotoxicity. Compound 1c showed superior antibacterial activity against Enterococcus faecalis and exhibited lower trend for the development of drug-resistance compared to norfloxacin and ciprofloxacin. Further analysis revealed that compound 1c could induce ROS accumulation and interact with DNA, leading to bacterial death.
Pyrimidine-conjugated fluoroquinolones were constructed to cope with the dreadful resistance. Most of the target pyrimidine derivatives effectively suppressed the growth of the tested strains, especially, 4-aminopyrimi-dinyl compound 1c showed a broad antibacterial spectrum and low cytotoxicity and exhibited superior anti-bacterial potency against Enterococcus faecalis with a low MIC of 0.25 mu g/mL to norfloxacin and ciprofloxacin. The active compound 1c with fast bactericidal potency could inhibit the formation of biofilms and showed much lower trend for the development of drug-resistance than norfloxacin and ciprofloxacin. Further exploration revealed that compound 1c could prompt ROS accumulations in bacterial cells and interact with DNA to form a DNA -1c complex, thus facilitating bacterial death. ADME analysis indicated that compound 1c possessed favorable drug-likeness and promising pharmacokinetic properties. These results demonstrated that pyrimidine-conjugated fluoroquinolones held hope as potential antibacterial candidates and deserve further study.
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