Pyrimidine-conjugated fluoroquinolones as new potential broad-spectrum antibacterial agents

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.

Automated summary

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.