Work

Identification of CH2-linker modified desfluoroquinolone-aminopyrimidine hybrids to combat antibiotic-resistant gram-positive bacteria

Year: 2025

Type: article

Abstract: The increasing prevalence of antibiotic-resistant bacterial infections has emerged as a major public health crisis, necessitating an urgent need for the development of new antimicrobial agents. In this manuscript, structural modifications were conducted on the CH 2 linker of the antibacterial desfluoroquinolone-aminopyrimidine hybrids that we had previously obtained, resulting in compounds A7 , B1 , and D6 . These three compounds exhibited potent activity against a panel of antibiotic-resistant Gram-positive bacteria, including fluoroquinolone-resistant Staphylococcus aureus , linezolid-resistant Staphylococcus aureus , vancomycin-intermediate Staphylococcus aureus (VISA), and vancomycin-resistant Enterococcus faecium . Particularly, despite their structural similarity to classical quinolones , compounds A7 , B1 , and D6 exhibited no cross-resistance with ciprofloxacin . Additionally, the difluorinated CH 2 -linker modified compound demonstrated enhanced metabolic stability. These promising results encourage us to move forward to the next phase of structural optimization, with a specific focus on reducing mammalian cytotoxicity.

Source: Bioorganic Chemistry

DOI: 10.1016/j.bioorg.2025.108496