Development of a nitric oxide-releasing cephalexin-based hybrid compound for enhanced antimicrobial efficacy and biofilm disruption.

ABSTRACT: Biofilm formation on medical devices and the rise of antibiotic resistance have undermined conventional antibiotics such as cephalexin (CEX), which is effective against Gram-positive infections but has limited activity against Gram-negative pathogens and biofilms. To overcome these limitations, we developed a hybrid nitric oxide (NO)-releasing conjugate (SNAP_CEX) by covalently attaching the NO donor S-nitroso-N-acetylpenicillamine (SNAP) to CEX. SNAP_CEX exhibited a sustained NO release profile over 30 days, indicating enhanced stability compared to SNAP's rapid degradation, even though the Griess assay showed NO release from SNAP over 30 days. The hybrid maintained strong antibacterial activity against Staphylococcus aureus (S. aureus; MIC₅₀ = 7 μM

SUBMITTER: Kumar S 

PROVIDER: S-EPMC12435586 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature