Disrupting Biofilms and Enhancing Antibacterial Activity via Novel Ciprofloxacin-Lipid Conjugates

To overcome the ever-growing global challenge of antibiotic resistance, we have synthesized a series of 17 ciprofloxacin-lipophilic (CIP-LIP) conjugates using a carbodiimide reagent. The antibacterial efficacy of these conjugates was evaluated in vitro against two bacterial strains: Staphylococcus aureus (ATCC 29213) and Pseudomonas aeruginosa (PAO1). Notably, three synthesized conjugates, 9, 19, and 21 (MIC = 0.06 μg/mL), exhibited 2-fold higher antibacterial activity than CIP (MIC = 0.125 μg/mL) against S. aureus. Conjugate 11 emerged as the most potent against P. aeruginosa, with an MIC of 2 μg/mL. Additionally, conjugates 9 and 11 displayed significant antibiofilm activity against both P. aeruginosa and S. aureus. Compound 9 exhibited no cytotoxic effect against both HepG2 and J774A at concentrations of 100 μg/mL. Collectively, these findings open new avenues for the development of lipophilic-based CIP conjugates as modified ciprofloxacin derivatives for targeting bacterial biofilms and DNA gyrase.