Evolution and Antibacterial Evaluation of 8-Hydroxy-cycloberberine Derivatives as a Novel Family of Antibacterial Agents Against MRSA.

Twenty-five new derivatives of 8-hydroxycycloberberine () were synthesized and evaluated for their activities against Gram-positive bacteria, taking as the lead. Part of them displayed satisfactory antibacterial activities against methicillin-susceptible (MSSA) and methicillin-resistant (MRSA), as well as vancomycin-intermediate (VISA). Especially, compound displayed an excellent anti-MRSA activity with MICs (minimum inhibitory concentrations) of 0.25⁻0.5 μg/mL, better than that of . It also displayed high stability in liver microsomes and whole blood, and the LD value of over 65.6 mg·kg in mice via intravenous route, suggesting a good druglike feature. The mode of action showed that could effectively suppress topo IV-mediated decatenation activity at the concentration of 7.5 μg/mL, through binding a different active pocket of bacterial topo IV from quinolones. Taken together, the derivatives of constituted a promising kind of anti-MRSA agents with a unique chemical scaffold and a specific biological mechanism, and compound has been chosen for the next investigation.