Design, synthesis of griseofamine A derivatives and development of potent antibacterial agents against MRSA

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA), one of the most important multidrug-resistant bacteria in clinic, has become a serious global health issue. In this study, we designed and synthesized a series of griseofamine A derivatives and evaluated their antibacterial profiles. In vitro assays found that compound 9o10 showed a remarkable improvement of antibacterial activity toward MRSA (MIC = 0.0625 μg/mL), compared with griseofamine A (MIC = 8 μg/mL) and vancomycin (MIC = 0.5 μg/mL) with low hemolysis and cytotoxicity. Its rapid bactericidal property was also confirmed by time-kill curve assay. Furthermore, compound 9o10 displayed weak drug resistance frequency. In in vivo experiment, compound 9o10 exhibited more potent antibacterial efficacy than vancomycin and excellent biosafety (LD