Synthesis and Evaluation of Colchicine C-Cyclic AmineDerivatives as Potent Anti-Biofilms Agents AgainstMethicillin-Resistant Staphylococcus aureus.

BACKGROUND/OBJECTIVES: The elimination of bacterial biofilm formation is an effective strategy against bacterial infections. The objective was to design 27 colchicine C-ring modified amine derivatives and evaluate their inhibitory activities against the biofilms of MRSA USA300. METHODS: Design 27 colchicine C-ring modified amine derivatives. Evaluate their inhibitory activities against MRSA USA300 biofilms. Conduct antibacterial or synergistic antibacterial experiments. Research the phenotypic mechanisms related to biofilm-related genes icaA and agrA. RESULTS: The experiments showed that most compounds in this series exhibited varying degrees of biofilm inhibitory activity (with inhibition rates ranging from 7.72% to 40.79%). Further verification through antibacterial or synergistic antibacterial experiments revealed that the compounds with biofilm-inhibiting effects (compounds 7b-11b) generally had certain antibacterial activities (MICs = 16-32 μg/mL) or synergistic antibacterial effects (FICIs < 0.5). Furthermore, through in-depth research on their phenotypic mechanisms (i.e., research on biofilm-related mechanisms), it was found that the compounds with antibacterial or synergistic antibacterial properties could inhibit the formation of biofilms by affecting the regulation of the biofilm-related genes icaA and agrA. CONCLUSIONS: The designed colchicine C-ring modified amine derivatives showed potential in inhibiting MRSA biofilms, and their antibacterial or synergistic antibacterial properties are related to the regulation of biofilm-related genes icaA and agrA, demonstrating inhibitory activity against MRSA.