Design, Synthesis, and Biological Evaluation of Membrane-Active Bakuchiol Derivatives as Effective Broad-Spectrum Antibacterial Agents.

Infections caused by drug-resistant bacteria seriously endanger human health and global public health. Therefore, it is urgent to discover and develop novel antimicrobial agents to combat multidrug-resistant bacteria. In this study, we designed and synthesized a series of new membrane-active bakuchiol derivatives by biomimicking the structure and function of cationic antibacterial peptides. The most promising compound displayed potent antibacterial activity against both Gram-positive bacteria (minimum inhibitory concentration, MIC = 1.56-3.125 μg/mL) and Gram-negative bacteria (MIC = 3.125 μg/mL), very weak hemolytic activity, and low cytotoxicity. Compound had rapid bactericidal properties and avoided bacterial resistance. More importantly, compound showed strong antibacterial efficacy against and in murine corneal infection models. This design strategy is expected to provide an effective solution to the antibiotic crisis.