Membrane-Targeting Amphiphilic Honokiol Derivatives Containing an Oxazole Moiety as Potential Antibacterials against Methicillin-Resistant .

Infections with methicillin-resistant (MRSA) are becoming increasingly serious, making the development of novel antimicrobials urgent. Here, we synthesized some amphiphilic honokiol derivatives bearing an oxazole moiety and investigated their antibacterial and hemolytic activities. Bioactivity evaluation showed that possessed significant antibacterial activity against and MRSA, along with low hemolytic activity. Moreover, exhibited rapid bactericidal properties and was not susceptible to resistance. Mechanistic studies indicated that interacts with phosphatidylglycerol and cardiolipin of bacterial cell membranes, leading to changes in cell membrane permeability and polarization, increased intracellular ROS, and leakage of DNA and proteins, thus accelerating bacterial death. Transcriptome analysis further demonstrated that has membrane-targeting effects, affecting the expression of genes related to cell membranes and ABC transporter proteins. Notably, activity showed that has prominent anti-MRSA efficacy, comparable to vancomycin, and is expected to be a new anti-MRSA drug candidate.