Development of Membrane-Targeting Fluorescent 2-Phenyl-1-phenanthro[9,10-]imidazole-Antimicrobial Peptide Mimic Conjugates against Methicillin-Resistant .

The escalation of multidrug-resistant bacterial infections, especially infections caused by methicillin-resistant (MRSA), underscores the urgent need for novel antimicrobial drugs. Here, we synthesized a series of amphiphilic 2-phenyl-1-phenanthro[9,10-]imidazole-antimicrobial peptide (AMP) mimic conjugates (-). Among them, compound exhibited excellent antibacterial activity against G+ bacteria and clinical MRSA isolates (MIC = 0.5-2 μg/mL), high membrane selectivity, and low toxicity. Additionally, compared with traditional clinical antibiotics, demonstrated rapid bactericidal efficacy and was less susceptible to causing bacterial resistance. Mechanistic studies revealed that targets phosphatidylglycerol (PG) on bacterial membranes to disrupt membrane integrity, leading to an increase in intracellular ROS and leakage of proteins and DNA, ultimately causing bacterial cell death. Furthermore, possessed good fluorescence properties with potential for further dynamic monitoring of the antimicrobial process. Notably, showed better efficacy against MRSA compared to vancomycin, suggesting its potential as a promising candidate for anti-MRSA medication.