Synthesis and antibacterial evaluations of novel vancomycin analogues targeting bacteria membrane to combat Gram-negative infections.

Vancomycin is primarily used to treat severe infections caused by Gram-positive bacteria and is often considered as the last-resort therapy in the life-threatening situation. However, it is inherently ineffective against Gram-negative bacteria. Herein, we report the design, synthesis, and biological evaluation of novel vancomycin analogues incorporated with lipophilic cationic groups.

2,4-Diacetylphloroglucinol (DAPG) derivatives rapidly eradicate methicillin-resistant staphylococcus aureus without resistance development by disrupting membrane.

Methicillin-resistant Staphylococcus aureus (MRSA) causes severe public health challenges throughout the world, and the multi-drug resistance (MDR) of MRSA to antibiotics necessitates the development of more effective antibiotics. Natural 2,4-diacetylphloroglucinol (DAPG), produced by Pseudomonas, displays moderate inhibitory activity against MRSA. A series of DAPG derivatives was synthesized and evaluated for their antibacterial activities, and some showed excellent activities (MRSA MIC = 0.