Development of Amphiphilic Coumarin Derivatives as Membrane-Active Antimicrobial Agents with Potent In Vivo Efficacy against Gram-Positive Pathogenic Bacteria.
Rongcui ZhongHaizhou LiHongxia LiShanfang FangJiayong LiuYongzhi ChenShouping LiuShuimu LinPublished in: ACS infectious diseases (2021)
Increases in drug-resistant pathogens are becoming a serious detriment to human health. To combat pathogen infections, a new series of amphiphilic coumarin derivatives were designed and synthesized as antimicrobial agents with membrane-targeting action. We herein report a lead compound, 25, that displayed potent antibacterial activity against Gram-positive bacteria, including MRSA. Compound 25 exhibited weak hemolytic activity and low toxicity to mammalian cells and can kill Gram-positive bacteria quickly (within 0.5 h) by directly disrupting the bacterial cell membranes. Additionally, compound 25 demonstrated excellent efficacy in a murine corneal infection caused by Staphylococcus aureus. These results suggest that 25 has great potential to be a potent antimicrobial agent for treating drug-resistant Gram-positive bacterial infections.
Keyphrases
- drug resistant
- gram negative
- multidrug resistant
- staphylococcus aureus
- acinetobacter baumannii
- human health
- risk assessment
- methicillin resistant staphylococcus aureus
- anti inflammatory
- climate change
- biofilm formation
- stem cells
- mesenchymal stem cells
- cystic fibrosis
- wound healing
- cancer therapy
- pseudomonas aeruginosa
- bone marrow