Design, Synthesis, and Biological Evaluation of Membrane-Active Bakuchiol Derivatives as Effective Broad-Spectrum Antibacterial Agents.
Hongxia LiJiayong LiuChuan Fa LiuHaizhou LiJiachun LuoShanfang FangYongzhi ChenRongcui ZhongShouping LiuShuimu LinPublished in: Journal of medicinal chemistry (2021)
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 28 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 28 had rapid bactericidal properties and avoided bacterial resistance. More importantly, compound 28 showed strong in vivo antibacterial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa in murine corneal infection models. This design strategy is expected to provide an effective solution to the antibiotic crisis.
Keyphrases
- drug resistant
- multidrug resistant
- acinetobacter baumannii
- public health
- gram negative
- human health
- silver nanoparticles
- staphylococcus aureus
- pseudomonas aeruginosa
- risk assessment
- anti inflammatory
- wound healing
- biofilm formation
- klebsiella pneumoniae
- climate change
- essential oil
- cystic fibrosis
- escherichia coli
- optical coherence tomography
- methicillin resistant staphylococcus aureus