Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, P.R. China.
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
J Med Chem. 2021 May 13;64(9):5603-5619. doi: 10.1021/acs.jmedchem.0c02059. Epub 2021 Apr 28.
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 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 had rapid bactericidal properties and avoided bacterial resistance. More importantly, compound showed strong antibacterial efficacy against and in murine corneal infection models. This design strategy is expected to provide an effective solution to the antibiotic crisis.
由耐药菌引起的感染严重威胁着人类健康和全球公共健康。因此，迫切需要发现和开发新型抗菌药物来对抗多药耐药菌。在这项研究中，我们通过模拟阳离子抗菌肽的结构和功能设计并合成了一系列新型膜活性补骨脂酚衍生物。最有前途的化合物 对革兰氏阳性菌（最小抑菌浓度，MIC = 1.56-3.125μg/mL）和革兰氏阴性菌（MIC = 3.125μg/mL）均显示出强大的抗菌活性，溶血活性非常弱，细胞毒性低。化合物 具有快速杀菌特性，可避免细菌耐药性。更重要的是，化合物 在小鼠角膜感染模型中对 和 表现出强大的抗菌疗效。这种设计策略有望为抗生素危机提供有效的解决方案。
