设计、合成及抗菌评价新型 PFK-158 衍生物对耐药菌的抗菌活性。
Design, synthesis, and antibacterial evaluation of PFK-158 derivatives as potent agents against drug-resistant bacteria.
机构信息
School of Pharmacy, Jinzhou Medical University, Jinzhou 121001, PR China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
出版信息
Bioorg Med Chem Lett. 2021 Jun 1;41:127980. doi: 10.1016/j.bmcl.2021.127980. Epub 2021 Mar 22.
Infections caused by antibiotic resistant bacteria are a major health concern throughout the world. It is well known that PFK-158 can enhance the antibacterial effect of polymyxin, but its own anti-bactericidal effect is rarely discussed. In order to investigate the anti-bactericidal effect of PFK-158 and its derivatives, PFK-158 and 35 derivatives were designed, synthesized, and evaluated for their antibacterial activities. Compounds A1, A3, A14, A15 and B6 exhibited potent antibacterial effect against both clinical drug sensitive and resistant Gram-positive bacteria, and they are 2-8 folds more potent than levofloxacin against Methicillin-resistant staphylococcus epidermidis (MRSE). A significant synergistic effect of these compounds and polymyxin against drug-resistant Gram-negative bacteria, which is similar to PFK-158 was also observed. The result can provided a new and broader prospect for the development of new medicine against drug-resistant bacteria.
在全球范围内，抗生素耐药菌引起的感染是一个主要的健康关注点。众所周知，PFK-158 可以增强多黏菌素的抗菌作用，但很少讨论其自身的杀菌作用。为了研究 PFK-158 及其衍生物的杀菌作用，设计、合成了 PFK-158 和 35 个衍生物，并对它们的抗菌活性进行了评价。化合物 A1、A3、A14、A15 和 B6 对临床药敏和耐药革兰氏阳性菌均表现出很强的抗菌作用，对耐甲氧西林表皮葡萄球菌（MRSE）的活性比左氧氟沙星强 2-8 倍。这些化合物与多黏菌素对耐药革兰氏阴性菌的协同作用也很显著，与 PFK-158 相似。该结果为开发针对耐药菌的新药提供了新的、更广阔的前景。
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