Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, 250012, China.
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, 250012, China.
Eur J Med Chem. 2019 Dec 15;184:111743. doi: 10.1016/j.ejmech.2019.111743. Epub 2019 Sep 27.
The continuous emergence of drug-resistant bacteria has become a severe threat to the public health. Therefore, the discovery of novel antibacterial mechanisms to combat this jeopardized problem is urgently needed. In the past decades, plenty of new antibacterial modes of action have been discovered continuously, based on which many promising scaffolds have been designed and synthesized. In particular, cationic amphiphilic small-molecules open a door to the new mode of action of bactericidal agents by depolarizing and disturbing the bacteria membrane. The cationic amphiphilic are characterized by high efficacy, resistant-proof, wide-spectrum, and high selectivity toward bacteria. In this review, we summarized recent advances in the discovery of membrane-active small-molecules and their structure-activity relationships (SARs), hoping to provide an evidence for future research and development of new antibacterial agents with new mechanism.
耐药菌的不断出现，已对公众健康构成严重威胁。因此，急需发现新的抗菌机制来应对这一威胁。在过去的几十年中，人们不断发现新的抗菌作用模式，在此基础上设计和合成了许多有前途的骨架。特别是，阳离子两亲小分子通过去极化和扰乱细菌膜，为杀菌剂的新作用模式开辟了道路。阳离子两亲小分子具有高效、耐药、广谱和对细菌高选择性的特点。在这篇综述中，我们总结了近年来在发现膜活性小分子及其结构-活性关系（SAR）方面的进展，希望为未来具有新机制的新型抗菌药物的研究和开发提供依据。
