Synthesis and bioactivities study of new antibacterial peptide mimics: The dialkyl cationic amphiphiles
Synthesis and bioactivities study of new antibacterial peptide mimics: The dialkyl cationic amphiphiles
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新型抗菌肽模拟物二烷基阳离子两亲物的合成及生物活性研究
DOI：
10.1016/j.ejmech.2017.10.044
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发表时间：
2018
影响因子：
6.7
通讯作者：
Liu Hong-Min
中科院分区：
文献类型：
--
作者：
Zhang En;Bai Peng-Yan;Cui De-Yun;Chu Wen-Chao;Hua Yong-Gang;Liu Qin;Yin Hai-Yang;Zhang Yong-Jie;Qin Shangshang;Liu Hong-Min
由致病菌引起的传染病的出现十分普遍。因此，迫切需要加强开发具有高抑菌活性和低细胞毒性的新型抗菌药物。合成了一系列具有两个相同长度的亲脂烷基链和一个非肽酰胺键的新型二烷基阳离子两亲体，并对革兰氏阳性菌和革兰氏阴性菌进行了抗菌活性测试。合成的特定化合物对金黄色葡萄球菌、E。粪,E。coliandS。以及耐甲氧西林等耐药物种的临床分离株。产kpc和产ndm -1的耐碳青霉烯肠杆菌科（CRE）。例如，最佳化合物4对所有菌株的MIC值在0.5 ~ 2 μg/mL之间。此外，这些小分子作为杀菌剂迅速发挥作用，并主要通过细菌膜的渗透和去极化发挥作用。重要的是，这些化合物很难诱导细菌产生耐药性，并且有可能对抗耐药细菌。因此，这些化合物可以开发成一类新的抗菌肽模拟物，用于抗革兰氏阳性和革兰氏阴性细菌，包括耐药菌株。
The emergence of infectious diseases caused by pathogenic bacteria is widespread. Therefore, it is urgently required to enhance the development of novel antimicrobial agents with high antibacterial activity and low cytotoxicity. A series of novel dialkyl cationic amphiphiles bearing two identical length lipophilic alkyl chains and one non-peptidic amide bond were synthesized and tested for antimicrobial activities against both Gram-positive and Gram-negative bacteria. Particular compounds synthesized showed excellent antibacterial activity toward drug-sensitive bacteria such asS. aureus,E. faecalis,E. coliandS. enterica, and clinical isolates of drug-resistant species such as methicillin-resistantS. aureus(MRSA), KPC-producing and NDM-1-producing carbapenem-resistant Enterobacteriaceae (CRE). For example, the MIC values of the best compound4granged from 0.5 to 2 μg/mL against all these strains. Moreover, these small molecules acted rapidly as bactericidal agents, and functioned primarily by permeabilization and depolarization of bacterial membranes. Importantly, these compounds were difficult to induce bacterial resistance and can potentially combat drug-resistant bacteria. Thus, these compounds can be developed into a new class of antibacterial peptide mimics against Gram-positive and Gram-negative bacteria, including drug-resistant bacterial strains.