Synthesis and antibacterial evaluation of novel cationic chalcone derivatives possessing broad spectrum antibacterial activity
Synthesis and antibacterial evaluation of novel cationic chalcone derivatives possessing broad spectrum antibacterial activity
复制标题
新型广谱抗菌阳离子查耳酮衍生物的合成及抗菌评价
DOI：
10.1016/j.ejmech.2017.12.009
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发表时间：
2018-01-01
影响因子：
6.7
通讯作者：
Qin, Shangshang
中科院分区：
文献类型：
--
作者：
Chu, Wen-Chao;Bai, Peng-Yan;Qin, Shangshang
迫切需要鉴定具有新机制的新抗生素，以对抗抗生素耐药性细菌。本文设计并合成了一系列模拟阳离子抗菌肽基本性质的查尔酮衍生物。对金黄色葡萄球菌、粪肠球菌、大肠杆菌、沙门氏菌等药物敏感菌以及临床分离的耐甲氧西林沙门氏菌的抗菌活性。金黄色葡萄球菌（MRSA）、产KPC-2和产NDM-1的碳青霉烯类耐药肠杆菌科。代表性化合物5a（MIC：1 μ g/mL，针对S.金黄色葡萄球菌，0.5 μ g/mL对MRSA）和5g（MIC：0.5 μ g/mL对S.金黄色葡萄球菌，0.25 μ g/mL，抗MRSA）对革兰氏阳性和革兰氏阴性细菌，包括耐药物种MRSA、KPC和NDM都显示出良好的杀菌活性。这些膜活性抗菌化合物被证明有效地减少细菌生物膜中的活细胞计数，并且不会诱导细菌产生耐药性。此外，这些代表性分子在合适的浓度下对哺乳动物细胞表现出可忽略的毒性。综合结果表明，这一系列的阳离子查尔酮衍生物对细菌感染具有潜在的治疗作用。(C)2017 Elsevier Masson SAS。All rights reserved.
There is an urgent need to identify new antibiotics with novel mechanisms that combat antibiotic resistant bacteria. Herein, a series of chalcone derivatives that mimic the essential properties of cationic antimicrobial peptides were designed and synthesized. Antibacterial activities against drug-sensitive bacteria, including Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Salmonella enterica, as well as clinical multiple drug resistant isolates of methicillin-resistant S. aureus (MRSA), KPC-2-producing and NDM-1-producing Carbapenem-resistant Enterobacteriaceae were evaluated. Representative compounds 5a (MIC: 1 mu g/mL against S. aureus, 0.5 mu g/mL against MRSA) and 5g (MIC: 0.5 mu g/mL against S. aureus, 0.25 mu g/mL against MRSA) showed good bactericidal activity against both Gram-positive and Gram-negative bacteria, including the drug-resistant species MRSA, KPC and NDM. These membrane-active antibacterial compounds were demonstrated to reduce the viable cell counts in bacterial biofilms effectively and do not induce the development of resistance in bacteria. Additionally, these representative molecules exhibited negligible toxicity toward mammalian cells at a suitable concentration. The combined results indicate that this series of cationic chalcone derivatives have potential therapeutic effects against bacterial infections. (C) 2017 Elsevier Masson SAS. All rights reserved.