In vitro Antibacterial Activity of Isopropoxy Benzene Guanidine Against Multidrug-Resistant Enterococci
In vitro Antibacterial Activity of Isopropoxy Benzene Guanidine Against Multidrug-Resistant Enterococci
复制标题
异丙氧基苯胍对多重耐药肠球菌的体外抗菌活性
DOI：
10.2147/idr.s234509
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Zeng, Zhenling
中科院分区：
文献类型：
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作者：
Zhang, Xiufeng;Han, Dongdong;Zeng, Zhenling
背景资料：由于对多种常规抗菌药物的耐药性的出现，细菌感染引起严重的公共卫生危机。特别是，属于"ESKAPE"生物体的多药耐药（MDR）屎肠球菌在世界范围内引起重大问题。因此，迫切需要找到替代疗法。近年来，取代苯胍类化合物已成为合成和药物化学中的先导化合物，目的：研究一种新的取代苯胍类似物异丙氧基苯胍对肠球菌的抗菌活性。对参考菌株和32株临床MDR肠球菌菌株进行了检测。采用微量稀释法和杀菌动力学试验评价其体外抗菌活性。结果：异丙氧基苯胍对参考菌株和耐多药肠球菌均具有较强的杀菌活性。对异丙氧基苯胍的最低抑菌浓度（MIC）范围为1 - 4 μ g/mL。最低杀菌浓度（MBC）约为其MIC值的2 - 8倍。时间杀灭研究表明，异丙氧基苯胍在2xMIC下12小时内对参考菌株和MDR菌株提供了上级杀菌效果。此外，异丙氧基苯胍可以导致产生的膜电位的幅度大幅减少相比，未经处理的cells. Conclusion：本研究突出了强大的杀菌活性的异丙氧基苯胍肠球菌通过破坏细胞膜电位。这些研究结果表明，异丙氧基苯胍可能是一个很好的化学铅，为进一步的药物化学和药物开发，并可用作治疗剂的MDR肠球菌引起的感染性疾病。
Background: Bacterial infections cause a serious public health crisis due to the emergence of resistance towards multiple conventional antibacterial drugs. In particular, multidrug-resistant (MDR) Enterococcus faecium which belongs to "ESKAPE" organisms is causing significant problems worldwide. Hence, there is an urgent need to find alternative therapies. Recently, substituted benzene guanidine compounds have been used as lead structures to discover new promising drugs in both synthetic and medicinal chemistry.Purpose: Here we investigated the antimicrobial activity of a new substituted benzene guanidine analog, isopropoxy benzene guanidine, against Enterococci.Material and methods: The isopropoxy benzene guanidine was synthesized by Guangzhou Insighter Biotechnology Co., Ltd and tested on both reference bacterial strain and 32 clinical MDR Enterococci strains. The in vitro antibacterial activity was evaluated by microdilution method and kill kinetic assays. The potential antibacterial mechanism was measured by fluorescence spectrometry using fluorescent membrane potential probe 3, 3-diethyloxacarbocyanine iodide (DiOC(2) (3)).Results: Isopropoxy benzene guanidine exhibited potent bactericidal activity against both reference strain and MDR Enterococci isolates. The minimum inhibitory concentration (MIC) range for isopropoxy benzene guanidine was 1-4 mu g/mL. Minimum bactericidal concentration (MBC) was about 2-8-fold of its MIC values. Time-kill studies showed that isopropoxy benzene guanidine provided superior bactericidal effect against reference and MDR strains within 12 hrs at 2xMIC. Furthermore, isopropoxy benzene guanidine could cause a large reduction in the magnitude of the generated membrane potential compared to that of the untreated cells.Conclusion: The present study highlights the potent bactericidal activity of isopropoxy benzene guanidine on Enterococci by disrupting the cell membrane potential. These findings demonstrate that isopropoxy benzene guanidine may be a good chemical lead for further medicinal chemistry and pharmaceutical development and could be used as a therapeutic agent for infectious diseases caused by MDR Enterococci.