Plant Natural Flavonoids Against Multidrug Resistant Pathogens.
Plant Natural Flavonoids Against Multidrug Resistant Pathogens.
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DOI：
10.1002/advs.202100749
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Shen J
中科院分区：
文献类型：
--
作者：
Song M;Liu Y;Li T;Liu X;Hao Z;Ding S;Panichayupakaranant P;Zhu K;Shen J
越来越多的多药耐药(MDR)细菌病原体的出现和传播加速了对新抗生素的需求。天然产物是发现抗菌剂的首选化学支架。在这里，从植物中提取的天然黄酮类化合物具有抗多药耐药细菌的潜力。构效关系分析表明，异戊烯基化可调节黄酮类化合物的活性，得到两个化合物：山竹黄素(α-mangotin)和异山梨酮(Ibc)。AMG和IBC不仅显示出对革兰氏阳性菌的快速杀菌活性，而且还恢复了粘菌素对革兰氏阴性菌的敏感性。机理研究通常表明，这类化合物通过不同的作用方式与细菌膜上的磷脂结合，导致质子动力的消散和代谢扰动。在与感染或污染相关的四种模型中，AMG和IBC的有效性被证明。这些结果表明，植物的天然产物可能是一个有希望但被低估的储存库，可以绕过现有的抗生素耐药性。异戊烯基化的黄酮类化合物如α-山竹黄素和异巴巴查尔酮对具有透性外膜的多重耐药的革兰氏阳性和革兰氏阴性病原菌有很好的疗效。α-山竹黄素和异巴巴查尔酮都通过靶向细菌膜磷脂的不同作用模式显示出快速杀菌活性。以膜为靶标的抗菌剂具有快速杀灭时间的作用，但产生耐药性的可能性较小。靶向膜是抗菌治疗的一种替代策略。
The increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens accelerate the desires for new antibiotics. Natural products dominate the preferred chemical scaffolds for the discovery of antibacterial agents. Here, the potential of natural flavonoids from plants against MDR bacteria, is demonstrated. Structure–activity relationship analysis shows the prenylation modulates the activity of flavonoids and obtains two compounds, α‐mangostin (AMG) and isobavachalcone (IBC). AMG and IBC not only display rapid bactericidal activity against Gram‐positive bacteria, but also restore the susceptibility of colistin against Gram‐negative pathogens. Mechanistic studies generally show such compounds bind to the phospholipids of bacterial membrane, and result in the dissipation of proton motive force and metabolic perturbations, through distinctive modes of action. The efficacy of AMG and IBC in four models associated with infection or contamination, is demonstrated. These results suggest that natural products of plants may be a promising and underappreciated reservoir to circumvent the existing antibiotic resistance. Isopentenylated flavonoids such as α‐mangostin and isobavachalcone are efficacious against multidrug‐resistant Gram‐positive and Gram‐negative pathogens with permeabilized outer membrane. Both α‐mangostin and isobavachalcone display rapid bactericidal activities through distinctive modes of action by targeting bacterial membrane phospholipids. Antibacterial agents targeting membrane exert fast time‐killing dynamics with less potential to develop resistance. Targeting membrane is an alternative strategy for antibacterial therapy.
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黄酮：从生物合成到健康益处。
DOI：
10.3390/plants5020027
发表时间：
2016-06-21
期刊：
Plants (Basel, Switzerland)
影响因子：
--
作者：
Jiang N;Doseff AI;Grotewold E
通讯作者：
Grotewold E
DOI：
10.1073/pnas.1611594113
发表时间：
2016-10-11
影响因子：
11.1
作者：
Boll, Joseph M.;Crofts, Alexander A.;Trent, M. Stephen
通讯作者：
Trent, M. Stephen
影响因子：
--
作者：
Farha, Maya A.;Verschoor, Chris P.;Brown, Eric D.
通讯作者：
Brown, Eric D.
影响因子：
64.5
作者：
Kohanski, Michael A.;Dwyer, Daniel J.;Collins, James J.
通讯作者：
Collins, James J.
影响因子：
11.8
作者：
Boucher, Helen W.;Talbot, George H.;Bartlett, John
通讯作者：
Bartlett, John