Synthesis of novel 18 beta-glycyrrhetinic piperazine amides displaying significant in vitro and in vivo antibacterial activities against intractable plant bacterial diseases
Synthesis of novel 18 beta-glycyrrhetinic piperazine amides displaying significant in vitro and in vivo antibacterial activities against intractable plant bacterial diseases
复制标题
新型18β-甘草次哌嗪酰胺的合成，对顽固性植物细菌性疾病具有显着的体外和体内抗菌活性
DOI：
10.1002/ps.5841
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发表时间：
2020
影响因子：
4.1
通讯作者：
Yang Song
中科院分区：
文献类型：
--
作者：
Xiang Meng;Song Ying-Lian;Ji Jin;Zhou Xiang;Liu Li-Wei;Wang Pei-Yi;Wu Zhi-Bing;Li Zhong;Yang Song
背景针对植物细菌性病害的农用化学品数量有限，促使我们研究具有新作用方式的创新抗菌替代品。值得注意的是，制造剧烈的凋亡诱导剂来控制病原菌的繁殖应该是控制植物细菌性病害的可行方法。为了实现这一目标，我们基于天然生物活性成分18β-甘草次酸构建了一系列新型18β-甘草次哌嗪酰胺，以评估其体外和体内抗菌活性以及对测试病原体的诱导细胞凋亡行为。结果筛选结果表明，这些设计的化合物对两种臭名昭著的病原体（Xanthomonas oryzaepv.oryzae和X）具有极高的生物活性。柑橘轴突变种。化合物 A3 和 B1 的生物效应凸显了这一结论，相关 EC50 值为 2.28 和 0.93 μg mL–1。体内试验证实了其在防治水稻白叶枯病方面的前瞻性应用，在 200 μg mL–1 浓度下，控制效率在 50.57–53.70% 范围内。特别是，目标化合物可以诱导受试病原体产生过量的活性氧（ROS），从而在极低的药物浓度（≤10μgmL–1）下产生强烈的细胞凋亡作用。这一发现与扫描电子显微镜模式中观察到的 ROS 增强荧光图像和病原体形态变化一致。结论考虑到这些特征，我们预计这些新型哌嗪定制的 18β-甘草次酸杂合体可以为通过激活细胞凋亡机制来对抗细菌感染提供可感知的见解。据报道，新型 18β-甘草次哌嗪酰胺对植物病原体米黄单胞菌 (Xanthomonas oryzaepv.oryzae) 和 X.柑橘轴突变种。从目标化合物引发的显着的细胞凋亡行为提出了可能的细胞凋亡机制。 © 2020 中国化工学会
BACKGROUNDThe limited amount of agrochemicals targeting plant bacterial diseases has motivated us to study innovative antibacterial surrogates with fresh modes of action. Notably, fabrication of violent apoptosis inducers to control the reproduction of pathogenic bacteria should be a feasible way to control plant bacterial diseases. To achieve this aim, we constructed a series of novel 18β‐glycyrrhetinic piperazine amides based on the natural bioactive ingredient 18β‐glycyrrhetinic acid to evaluate thein vitroandin vivoantibacterial activity and induced apoptosis behaviors on tested pathogens.RESULTSScreening results suggested that these designed compounds were extremely bioactive against two notorious pathogens,Xanthomonas oryzaepv.oryzaeandX. axonopodispv.citri. This conclusion was highlighted by the biological effects of compounds A3and B1, affording the related EC50values of 2.28 and 0.93 μg mL–1.In vivotrials confirmed the prospective application for managing rice bacterial blight disease with control efficiency within 50.57–53.70% at 200 μg mL–1. In particular, target compounds could induce the generation of excessive reactive oxygen species (ROS) in tested pathogens, subsequently leading to a strong apoptotic effect at a very low drug concentration (≤ 10 μg mL–1). This finding was consistent with the observed ROS‐enhanced fluorescent images and morphological changes of pathogens from scanning electron microscopy patterns.CONCLUSIONGiven these features, we anticipate that these novel piperazine‐tailored 18β‐glycyrrhetinic hybrids can provide an perceptible insight for fighting bacterial infections by activation of the apoptosis mechanism.Novel 18β‐glycyrrhetinic piperazine amides were reported to have excellent antibacterial efficacy toward phytopathogensXanthomonas oryzaepv.oryzaeandX. axonopodispv.citri. A possible apoptosis mechanism was proposed from the remarkable apoptotic behaviors triggered by target compounds. © 2020 Society of Chemical Industry