Formononetin derivatives containing benzyl piperidine: A brand new, highly efficient inhibitor targeting Xanthomonas spp,Journal of Advanced Research

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Formononetin derivatives containing benzyl piperidine: A brand new, highly efficient inhibitor targeting Xanthomonas spp
Journal of Advanced Research ( IF 11.4 ) Pub Date : 2024-09-02 , DOI: 10.1016/j.jare.2024.08.039
Miaohe Zhang ₁ , Shuang Feng ₁ , Junrong Song ₂ , Xianghui Ruan ₃ , Wei Xue ₃

Affiliation

Introduction

Plant bacterial diseases take an incalculable toll on global food security. The indiscriminate use of chemical synthetic pesticide not only facilitates pathogen resistance of pathogenic bacteria, but also poses a major threat to human health and environmental protection. Therefore, it is of great economic value and scientific significance to develop a new antibacterial drug with environmental friendliness and unique mechanism of action.

Objectives

To design and synthesize formononetin derivatives based on natural products, evaluate their in vitro and in vivo antibacterial activities and elucidate the mechanisms involved.

Methods

The synthesis was carried out by classical active group splicing method. The antibacterial activities were evaluated using turbidimetry and pot experiments. The antibacterial mechanism was further investigated using scanning electron microscopy (SEM), virulence factors, defense enzymes activities, proteomics and metabolomics.

Results

40 formononetin derivatives containing benzyl piperidine were designed and synthesized. The antibacterial results demonstrated that H32 exhibited the most potent inhibitory effect against Xanthomonas oryzae pv. Oryzae (Xoo) with the EC₅₀ of 0.07 μg/mL, while H6 displayed the highest inhibitory activity against Xanthomonas axonopodis pv. Citri (Xac) with the EC₅₀ of 0.24 μg/mL. Furthermore, the control efficacy of H32 against rice bacterial leaf blight (BLB) and H6 against citrus canker (CC) was validated through pot experiments. SEM, virulence factors and host enzyme activities assay indicated that H32 could not only reduce the virulence of Xoo, but also activate the activities of defense enzymes and improve the disease resistance of host plants. The proteomics and metabolomics analysis demonstrated that H32 could inhibit the synthesis of branched-chain amino acids, make Xoo cells in a starvation state, inhibit its proliferation, weaken its virulence and reduce its colonization and infection of host cells.

Conclusion

Formononetin derivatives containing benzyl piperidine could be used as potentially effective inhibitors against Xanthomonas spp.

中文翻译：

含有苄基哌啶的 Formononetin 衍生物：一种靶向黄单胞菌属的全新高效抑制剂

介绍

植物细菌病害对全球粮食安全造成了不可估量的损失。乱用化学合成农药不仅助长了病原菌的病原菌耐药性，而且对人类健康和环境保护构成了重大威胁。因此，开发一种环境友好、作用机制独特的新型抗菌药物具有重要的经济价值和科学意义。

目标

为了设计和合成基于天然产物的 formononetin 衍生物，评价其体外和体内抗菌活性并阐明所涉及的机制。

方法

采用经典的活性基团剪接法进行合成。使用比浊法和罐实验评估抗菌活性。使用扫描电子显微镜（SEM）、毒力因子、防御酶活性、蛋白质组学和代谢组学进一步研究抗菌机制。

结果

设计合成了 40 种含有苄基哌啶的 formononetin 衍生物。抗菌结果表明，H32 对米黄单胞菌 pv 表现出最有效的抑制作用。水稻 （Xoo）的 EC₅₀ 为 0.07 μg/mL，而 H6 对轴突黄单胞菌 pv 的抑制活性最高。Citri （Xac），EC₅₀ 为 0.24 μg/mL。此外，通过盆栽试验验证了 H32 对水稻细菌性叶枯病（BLB）和 H6 对柑橘溃疡病（CC）的防治效果。SEM、毒力因子和寄主酶活性测定表明，H32 不仅可以降低Xoo 的毒力，还可以激活防御酶的活性，提高寄主植物的抗病性。蛋白质组学和代谢组学分析表明，H32 可以抑制支链氨基酸的合成，使 Xoo 细胞处于饥饿状态，抑制其增殖，减弱其毒力，减少其对宿主细胞的定植和感染。