BackgroundPlant pathogenic bacteria and fungi had a wide impact on various crops and caused serious economic losses. Compared to traditional antibiotics and fungicides, alkaloids are noteworthy for their significant biological activities. Tetrahydrocarbazole (THCz) was widely present in many indole alkaloids and had various pharmacological activities. This study used Fischer indole synthesis method and fragment splicing strategy to design and synthesize a novel drug like chemical entity based on THCz alkaloid guidance, evaluated the antimicrobial activities of these derivatives against plant pathogenic bacteria and fungi and discussed the structure–activity relationship.ResultsAmong these derivatives, compound KZa‐17 displayed good antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri, Pseudo‐monas sollamacearum and Erwinia aroideae. The MIC90 values were 3.12, 1.56, 6.25, 12.5 μg/mL, respectively, which were better than the positive control drugs thiodiazole copper and bismerthiazol. The results of in vivo antibacterial activity test showed that the protective effect of compound KZa‐17 on rice at 200 μg/mL was 32.76%, which was better than that of thiodiazole copper (24.73%). The biochemical experiments showed that compound KZa‐17 could inhibit biofilm formation of Xoo, reduce drug resistance and pathogenicity of bacteria, damage cell membrane integrity, increase permeability, and cause oxidative stress damage.ConclusionMost of the newly synthesized derivatives based on THCz alkaloid guidance showed favorable antimicrobial effects. In particular, compound KZa‐17 can be used as a candidate lead compound for further structural optimization and development. © 2024 Society of Chemical Industry.

中文翻译：

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针对植物病原真菌和细菌的新型四氢咔唑衍生物的设计、合成和抗菌活性评价


背景植物病原菌和真菌对各种作物产生广泛影响，造成严重的经济损失。与传统的抗生素和杀菌剂相比，生物碱因其显着的生物活性而值得注意。四氢咔唑 （THCz） 广泛存在于许多吲哚生物碱中，并具有多种药理活性。本研究使用 Fischer 吲哚合成方法和片段剪接策略，基于 THCz 生物碱指导设计合成了一种新型药物样化学实体，评价了这些衍生物对植物病原菌和真菌的抗菌活性，并讨论了构效关系。结果在这些衍生物中，化合物 KZa-17 对米黄单胞菌 pv 表现出良好的抗菌活性。水稻 （Xoo），Xanthomonas axonopodis pv.citri、Pseudo‐monas sollamacearum 和 Erwinia aroideae。MIC90 值分别为 3.12 、 1.56 、 6.25 、 12.5 μg/mL，优于阳性对照药物硫代二唑铜和比斯噻唑。体内抗菌活性试验结果显示，化合物 KZa-17 在 200 μg/mL 时对水稻的保护作用为 32.76%，优于硫代二唑铜（24.73%）。生化实验表明，化合物 KZa-17 可以抑制 Xoo 的生物膜形成，降低细菌的耐药性和致病性，破坏细胞膜完整性，增加通透性，并引起氧化应激损伤。结论大多数基于 THCz 生物碱指导的新合成衍生物显示出良好的抗菌效果。特别是，化合物 KZa-17 可用作进一步结构优化和开发的候选先导化合物。© 2024 化工学会.