含二硫键的1,3,4-噁二唑和1,2,4-三唑衍生物的合成、抗菌活性及机制研究
收稿日期: 2023-11-22
修回日期: 2023-12-31
网络出版日期: 2024-02-20
基金资助
国家自然科学基金(22007022); 国家自然科学基金(32360689); 国家自然科学基金(22364008); 国家自然科学基金(32260694); 国家自然科学基金(21867004); 贵州省自然科技基金(ZZK[2021]034); 贵州省教育厅科技拔尖人才计划(2022075)
Synthesis, Antibacterial Activity and Mechanism Research of 1,3,4-Oxadiazole and 1,2,4-Triazole Derivatives Containing Disulfide Bond
Received date: 2023-11-22
Revised date: 2023-12-31
Online published: 2024-02-20
Supported by
National Natural Science Foundation of China(22007022); National Natural Science Foundation of China(32360689); National Natural Science Foundation of China(22364008); National Natural Science Foundation of China(32260694); National Natural Science Foundation of China(21867004); Guizhou Provincial Natural Science Foundation(ZZK[2021]034); Top Science and Technology Talent Program of Guizhou Education Department(2022075)
为了探索新的抗菌剂, 设计并合成了一系列含二硫键的1,3,4-噁二唑衍生物(X系列)和1,2,4-三唑衍生物(M系列), 并被用于抗菌活性的评估. 研究发现X系列和M系列都对水稻白叶枯病菌(Xanthomonas oryzae pv. Oryzae, Xoo)表现出不错的抗菌活性. 其中, 3-(5-(异丁基二硫基)-4H-1,2,4-三唑-3-基)-1H-吲哚(M1)对水稻白叶枯病菌表现出强效的抗菌活性, EC50值为(1.51±0.24) μg/mL, 优于噻菌酮[(87.97±4.79) μg/mL]和叶枯唑[(66.88±4.06) μg/mL]的活性. 在水稻活体方面, M1也表现了优于阳性对照药叶枯唑的抗菌活性. M1对水稻的治疗和保护作用分别为42.37%和38.64%, 优于叶枯唑的治疗和保护作用(37.49%和36.55%). 此外, 通过对化合物M1机制的相关研究发现, 化合物M1展示了抑制水稻白叶枯病菌生物膜的形成, 提高水稻白叶枯病菌中活性氧的水平和诱导细菌形态变化的能力. 蛋白质组分析揭示了化合物M1下调了三磷酸腺苷结合盒(ABC)转运蛋白, 影响了水稻白叶枯病菌中的腺嘌呤核苷三磷酸(ATP)分解和磷的输运. 最后实时荧光定量聚合酶链式反应(RT-qPCR)证明, 化合物M1通过下调ABC转运蛋白中的磷酸盐特殊转运系统(pst)系统相关基因来发挥其抗菌作用.
关键词： 二硫键; 水稻白叶枯病菌; 蛋白组学; 三磷酸腺苷结合盒(ABC)转运体
邱雪梅 , 胡伟男 , 王文航 , 覃丽清 , 祝丹雪 , 杨孟芝 , 邵利辉 , 谭画元 , 王钦 , 李洙锐 , 陈丹萍 , 王贞超 . 含二硫键的1,3,4-噁二唑和1,2,4-三唑衍生物的合成、抗菌活性及机制研究[J]. 有机化学, 2024 , 44(6) : 2014 -2026 . DOI: 10.6023/cjoc202311022
In order to explore novel antibacterial agents, a series of newly designed and synthesized 1,3,4-oxadiazole derivatives (series X) and 1,2,4-triazole derivatives (series M) incorporating disulfide bond were subjected to antibacterial activities evaluation. Interestingly, both series X and series M showed good antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo). Among them, 3-(5-(isobutyldisulfaneyl)-4H-1,2,4-triazol-3-yl)-1H-indole (M1) exhibited potent antiba- cterial activity against Xoo, with EC50 value of (1.51±0.24) μg/mL, surpassing those of thiodiazole copper [(87.97±4.79) μg/mL] and bismerthiazol [(66.88±4.06) μg/mL]. In rice plants, compound M1 exhibited superior antibacterial activity to the bismerthiazol. The curative and protective effects of compound M1 on rice were 42.37% and 38.64%, respectively, surpassing the curative and protective effects of bismerthiazol (37.49% and 36.55%). Furthermore, through relevant studies on the mechanism of compound M1, it was demonstrated that compound M1 inhibits the formation of biofilms in Xoo, elevates the level of reactive oxygen species in the bacteria, and induces morphological changes. Proteomic analysis revealed that compound M1 down-regulated the adenosine triphosphate-binding cassette (ABC) transporters, which impacts adenosine triphosphate (ATP) decomposition and phosphorus transport in rice bacterial blight. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) demonstrated that compound M1 was experimentally antibacterial by down-regulating related genes in the phosphate special transport (pst) system of the ABC transporters.
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