Fan Jiajia, Li Pengxi, Zhao Fanrong, Zheng Li, Wang Peng, Liu Donghui, Zhou Zhiqiang, Liu Xueke
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, PR China.
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, PR China.
J Hazard Mater. 2025 Mar 5;485:136921. doi: 10.1016/j.jhazmat.2024.136921. Epub 2024 Dec 16.
Ipconazole (IPC) is a chiral triazole fungicide and commonly used for disease control in seeds. This study investigated the bioactivity and potential mechanism of ipconazole against pathogenic microorganisms at the chiral perspective. It explored the accumulation behavior of ipconazole enantiomers within the soil-earthworm system and evaluated its toxic effects on earthworms. Bioactivity evaluation revealed that the bioactivity order of ipconazole against three plant pathogens is (-)-1S,2 R,5S-IPC > rac-IPC > (+)-1R,2S,5R-IPC, and the bioactivity of (-)-1S,2 R,5S-IPC is 34.6-129.5 times higher than that of (+)-1R,2S,5R-IPC. Molecular docking found that (-)-1S,2 R,5S-IPC has a stronger binding affinity for the target protein CYP51 to cause activity differences. Accumulation and metabolism studies revealed that (-)-1S,2 R,5S-IPC is more persistent than that of (+)-1R,2S,5R-IPC, and ipconazole was primarily metabolized into hydroxylated ipconazole through hydroxylation in the soil-earthworm system. Toxicological evaluation found growth inhibitory effects and histopathological damage to earthworms at an exposure concentration of 1.5 mg kg ipconazole. Further investigation indicated that these toxic effects of ipconazole were caused by inducing oxidative damage and influencing the functional gene expression of related growth. These research findings will further enhance the understanding of the activity and risks of ipconazole enantiomers, contributing to the safer use of ipconazole in the agricultural environment.
异康唑（IPC）是一种手性三唑类杀菌剂，常用于种子病害防治。本研究从手性角度研究了异康唑对病原微生物的生物活性及潜在作用机制。探讨了异康唑对映体在土壤 - 蚯蚓系统中的积累行为，并评估了其对蚯蚓的毒性效应。生物活性评价表明，异康唑对三种植物病原菌的生物活性顺序为（-）-1S，2R，5S - IPC＞外消旋体IPC＞（+）-1R，2S，5R - IPC，且（-）-1S，2R，5S - IPC的生物活性比（+）-1R，2S，5R - IPC高34.6 - 129.5倍。分子对接发现（-）-1S，2R，5S - IPC对靶蛋白CYP51具有更强的结合亲和力，从而导致活性差异。积累和代谢研究表明，（-）-1S，2R，5S - IPC比（+）-1R，2S，5R - IPC更持久，在土壤 - 蚯蚓系统中，异康唑主要通过羟基化代谢为羟基异康唑。毒理学评价发现，在异康唑暴露浓度为1.5 mg/kg时，对蚯蚓有生长抑制作用和组织病理学损伤。进一步研究表明，异康唑的这些毒性作用是通过诱导氧化损伤和影响相关生长功能基因表达引起的。这些研究结果将进一步加深对异康唑对映体活性和风险的理解，有助于异康唑在农业环境中的更安全使用。
