狄氏碳酸杀菌剂抑制了人类和老鼠的芳香酶活性,这取决于结构:3D-QSAR分析和分子模拟
Z Ji1,2,3,4, H Chen5, J I Zheng2,3,4
1Department of Gynecology and Obstetrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
SAR and QSAR in environmental research
|October 30, 2024
概括
在农业中广泛使用的二甲基酸杀菌剂被发现能有效抑制人类和老鼠的芳酶 (CYP19A1). 这些化合物与酶相互作用.
科学领域:
- 生物化学和分子生物学
- 环境毒理学环境毒理学
- 农业科学 农业科学
背景情况:
- 狄氏碳酸杀菌剂在农业中广泛用于疾病控制,影响粮食安全.
- 芳酶 (CYP19A1) 是类固醇生物合成中的关键酶,其抑制可以产生显著的生理效应.
- 了解农业化学品与人类和动物关键酶的相互作用,对于风险评估至关重要.
研究的目的:
- 评估八种迪西奥卡巴酸盐化合物对人类和老鼠芳酶 (CYP19A1) 活性的抑制作用.
- 阐明抑制的机制,并确定关键的分子相互作用.
- 使用计算方法探索结构-活动关系并预测结合模式.
主要方法:
- 进行了酶抑制试验,以确定人类和老鼠CYP19A1.1.的IC50值.
- 进行了动力学研究以描述抑制机制 (混合/非竞争性).
- 在分析中,包括3D-QSAR和分子对接,用于调查结合相互作用.
主要成果:
- 齐内布,马尼布,蒂拉姆和费尔巴姆显示出对人类CYP19A1的强烈抑制,IC50值在2.79至6.04μM之间.
- 迪苏尔菲拉姆,马尼布,齐内布和蒂拉姆是大鼠CYP19A1的强效抑制剂,IC50值从1.90到6.99微米.
- 狄氏碳酸盐作为混合/非竞争性抑制剂,与Cys437残留物有关的血部位结合.
结论:
- 几种dithiocarbamates对人类和老鼠的芳酶 (CYP19A1) 都表现出显著的抑制作用.
- 抑制机制涉及与血结合部位的相互作用,特别是Cys437.
- 这些发现突显了dithiocarbamate杀菌剂的潜在毒理学影响,需要进一步调查.
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