福美双、克菌丹和敌菌丹对 JEG-3 细胞中人芳香酶的影响。

Effects of Folpet, Captan, and Captafol on Human Aromatase in JEG-3 Cells.

机构信息

Center for Reproductive Medicine, Taizhou People's Hospital, The Fifth Hospital Affiliated Nantong University, Taizhou, China.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Pharmacology. 2018;102(1-2):81-87. doi: 10.1159/000484171. Epub 2018 Jun 28.

DOI:10.1159/000484171

PMID:29953993

Abstract

BACKGROUND

Estradiol, produced by aromatase (CYP19A1), is very important for reproduction. Folpet, captan, and captafol belong to the phthalimide class of fungicides. They are used to protect the leaves of plants or fruits. They could be endocrine disruptors and may disrupt CYP19A1 activity.

METHODS

In the present study, we investigated the effects of folpet, captan, and captafol on estradiol production and human CYP19A1 activity in JEG-3 cells.

RESULTS

Folpet, captan, and captafol decreased estradiol production in JEG-3 cells in a concentration-dependent manner. Folpet, captan, and captafol inhibited human CYP19A1 with inhibitory concentration (IC50) values of 3.55, 10.68, and 1.14 μmol/L respectively. These chemicals competitively inhibited human CYP19A1. Molecular docking simulation analysis showed that they tended to bind to the steroid-binding pocket of the CYP19A1. However, the required concentrations may not be relevant to the negligible systemic exposures in humans to these chemicals.

CONCLUSION

Folpet, captan, and captafol are potential inhibitors of human CYP19A1.

摘要

背景

雌激素由芳香酶（CYP19A1）产生，对生殖非常重要。福美双、克菌丹和敌菌丹属于邻苯二甲酰亚胺类杀菌剂。它们用于保护植物的叶子或果实。它们可能是内分泌干扰物，可能会干扰 CYP19A1 的活性。

方法

在本研究中，我们研究了福美双、克菌丹和敌菌丹对 JEG-3 细胞中雌二醇产生和人 CYP19A1 活性的影响。

结果

福美双、克菌丹和敌菌丹以浓度依赖的方式降低 JEG-3 细胞中雌二醇的产生。福美双、克菌丹和敌菌丹对人 CYP19A1 的抑制浓度（IC50）值分别为 3.55、10.68 和 1.14 μmol/L。这些化学物质竞争性抑制人 CYP19A1。分子对接模拟分析表明，它们倾向于结合 CYP19A1 的甾体结合口袋。然而，所需的浓度可能与这些化学物质在人体中的微不足道的全身暴露无关。