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

<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> In the present study, we investigated the effects of folpet, captan, and captafol on estradiol production and human CYP19A1 activity in JEG-3 cells. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> Folpet, captan, and captafol are potential inhibitors of human CYP19A1.