Structure-activity relationship and in silico docking analysis of dicarboximide fungicides on 17β-hydroxysteroid dehydrogenase 1 of human, rat, and pig.

IF 6.2 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Ecotoxicology and Environmental Safety Pub Date : 2024-12-13 DOI:10.1016/j.ecoenv.2024.117529
Huiqian Chen, Sailing Chen, Yunbing Tang, Yingfen Ying, Shaowei Wang, Yang Zhu, Yiyan Wang, Ren-Shan Ge, Ping Duan
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Abstract

Dicarboximide fungicides, including captafol, captan, cyclohexylthiophthalimide, folpet, and procymidone, represent a distinct category of fungicides. 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) catalyzes the conversion of estrone to estradiol in mammals. Yet, the impact of these fungicides on 17β-HSD1 activity remains unknown. In this study, we investigated their inhibition using human placental cytosols, rat and pig ovarian cytosols. Our observations revealed that dicarboximide fungicides significantly inhibited human 17β-HSD1 activity. Among them, captan showed the strongest potency, with its IC50 of 1.28 μM, whereas procymidone had an IC50 of 100.71 μM. However, both rat and pig 17β-HSD1 enzymes were less sensitive to the inhibition of these fungicides compared to the human enzyme, with captan displaying an IC50 of 5.65 μM for the rat enzyme and 7.36 μM for the pig enzyme. Correlation analysis indicated a positive correlation between IC50 values and LogP. Docking analysis revealed that these fungicides bound to cofactor or between the steroid and cofactor binding sites. The dithiothreitol treatment demonstrated that the formation of irreversible bonds between dicarboximide fungicides and the cysteine residues played a key role in the inhibition of 17β-HSD1 activity. In conclusion, dicarboximide fungicides inhibit 17β-HSD1 depending on lipophilicity, species, and cysteine residue interactions.

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二甲酰亚胺类杀菌剂对人、大鼠和猪的 17β- 羟基类固醇脱氢酶 1 的结构-活性关系和硅对接分析
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来源期刊
CiteScore
12.10
自引率
5.90%
发文量
1234
审稿时长
88 days
期刊介绍: Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.
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