Benzophenone UV-filters: Inhibition on human and rat 17β-hydroxysteroid dehydrogenase 1 - insights from 3D-QSAR and docking studies

IF 2.7 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-03-21 DOI:10.1016/j.jsbmb.2025.106739

Zhuoqi Chen , Chaochao Gong , Shaowei Wang , Han Lu , Yang Zhu , Ren-shan Ge , Yunbing Tang , Yingfen Ying

{"title":"Benzophenone UV-filters: Inhibition on human and rat 17β-hydroxysteroid dehydrogenase 1 - insights from 3D-QSAR and docking studies","authors":"Zhuoqi Chen , Chaochao Gong , Shaowei Wang , Han Lu , Yang Zhu , Ren-shan Ge , Yunbing Tang , Yingfen Ying","doi":"10.1016/j.jsbmb.2025.106739","DOIUrl":null,"url":null,"abstract":"<div><div>Benzophenone (BP) UV-filters have been extensively used for the prevention of UV-induced adverse effects in personal care products. Their potential to interfere with steroidogenesis in the female reproductive system remains uncertain. 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) facilitates the conversion of estrone to estradiol, playing a key role in estrogen activation. This study delves into the effects of eleven BPs on human and rat 17β-HSD1, while also analysing the 3D-quntitative structure-activity relationship (3D-QSAR) and the underlying mechanisms. The inhibitory potency of inhibiting human placental 17β-HSD1 was found to be in the order of BP-2 (IC<sub>50</sub>, 11.42 μM) > BP-1 (14.17 μM) > BP-4 (49.05 μM) > BP-6 (63.49 μM) = BP-8 (63.46 μM) > others. BP-1 and BP-2 markedly inhibited estradiol secretion by human placental BeWo cells at ≥ 1 μM. In contrast, the inhibitory strength of suppressing rat ovarian 17β-HSD1 activity was found to be in the order of BP-2 (IC<sub>50</sub>, 13.33 μM) > BP-1 (15.09 μM) > BP-4 (22.68 μM) > BP-12 (31.12 μM) > BP-3 (97.11 μM) > BP (119.99 μM) > others. Mode action analysis revealed that these BP compounds acted as mixed inhibitors of both human and rat 17β-HSD1. The introduction of a 4-hydroxyl substitution in the benzene ring was found to markedly increase the inhibitory potency against human and rat 17β-HSD1. BP-1 and BP-2 demonstrated the ability to penetrate human BeWo cells and inhibit estradiol secretion at ≥ 1 μM. Docking analysis revealed that the 2-hydroxyl group of BP-1 and BP-2 forms a hydrogen bond with catalytic residue Ser142 of human 17β-HSD1. 3D-QSAR pharmacophore analysis showed that there are hydrophobic regions and hydrogen bond donor can interact with BPs. In conclusion, this study establishes that BP-2 is the most potent inhibitors of human 17β-HSD1 among the BPs under investigation, highlighting a significant difference in the structure-activity relationship.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"250 ","pages":"Article 106739"},"PeriodicalIF":2.7000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Steroid Biochemistry and Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960076025000676","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Benzophenone (BP) UV-filters have been extensively used for the prevention of UV-induced adverse effects in personal care products. Their potential to interfere with steroidogenesis in the female reproductive system remains uncertain. 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) facilitates the conversion of estrone to estradiol, playing a key role in estrogen activation. This study delves into the effects of eleven BPs on human and rat 17β-HSD1, while also analysing the 3D-quntitative structure-activity relationship (3D-QSAR) and the underlying mechanisms. The inhibitory potency of inhibiting human placental 17β-HSD1 was found to be in the order of BP-2 (IC₅₀, 11.42 μM) > BP-1 (14.17 μM) > BP-4 (49.05 μM) > BP-6 (63.49 μM) = BP-8 (63.46 μM) > others. BP-1 and BP-2 markedly inhibited estradiol secretion by human placental BeWo cells at ≥ 1 μM. In contrast, the inhibitory strength of suppressing rat ovarian 17β-HSD1 activity was found to be in the order of BP-2 (IC₅₀, 13.33 μM) > BP-1 (15.09 μM) > BP-4 (22.68 μM) > BP-12 (31.12 μM) > BP-3 (97.11 μM) > BP (119.99 μM) > others. Mode action analysis revealed that these BP compounds acted as mixed inhibitors of both human and rat 17β-HSD1. The introduction of a 4-hydroxyl substitution in the benzene ring was found to markedly increase the inhibitory potency against human and rat 17β-HSD1. BP-1 and BP-2 demonstrated the ability to penetrate human BeWo cells and inhibit estradiol secretion at ≥ 1 μM. Docking analysis revealed that the 2-hydroxyl group of BP-1 and BP-2 forms a hydrogen bond with catalytic residue Ser142 of human 17β-HSD1. 3D-QSAR pharmacophore analysis showed that there are hydrophobic regions and hydrogen bond donor can interact with BPs. In conclusion, this study establishes that BP-2 is the most potent inhibitors of human 17β-HSD1 among the BPs under investigation, highlighting a significant difference in the structure-activity relationship.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Steroid Biochemistry and Molecular Biology 生物-内分泌学与代谢

CiteScore

8.60

自引率

2.40%

发文量

113

审稿时长

46 days

期刊介绍： The Journal of Steroid Biochemistry and Molecular Biology is devoted to new experimental and theoretical developments in areas related to steroids including vitamin D, lipids and their metabolomics. The Journal publishes a variety of contributions, including original articles, general and focused reviews, and rapid communications (brief articles of particular interest and clear novelty). Selected cutting-edge topics will be addressed in Special Issues managed by Guest Editors. Special Issues will contain both commissioned reviews and original research papers to provide comprehensive coverage of specific topics, and all submissions will undergo rigorous peer-review prior to publication.