水杨酸类防腐剂对人和大鼠17β-羟基类固醇脱氢酶1的抑制作用：三维定量构效关系和硅对接分析

IF 2.5 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-06-30 DOI:10.1016/j.jsbmb.2025.106823

Huiqian Zhang , Jiayi He , Xiuwei Shen , Congcong Wen , Yubin Xu , Feilu Wang , Shaowei Wang , Ren-shan Ge , Xiaoheng Li

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引用次数: 0

摘要

胎盘含有17β-羟基类固醇脱氢酶1 (17β-HSD1)，这是一种将雌酮转化为雌二醇的关键酶。水杨酸盐作为防腐剂广泛使用，可能对17β-HSD1具有抑制作用，但其抑制强度和构效关系尚不清楚。本研究评估了13种结构不同的水杨酸盐，确定了人类和大鼠17β-HSD1的有效抑制剂。水杨酸薄荷酯对人（IC50: 5.23 μM）和大鼠（IC50: 14.85 μM）的抑制作用最强。抑制作用与分子量、体积、碳链长度和LogP呈负相关。机制研究显示两种物种的混合/非竞争性抑制。3D-QSAR和分子对接突出了酶活性位点的疏水、范德华和氢键相互作用。关键的结构特征，包括碳链长度和取代基模式，决定了抑制效力。这些发现澄清了SAR，并提示水杨酸盐作为内分泌干扰物的潜力。

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Suppression of human and rat 17β-hydroxysteroid dehydrogenase 1 by salicylate preservatives: 3D quantitative structure-activity relationship and in silico docking analysis

The placenta contains 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1), an enzyme critical for converting estrone to estradiol. Salicylates, widely used as preservatives, may inhibit 17β-HSD1, but their inhibitory strength and structure-activity relationships (SAR) remain unclear. This study evaluated 13 structurally diverse salicylates, identifying potent inhibitors of human and rat 17β-HSD1. Menthyl salicylate showed the strongest inhibition in humans (IC₅₀: 5.23 μM) and rats (IC₅₀: 14.85 μM). Inhibition correlated negatively with molecular weight, volume, carbon chain length, and LogP. Mechanistic studies revealed mixed/noncompetitive inhibition in both species. 3D-QSAR and molecular docking highlighted hydrophobic, van der Waals, and hydrogen-bonding interactions at the enzyme’s active site. Key structural features, including carbon chain length and substituent patterns, determined inhibitory potency. These findings clarify SAR and suggest salicylates' potential as endocrine disruptors.

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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.