Inhibition of Resveratrol Analogs on Human and Rat 3β-Hydroxysteroid Dehydrogenases: Structure-Activity Relationship and Docking Analysis

被引：0

作者：

Su, Ming ^{[1
,3
]}

Ye, Lei ^{[1
]}

Tang, Yunbing ^{[2
]}

Wang, Shaowei ^{[2
]}

Hu, Zhiyan ^{[1
]}

Li, Huitao ^{[1
]}

Wang, Yiyan ^{[1
]}

Li, Xiaoheng ^{[1
]}

Liu, Yi ^{[2
]}

Ge, Ren-Shan ^{[1
,2
,3
]}

机构：

[1] Department of Anaesthesiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, Wenzhou,325027, China

[2] Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, Wenzhou,325027, China

[3] Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, Zhejiang Province, Wenzhou,325000, China

来源：

Journal of Agricultural and Food Chemistry | 2023年 / 71卷 / 19期

关键词：

This work was supported by Department of Health of Zhejiang Province (11-CX29 to R.S.G.) and Zhejiang Medical Science and Technology Project (2020KY185 to Y.L.);

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Resveratrol and its analogs are phytochemicals. Human 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1) synthesizes steroid hormones for normal pregnancy or promoting cancer metastasis. Whether they inhibit 3β-HSD1 remains unclear. In this study, the inhibitory potency, mode of action, structure-activity relationship, and docking parameters of resveratrol and its analogs on 3β-HSD1 and rat homolog 3β-HSD4 were analyzed. The inhibitory potency of these chemicals on human 3β-HSD1 was 4,4′-dihydroxystilbene (IC50, 3.68 μM) > pinostilbene (8.07 μM) > pinosylvin (10.60 μM) > lunularin (26.84 μM) > resveratrol (30.20 μM) > dihydroresveratrol (>100 μM) = oxyresveratrol (>100 μM) > dihydropinosylvin (ineffective at 100 μM). Resveratrol analogs and metabolites are mixed or competitive inhibitors of human 3β-HSD1. Resveratrol and 4,4′-dihydroxystilbene inhibited progesterone secretion by human JAr cells at ≥1 μM. Resveratrol (IC50, 32.09 μM) and pinosylvin (34.71 μM) significantly inhibited rat placental 3β-HSD4 activity. Docking analysis shows that resveratrol analogs and metabolites bind the steroid-binding sites of human 3β-HSD1 and rat 3β-HSD4 and interact with the catalytic residues Ser125/Thr125 and Tyr155. The negative correlation of LogP and IC50 values for human 3β-HSD1 indicates that lipophilicity of chemicals plays a critical role in the inhibitory effect of chemicals. In conclusion, 4,4′-dihydroxystilbene, pinostilbene, and pinosylvin effectively inhibit human 3β-HSD1 depending on their lipophilicity, thereby acting as potential therapeutic agents. © 2023 American Chemical Society

引用

页码：7566 / 7574

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