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  2. Potent inhibition of human and rat 17β-hydroxysteroid dehydrogenase 1 by curcuminoids and the metabolites: 3D QSAR and in silico docking analysis

Potent inhibition of human and rat 17β-hydroxysteroid dehydrogenase 1 by curcuminoids and the metabolites: 3D QSAR and in silico docking analysis

  • SAR QSAR Environ Res. 2024 May 24:1-24. doi: 10.1080/1062936X.2024.2355529.
J He 1 2 3 Z Ji 1 2 3 J Sang 1 2 3 H Quan 1 2 3 H Zhang 1 2 3 H Lu 4 J Zheng 4 S Wang 4 R S Ge 1 2 3 4 5 X Li 1 2 3 4 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Yuying Children's Hospital, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou, China.
  • 2 Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou, China.
  • 3 Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China.
  • 4 Department of Gynecology and Obstetrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 5 Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, Wenzhou, Zhejiang Province, China.
Abstract

Curcumin, an extensively utilized natural pigment in the food industry, has attracted considerable attention due to its potential therapeutic effects, such as anti-tumorigenic and anti-inflammatory activities. The Enzyme 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) holds a crucial position in oestradiol production and exhibits significant involvement in oestrogen-responsive breast cancers and endometriosis. This study investigated the inhibitory effects of curcuminoids, metabolites, and analogues on 17β-HSD1, a key Enzyme in oestradiol synthesis. Screening 10 compounds, including demethoxycurcumin (IC50, 3.97 μM) and dihydrocurcumin (IC50, 5.84 μM), against human and rat 17β-HSD1 revealed varying inhibitory potencies. These compounds suppressed oestradiol secretion in human BeWo cells at ≥ 5-10 μM. 3D-Quantitative structure-activity relationship (3D-QSAR) and molecular docking analyses elucidated the interaction mechanisms. Docking studies and Gromacs simulations suggested competitive or mixed binding to the steroid or NADPH/steroid binding sites of 17β-HSD1. Predictive 3D-QSAR models highlighted the importance of hydrophobic regions and hydrogen bonding in inhibiting 17β-HSD1 activity. In conclusion, this study provides valuable insights into the inhibitory effects and mode of action of curcuminoids, metabolites, and analogues on 17β-HSD1, which may have implications in the field of hormone-related disorders.

Keywords

17β-hydroxysteroid dehydrogenase 1; 3D-QSAR; BeWo cell; Curcumin derivatives; molecular docking.

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