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

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:

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

Acknowledgements

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

Term human placenta was obtained from the Second Affiliated Hospital of Wenzhou Medical University and used under the guidance of the Clinical Research Committee of Wenzhou Medical University (Protocol no. 2022-K-81-01).

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2024.2355529.

Additional information

Funding

This work was partially supported by Wenzhou Science and Technology Bureau [Y2023025 to X.L.] and Zhejiang Provincial Health Department [11-CX29 to R.S.G.].