Details

Autor(en) / Beteiligte

• He, J.
• Ji, Z.
• Sang, J.
• Quan, H.
• Zhang, H.
• Lu, H.
• Zheng, J.
• Wang, S.
• Ge, R.S.
• Li, X.

Titel

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

Ist Teil von

• SAR and QSAR in environmental research, 2024-06, Vol.35 (6), p.433-456

Ort / Verlag

England: Taylor & Francis

Erscheinungsjahr

2024

Quelle

Taylor & Francis

Beschreibungen/Notizen

• 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 (IC 50 , 3.97 μM) and dihydrocurcumin (IC 50 , 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.