数量结构-活动关系
生物信息学
类固醇
对接(动物)
化学
IC50型
姜黄素
酶
羟类固醇脱氢酶
脱氢酶
生物化学
立体化学
药理学
抑制性突触后电位
激素
体外
生物
内分泌学
医学
护理部
基因
作者
Jing He,Zhenling Ji,James H. Sang,Hui Qian,Haiyang Zhang,Hua Liu,Jie Zheng,Si Wang,Ren‐Shan Ge,Xiaoling Li
标识
DOI:10.1080/1062936x.2024.2355529
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI