姜黄素是一种在食品工业中广泛使用的天然色素，由于其潜在的治疗作用（例如抗肿瘤和抗炎活性）而引起了广泛的关注。 17β-羟基类固醇脱氢酶 1 (17β-HSD1) 在雌二醇的产生中起着至关重要的作用，并且在雌激素反应性乳腺癌和子宫内膜异位症中发挥着重要作用。本研究调查了姜黄素、代谢物和类似物对 17β-HSD1（雌二醇合成中的关键酶）的抑制作用。筛选 10 种化合物，包括去甲氧基姜黄素（IC50，3.97μM）和二氢姜黄素（IC50，5.84μM），对人和大鼠 17β-HSD1 具有不同的抑制效力。这些化合物以≥5-10μM抑制人BeWo细胞中雌二醇的分泌。 3D 定量构效关系 (3D-QSAR) 和分子对接分析阐明了相互作用机制。对接研究和 Gromacs 模拟表明，与 17β-HSD1 的类固醇或 NADPH/类固醇结合位点存在竞争性或混合性结合。预测 3D-QSAR 模型强调了疏水区域和氢键在抑制 17β-HSD1 活性中的重要性。总之，这项研究为类姜黄素、代谢物和类似物对 17β-HSD1 的抑制作用和作用方式提供了有价值的见解，这可能对激素相关疾病领域产生影响。

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.