环姜黄素作为一种潜在的治疗剂，能有效抑制人芳香化酶。
Cyclocurcumin potently inhibits human aromatase as a potential therapeutic agent.
作者信息
Lu Han, Zheng Jingyi, Hu Chunnan, He Jiayi, Wang Shaowei, Chen Zhuoqi, Wang Yiyan, Li Huitao, Ge Ren-Shan, Tang Yunbing, Ying Yingfen
机构信息
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, Wenzhou Medical University, Zhejiang Province, China.
Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, Wenzhou Medical University, Zhejiang Province, China.
出版信息
J Steroid Biochem Mol Biol. 2025 Mar;247:106672. doi: 10.1016/j.jsbmb.2024.106672. Epub 2024 Dec 31.
Curcuminoids, including curcumin and its derivatives, show potent inhibition of aromatase (CYP19A1), crucial for estradiol synthesis and breast cancer metastasis. Our study evaluated the efficacy and mechanism of 10 curcuminoids and their metabolites against human and rat CYP19A1 using placental microsomes, revealing species-specific IC values. Cyclocurcumin (IC, 4.43 μM) and curcumin (IC, 3.49 μM) were the most effective inhibitors for human and rat CYP19A1, respectively. These compounds acted as mixed or competitive inhibitors, reducing estradiol production in human BeWo cells. Docking analysis showed that curcuminoids interact with CYP19A1 active site, forming a hydrogen bond with Met374. 3D-QSAR analysis highlighted the importance of hydrogen bonding in inhibition. A negative correlation was observed between the pKa values and IC values for human CYP19A1. A positive correlation was observed between the lowest binding energy and IC values for human CYP19A1. These findings underscore the potential of curcuminoids as therapeutic agents against breast cancer.
姜黄素类化合物，包括姜黄素及其衍生物，对芳香化酶（CYP19A1）具有强效抑制作用，而芳香化酶对雌二醇合成和乳腺癌转移至关重要。我们的研究使用胎盘微粒体评估了10种姜黄素类化合物及其代谢产物对人和大鼠CYP19A1的疗效及作用机制，揭示了种属特异性的半数抑制浓度值。环姜黄素（半数抑制浓度为4.43 μM）和姜黄素（半数抑制浓度为3.49 μM）分别是对人和大鼠CYP19A1最有效的抑制剂。这些化合物作为混合型或竞争性抑制剂，可减少人BeWo细胞中雌二醇的产生。对接分析表明，姜黄素类化合物与CYP19A1活性位点相互作用，与甲硫氨酸374形成氢键。三维定量构效关系分析突出了氢键在抑制作用中的重要性。观察到人类CYP19A1的pKa值与半数抑制浓度值之间呈负相关。观察到人类CYP19A1的最低结合能与半数抑制浓度值之间呈正相关。这些发现强调了姜黄素类化合物作为乳腺癌治疗药物的潜力。
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