Design and Synthesis of Androgen Receptor Antagonists with Bulky Side Chains for Overcoming Antiandrogen Resistance

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• 作者：Jinming Zhou ; Guoyan Geng ; Qingwen Shi ; Francoise Sauriol ; Jian Hui Wu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：September 10, 2009
• 年：2009
• 卷：52
• 期：17
• 页码：5546-5550
• 全文大小：799K
• 年卷期：v.52,no.17(September 10, 2009)
• ISSN：1520-4804

文摘

Incorporation of curcumin and β-ionone into one chemical entity led to identification of a novel antiandrogen with two bulky side chains, 6, which is a pure antagonist of the wild-type and the T877A, W741C, and H874Y mutated androgen receptors (AR), showing no cross-reactivity with progesterone receptor and low micromolar cytotoxicity in LNCaP, PCa-2b, 22Rv1, and C4-2B prostate cancer cells. Molecular modeling indicates 6 adopts a “Y”-shape conformation and forms multiple hydrogen bonds with AR backbone.