氮杂异黄酮类似物作为植物雌激素模拟物的设计与合成。

Design and synthesis of azaisoflavone analogs as phytoestrogen mimetics.

作者信息

Gim Hyo Jin, Li Hua, Jung So Ra, Park Yong Joo, Ryu Jae-Ha, Chung Kyu Hyuck, Jeon Raok

机构信息

Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, 52 Hyochangwon-Gil, Yongsan-Ku, Seoul 140-742, Republic of Korea.

School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do, Republic of Korea.

出版信息

Eur J Med Chem. 2014 Oct 6;85:107-18. doi: 10.1016/j.ejmech.2014.07.030. Epub 2014 Jul 15.

DOI:10.1016/j.ejmech.2014.07.030

PMID:25078314

Abstract

A series of azaisoflavone analogs were designed and synthesized and their transactivation activities and binding affinities for ERα and ERβ were investigated. Among these compounds, 2b and 3a were the most potent with 6.5 and 1.1 μM of EC50, respectively. Molecular modeling study showed putative binding modes of the compound 3a in the active site of ERα and ERβ, which were similar with that of genistein and provided insight of the effect of N-alkyl substitution of azaisoflavones on ERβ activity. Also, a biphasic effect of azaisoflavone analogs on MCF-7 cell growth depending on their concentrations was investigated.

摘要

设计并合成了一系列氮杂异黄酮类似物，并研究了它们对雌激素受体α（ERα）和雌激素受体β（ERβ）的反式激活活性及结合亲和力。在这些化合物中，2b和3a活性最强，其半数有效浓度（EC50）分别为6.5 μM和1.1 μM。分子模拟研究表明化合物3a在ERα和ERβ活性位点的假定结合模式，这与染料木黄酮的结合模式相似，并为氮杂异黄酮的N-烷基取代对ERβ活性的影响提供了见解。此外，还研究了氮杂异黄酮类似物对MCF-7细胞生长的浓度依赖性双相效应。