16α取代雌二醇与雌激素受体ER结合活性的量子化学研究

QUANTUM CHEMISTRY STUDY ON THE RELATIVE BINDING AFFINITIES OF 16α-SUBSTITUTED ESTRADIOL DERIVATIVES

应用从头算方法(HF/STO-3G)计算了25个16α取代雌二醇的电子结构,研究了化合物的电子结构与活性(RelativeBindingAffinities)的定量关系,结果表明:(1)前线轨道集中在雌二醇衍生物的活性中心A环、3-OH和17-OH上;(2)支持了17-OH、3-OH与受体形成氢键的观点;(3)16α位引入取代基对17-OH产生空间位阻.取代基体积增大,空间位阻增大,活性降低;(4)16α位的取代基与17-OH形成分子内氢键将使活性降低.

A series of 16α-substituted estradiol derivatives were investigated by using ab initio (HF/STO-3G) method. A Quantitative Structure-Activity Relationship(QSAR) model of 16α-substituted derivatives was developed. The conclusions show as follows. (1)FMOs mainly locate in the center of the Relative Binding Affinity (RBA) for estradiol derivatives ring A, 3-OH and 17-OH, and the hydrogen bond between 16α-substituent and 17-OH will decreases the RBA, which support the view that 17-OH and 3-OH bind to the receptor with hydrogen bond. (2)The 16α-substitutents can cause steric hindrance which increase with the molecular volume, and decrease the RBAs of estradiol derivatives.