摘要
本文研究了前列腺素合成酶抑制剂二苯丙烯腈类化合物(DPA)分子的空间结构和电子结构与其活性的关系,结果表明:丙烯腈基的前线亲电电荷密度越大、净负电荷越多、分子的电子平均能量越高,其抑制活性越高。双(P-甲氧基苯基)丙烯腈的活性很高(IC_(50)=2×10^(-9)M)与甲氧基的给电子能力有关。本文还提出受体与DPA结合部位的结构模型以及DPA的作用机理。
The molecular and electronic structures are studied based on the data of crystal structures and INDO calculation of quantum chemistry for several diphenylacrylonitrile (DPA) derivatives which have been found to be effective in inhibition of prostaglandin synthetase (PGSI). Our studies have led to formulation of a hypothetical model for the complementary receptor binding site. This model suggests the following binding points: (a) the electron-accepting group, which binds to the etheno or acrylonitrile group of the DPA molecule - an essential binding for receptor recognition, (b) a cationic center interacts with the cyano group, (c) hydrophobic binding to either phenyl ring, (d) the negatively charged group attracts the carbon atom that has a partial positive charge at the para position of either phenyl ring of the DPA molecule. The model rationalizes the structure-activity relationships and appears to be in agreement with reported biochemical studies of PGSI activity for DPA analogues.
