Inhibition of human placental aromatase by novel homologated 19-oxiranyl and 19-thiiranyl steroids.
Inhibition of human placental aromatase by novel homologated 19-oxiranyl and 19-thiiranyl steroids.
复制标题
新型同源 19-oxiranyl 和 19-thiiranyl 类固醇抑制人胎盘芳香酶。
DOI：
10.1021/jm00108a016
复制
发表时间：
1991
影响因子：
7.3
通讯作者：
Robinson,CH
中科院分区：
文献类型：
--
作者：
Childers,WE;Silverton,JV;KellisJr,JT;Vickery,LE;Robinson,CH
合成了19-环氧乙烷基雄甾-4-烯-3，17-二酮（8a，B）和9-硫杂环丙烷基雄甾-4-烯-3，17-二酮（9a，B）。通过X-射线晶体学分析确定了化合物8a的构型和构象。所有四种化合物都被证明是人胎盘芳香化酶的竞争性抑制剂。在每个系列中，硫杂环丙烷比相应的环氧乙烷具有更强的抑制作用，2 ′ S异构体（8b和9 b）比2 ′ R（8a和9a）非对映异构体具有更好的抑制作用。用纯化的人胎盘芳香化酶进行的光谱研究表明，2'S化合物8b和9 b的环氧乙烷基氧和硫杂环丙烷基硫与酶的血红素铁配位。
Novel homologated 19-oxiranyl-and 9-thiiranylandrost-4-ene-3, 17-diones (8a, b and 9a, b, respectively) have been synthesized.. The configuration and conformation of compound 8a have been establishedby X-ray crystallographic analysis. All four compounds have been shown to be competitiveinhibitors of human placental aromatase. The thiiranes were more potent inhibitors than the correspondingoxiranes, and the 2'S isomers (8b and 9b) were better inhibitors than the2'R (8a and 9a) diastereomers in each series. Spectroscopic studies with purified human placental aromatase suggest that the oxiranyl oxygen and thiiranyl sulfur of 2'S compounds 8b and 9b coordinate to the enzyme’s heme iron.