Studies on the mechanism of estrogen biosynthesis. 8. The development of inhibitors of the enzyme system in human placenta.
Studies on the mechanism of estrogen biosynthesis. 8. The development of inhibitors of the enzyme system in human placenta.
复制标题
雌激素生物合成机制的研究。
作者：
W. C. Schwarzel;William G. Kruggel;H. J. Brodie
系统评价了100多种甾体和一些非甾体类化合物作为人胎盘微粒体雌激素生物合成抑制剂的结构特征。将微粒体与潜在抑制剂一起或不与潜在抑制剂一起预孵育，然后与[4- 14 C]雄甾-4-烯-3，17-二酮或[4- 14 C] 3 β-羟基雄甾- S-en-17-酮（DHA）和NADPH生成系统一起孵育。在添加氚化雌激素作为回收标记物后，通过薄层色谱法分离雌激素，并使用双标记闪烁计数法测定，以确定转化百分比和产生的抑制。C_（10）A_（4 -3-）酮化合物比相应的A环还原的（5x或5 p）化合物或A_（4 -3-）酮19-去甲化合物是更好的抑制剂。与Δ 4 -3-酮系统的进一步缀合也是有益的，使得Δ 1，4 ′ 6 -3-酮、Δ 4 -6-3-酮和Δ 4 - 3，6-二酮化合物是有效的。在所有情况下，17-酮基在提供抑制特性方面上级17 P-羟基基团，而17 P-乙酸酯和甲酸酯基团...
Structural features of over 100 steroids and some non—steroids were evaluated systematically as inhibitors of estrogen biosynthesis in human placental microsomes. The microsomes were preincubated with and without potential inhibitors, and then were incubated with [4–14C] androst–4–ene–3,17–dione or [4–14C]3P—hydroxyandrost— S—en—17–one (DHA) and an NADPH generating system. After adding tritiated estrogens as recovery markers, the estrogens were isolated by thin—layer chromatography and were assayed using dual—label scintillation counting to determine percent conversion and inhibition produced. C10 A4–3–keto compounds were better inhibitors than the corresponding ring A reduced (5<x or 5P) compounds or A4–3–keto 19–nor compounds. Further conjugation with the A4—3–keto system was also beneficial so that A1.4'6–3–one, A4–6–3–one and A4– 3,6–dione compounds were effective. The 17–keto was superior to the 17P—hydroxy group in providing inhibitory properties in all cases, while the 17P—acetate and formate group...