Watanabe Bunta, Nakagawa Yoshiaki, Ogura Takehiko, Miyagawa Hisashi
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, 6068502, Japan.
Steroids. 2004 Jul;69(7):483-93. doi: 10.1016/j.steroids.2004.04.005.
Two stereoisomers of a castasterone/ponasterone A hybrid compound, the (20R,22R) and (20R,22S)-isomers of 2alpha,3alpha,20,22-tetrahydroxy-5alpha-cholestan-6-one, were synthesized stereoselectively and their binding activity to the ecdysteroid receptor was determined. From the concentration-response curve for the inhibition of the incorporation of tritiated ponasterone A into ecdysteroid receptor containing insect cells, the concentration (IC50) required to inhibit 50% of the incorporation of radioactivity into cells was evaluated. The IC50 values of the (22R)- and (22S)-isomers were determined to be 0.30 and 38.9 microM against Kc cells, respectively, indicating that the (22R)-isomer is about 100 times more potent than the corresponding (22S)-isomer. IC50 values of these compounds against lepidopteran Sf-9 cells were determined to be 0.36 and 12.9 microM, respectively. The molting hormonal effect was examined in a Chilo suppressalis integument system and the 50% effective concentration for the stimulation of N-acetylglucosamine incorporation into the cultured integument was determined to be 2.7 microM for the (22R)-isomer, while the (22S)-isomer was inactive. On the other hand, both isomers did not show brassinolide-like activity in the rice lamina inclination assay.
合成了一种蜕皮甾酮/泼那甾酮A杂合化合物的两种立体异构体，即2α,3α,20,22 - 四羟基 - 5α - 胆甾烷 - 6 - 酮的(20R,22R)和(20R,22S)异构体，并测定了它们与蜕皮甾酮受体的结合活性。根据抑制氚标记的泼那甾酮A掺入含蜕皮甾酮受体的昆虫细胞的浓度 - 反应曲线，评估了抑制50%放射性掺入细胞所需的浓度(IC50)。(22R) - 和(22S) - 异构体对Kc细胞的IC50值分别测定为0.30和38.9微摩尔，表明(22R) - 异构体的效力比相应的(22S) - 异构体高约100倍。这些化合物对鳞翅目Sf - 9细胞的IC50值分别测定为0.36和12.9微摩尔。在二化螟体表系统中检测了蜕皮激素效应，对于(22R) - 异构体，刺激N - 乙酰葡糖胺掺入培养体表的50%有效浓度测定为2.7微摩尔，而(22S) - 异构体无活性。另一方面，在水稻叶片倾斜试验中，两种异构体均未表现出油菜素内酯样活性。
