Stereoselective synthesis of (22R)- and (22S)-castasterone/ponasterone A hybrid compounds and evaluation of their molting hormone activity.
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.
Watanabe
Bunta
B
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, 6068502, Japan.
Nakagawa
Yoshiaki
Y
Ogura
Takehiko
T
Miyagawa
Hisashi
H
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D002777:Cholestanols / Q000138:chemical synthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004441:Ecdysterone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007301:Insect Hormones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008968:Molecular Conformation; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002777:Cholestanols; D007301:Insect Hormones; D011987:Receptors, Steroid; C034808:ecdysteroid receptor; D004441:Ecdysterone; C083545:castasterone; C008999:ponasterone A