STRUCTURE-FUNCTION RELATIONSHIP STUDY OF YUEHCHUKENE .1. ANTI-IMPLANTATION AND ESTROGENIC ACTIVITIES OF SUBSTITUTED YUEHCHUKENE DERIVATIVES

(+/-)-Yuehchukene (YCK) is a novel bis-indole alkaloid with potent anti-implantation activity in rats. The present paper reports the activity of YCK derivatives by substitution on the parent compound. Substitutions on the indole nitrogens or on 2- and 5'- positions of the indole moiety abolished activity. N-1'-methylation of the free indole only permitted a 30% residual activity. Saturation of the C-9-C-10 cyclohexenyl double bond did not affect activity at all. Hydroxylation, whether on the C-9-C-10 double bond, or at C2 or C5, rendered the hydroxylated derivatives inactive. This suggests that the active metabolite in anti-implantation was probably not a hydroxylated derivative carrying estrogenic activity.