Uterotropic and anti-implantation activities of certain resorcylic acid lactone derivatives.

Abstract

This article discusses the oral estrogenic activity of zearalane a resorcyclic acid lactone (RAL) derivative produced by the fungus Gibberella zeae and its derivatives. The criteria used to determine such activity were uterine weight increase in immature rats and antifertility potency in mature rats. Zearalane (I) and its analogues Compound II 7-formal zearalane and Compound III 7-carboxy zearalane were used. Uterotropic assays were conducted using 21 day old female Carworth rats. 6 rats were used for each dose level. The doses were given by gavage in .2 ml sesame oil daily for 3 days. The uterotropic response was measured against the reference compound diethylstilbesterol(DES). In the determination of antifertility activity adult virgin female Holtzman rats were mated and vaginal smears were checked daily for sperm. The day sperm was detected was day 1 of pregnancy. One day 2 of pregnancy when rats were particularly suceptive to action of estrogens test compounds were administered in .2 ml of sesame oil as a single oral dose. Animals were autopsied on day 9 and the number of implantation recorded. The effective dose was the smallest amount of compound necessary to inhibit implantation completely in all animals. Additions of the 7-position enhanced the estrogenic and anti-implantation activities of zearalane. The more active isomer of 7-carboxy zearalane proved to be at least 100 times as estrogenic as zearalane and one tenth as active as DES. Anti-implantation potency was increased in a corresponding manner. There was no unequivocal seperation of estrogenic and anti-implantation activities noted in any of the compounds tested.