The biological activities of diethylstilbestrol and its derivatives.

Abstract

Diethylstilbestol (I), a nonsteroidal estrogen, showed strong coronary vasodilator action on isolated guinea-pig heart, as well as ichthyotoxicity and antimicrobial activity. First, the coronary vasodilator action of I (ED50 : 0.26μg/heart) on isolated guinea-pig heart was much stronger than that of papaverine (ED50 : 7.0μg/heart) used as a standard. On the other hand, the activities of derivatives of I, i. e., I-diphosphate (II), I-dimethyl ether (III), I-diacetate (IV), I-dipropionate (V) and hexestrol (VI) were weaker than that of I. Second, I showed strong ichthyotoxicity (median tolerance limit at 48h : 3.30 ppm in Oryzias latipes and 4.50 ppm in Carassius auratus). On the other hand, the ichthyotoxic activities of II-V were weaker than that of I. However, VI showed the same toxicity as I on both fishes. Third, the antimicrobial activities of II-V were weaker than that of I, whereas that of VI was stronger. In particular, I and VI showed strong antifungal activity against Trichophyton spp. It was concluded that both the hydroxyl groups attached to the benzene rings and the transolefin structure are necessary for coronary vasodilator action, while only the hydroxyl groups attached to the benzene ring are necessary for the ichthyotoxic and antimicrobial activities.