Embryotoxicity of 9-(S)-(2,3-dihydroxypropyl)adenine

Embryotoxic properties of a novel nucleoside analog, 9-(S)-(2,3-dihydroxypropyl)adenine (DHPA), with powerful antiviral activity were estimated using the Chick Embryotoxicity Screening Test (CHEST). Exerting no substantial influence upon function of the caudal morphogenetic system on Day 1.5 (stages HH 10-11), the substance manifested strong embryotoxic action when administered in 30- and 100 microgram doses on Days 2 or 3. Deviant morphogenesis involved brain vesicles eyes, the face, body wall, extremities, the heart, and great vessels. The malformations often combined into the characteristic triad comprising microphthalmia, cleft beak, and reduction deformities of the limbs. Embryotoxic properties of an enantiomer (R)-DHPA were less frequently expressed, when compared with those of (S)-DHPA, parallelling their known antiviral activity. The effects of DHPA can be substantially reduced by simultaneous administration of adenine nucleosides. The distribution analysis of (S)-DHPA after application on Day 3 revealed most of the drug unchanged in the yolk and the embryo proper indicating that for expression of the embryotoxic properties no metabolic activation of DHPA was needed. As the embryotoxicity of DHPA was confirmed, even in mice, the biological effect of the drug seems to be of a general character.