Evaluation of the antiviral activity of natural sulfated polyhydroxysteroids and their synthetic derivatives and analogs

Disodium 3 beta,21-dihydroxypregn-5-en-20-one disulfate (2), sodium 3 beta, 21-dihydroxypregn-5-en-20-one 3-sulfate (3), sodium 3 beta,21-dihydroxypreg n-5-en-20-one 21-sulfate (4), and disodium 3 beta,6 alpha-dihydroxy-5 alpha -pregnan-20-one disulfate (6) have been synthesized and completely characte rized for the first time from readily available materials. Sulfation was pe rformed using triethylamine-sulfur trioxide complex in dimethylformamide as the sulfating agent. Selective sulfation of 3 beta,21-dihydroxypregn-5-en- 20-one rendered sodium 3 beta,21-dihydroxypregn-5-en-20-one 3-sulfate (3) a s the major compound. The synthetic sulfated steroids as well as natural di sulfated polyhydroxysteroids (7-9) isolated by us from the antarctic ophiur oid Astrotoma agassizii and the synthetic derivatives disodium 2 beta,3 alp ha,21-trihydroxy-(20R)-cholesta-5,24-diene 3-acetate, 2,21-disulfate (7a) a nd 2 beta,3 alpha,21-trihydroxy-(20R)-cholesta-5,24-diene (7b) were compara tively evaluated for their inhibitory effect on the replication of one DNA (HSV-2) and two RNA (PV-3, JV) viruses. In general, steroids with sulfate g roups at C-21 and C-2 or C-3 were the most effective in their inhibitory ac tion against HSV-2 and also proved to be active against PV-3 and JV. (C) 19 99 Elsevier Science Inc. All rights reserved.