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

Disodium 3β,21-dihydroxypregn-5-en-20-one disulfate ( 2), sodium 3β,21-dihydroxypregn-5-en-20-one 3-sulfate ( 3), sodium 3β,21-dihydroxypregn-5-en-20-one 21-sulfate ( 4), and disodium 3β,6α-dihydroxy-5α-pregnan-20-one disulfate ( 6) have been synthesized and completely characterized for the first time from readily available materials. Sulfation was performed using triethylamine-sulfur trioxide complex in dimethylformamide as the sulfating agent. Selective sulfation of 3β,21-dihydroxypregn-5-en-20-one rendered sodium 3β,21-dihydroxypregn-5-en-20-one 3-sulfate ( 3) as the major compound. The synthetic sulfated steroids as well as natural disulfated polyhydroxysteroids ( 7–9) isolated by us from the antarctic ophiuroid Astrotoma agassizii and the synthetic derivatives disodium 2β,3α,21-trihydroxy-(20R)-cholesta-5,24-diene 3-acetate, 2,21-disulfate ( 7a) and 2β,3α,21-trihydroxy-(20R)-cholesta-5,24-diene ( 7b) were comparatively 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 groups at C-21 and C-2 or C-3 were the most effective in their inhibitory action against HSV-2 and also proved to be active against PV-3 and JV.