Evaluation of the antiviral activity of natural sulfated polyhydroxysteroids and their synthetic derivatives and analogs.
Disodium 3beta,21-dihydroxypregn-5-en-20-one disulfate (2), sodium 3beta,21-dihydroxypregn-5-en-20-one 3-sulfate (3), sodium 3beta,21-dihydroxypregn-5-en-20-one 21-sulfate (4), and disodium 3beta,6alpha-dihydroxy-5alpha-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 3beta,21-dihydroxypregn-5-en-20-one rendered sodium 3beta,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 2beta,3alpha,21-trihydroxy-(20R)-cholesta-5,24-diene 3-acetate, 2,21-disulfate (7a) and 2beta,3alpha,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.
Comin
M J
MJ
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Maier
M S
MS
Roccatagliata
A J
AJ
Pujol
C A
CA
Damonte
E B
EB
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004447:Echinodermata / Q000737:chemistry; D018258:Herpesvirus 2, Human / Q000187:drug effects; D018051:Junin virus / Q000187:drug effects; D017955:Poliovirus / Q000187:drug effects; D013431:Sulfates / Q000737:chemistry*; D014709:Vero Cells / Q000187:drug effects
C121073:2,3,21-trihydroxycholesta-5,24-diene 2,21-disulfate; C121071:2,3,21-trihydroxycholesta-5,24-diene 3-acetate 2,21-disulfate; C121072:2,3,21-trihydroxycholesta-5-ene 2,21-disulfate; D000998:Antiviral Agents; D013431:Sulfates; D002784:Cholesterol