Synthesis and antiviral activity of sulfated and acetylated derivatives of 2beta,3alpha-dihydroxy-5alpha-cholestane.
Five new steroid sulfates, sodium 2beta,3alpha-dihydroxy-5alpha-cholestane 3-sulfate (6), sodium 2beta,3alpha-dihydroxy-5alpha-cholestane 2-sulfate (7), disodium 2beta,3alpha-dihydroxy-5alpha-cholestane disulfate (8), sodium 3alpha-acetoxy-2beta-hydroxy-5alpha-cholestane 2-sulfate (12), and sodium 2beta-acetoxy-3alpha-hydroxy-5alpha-cholestane 3-sulfate (13), have been synthesized starting from 3beta-hydroxy-5alpha-cholestane (1). The synthetic steroids were completely characterized by one-dimensional and two-dimensional NMR and FABMS spectra. Sulfation was performed using triethylamine-sulfur trioxide complex in dimethylformamide as the sulfating agent. The sulfated steroids were comparatively evaluated for their inhibitory effect on the replication of herpes simplex virus type 2 (HSV-2). Compounds 7 and 8 were the most effective in their inhibitory action against HSV-2. The disulfated steroid 8 also proved to be active against DEN-2 and JV.
Santos
Gustavo A Garrido
GA
Departamento de Qui;mica Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Argentina.
Murray
Ana P
AP
Pujol
Carlos A
CA
Damonte
Elsa B
EB
Maier
Marta S
MS
D000107:Acetylation; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D002522:Chlorocebus aethiops; D002777:Cholestanols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D018258:Herpesvirus 2, Human / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013431:Sulfates / Q000737:chemistry*; D014709:Vero Cells
C478778:2,3-dihydroxycholestane; D000998:Antiviral Agents; D002777:Cholestanols; D013431:Sulfates