Anti-herpetic and anti-inflammatory activities of two new synthetic 22,23-dihydroxylated stigmastane derivatives.
Stromal keratitis resulting from ocular infection with Herpes simplex virus type 1 (HSV-1) is a common cause of blindness. This report investigates the antiviral and anti-inflammatory properties of two new synthetic stigmastane analogs in the experimental model of HSV-1-induced ocular disease in mice. (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (1) and (22S,23S)-22,23-dihydroxystigmasta-1,4-dien-3-one (2) exhibited anti-HSV-1 activity in vitro and ameliorated the signs of murine herpetic stromal keratitis (HSK), although none of the compounds showed antiviral activity in vivo. We discuss that the improvement of HSK could be due to an immunomodulatory effect of both compounds.
Michelini
Flavia M
FM
Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina.
Ramírez
Javier A
JA
Berra
Alejandro
A
Galagovsky
Lydia R
LR
Alché
Laura E
LE
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism; D005562:Formazans / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D016849:Keratitis, Herpetic / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D013053:Spectrophotometry; D013265:Stigmasterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors; D014709:Vero Cells; D001616:beta-Galactosidase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D005562:Formazans; D013778:Tetrazolium Salts; C079782:MTT formazan; D013265:Stigmasterol; D001616:beta-Galactosidase