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Abstract:

Brassinosteroids are a novel group of steroids that appear to be ubiquitous in plants and are essential for normal plant growth and development. It has been previously reported that brassinosteroid analogues exert an antiviral activity against herpes simplex virus type 1 (HSV-1) and arenaviruses. In the present study, we report the chemical synthesis of compounds (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (2), (22S,23S)-5α-fluoro-3β-22,23-trihydroxystigmastan-6-one (3), (22S,23S)-3β,5α,22,23-tetrahydroxy-stigmastan-6-one (4) as well as their antiherpetic activity both in a human conjunctive cell line (IOBA-NHC) and in the murine herpetic stromal keratitis (HSK) experimental model. All compounds prevented HSV-1 multiplication in NHC cells in a dose dependent manner when added after infection with no cytotoxicity. Administration of compounds 2, 3, and 4 to the eyes of mice at 1, 2, and 3 days post-infection delayed and reduced the incidence of HSK, consisting mainly of inflammation, vascularization, and necrosis, compared to untreated, infected mice. However, viral titers of eye washes showed no differences among samples from treated and untreated mice. Since the decrease in the percentage of mice with ocular lesions occurred 5 days after treatment had ended, we suggest that brassinosteroids 2, 3, and 4 did not exert a direct antiviral effect in vivo, but rather may play a role in immune-mediated stromal inflammation, which would explain the improvement of the clinical signs of HSK observed. © 2004 Elsevier Inc. All rights reserved.

Registro:

Documento: Artículo
Título:In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues
Autor:Michelini, F.M.; Ramírez, J.A.; Berra, A.; Galagovsky, L.R.; Alché, L.E.
Filiación:Laboratorio de Virología, Depto. de Quím. Biol., Fac. Cie. Exact. Y Nat.-UBA, Cd. U., Argentina
Depto. de Quím. Orgán., Fac. de Ciencias Exactas Y Naturales, Cd. Univ., Pabellon II, 1428 B., Argentina
Lab. de Inmunopatologia Ocular, Fac. de Med. Univ. de Buenos Aires, J.E. Uriburu 950, E.P., 1113 B., Argentina
Palabras clave:Antiviral activity; Brassinosteroids; HSV-1; Human conjunctive cell line; Murine herpetic stromal keratitis; Steroid; 3beta bromo 5alpha 22,23 trihydroxystigmastan 6 one; 3beta,5alpha,22,23 tetrahydroxystigmastan 6 one; 5alpha fluoro 3beta 22,23 trihydroxystigmastan 6 one; antivirus agent; brassinosteroid; steroid; unclassified drug; animal cell; antiviral activity; article; cell division; cell line; comparative study; cytotoxicity; dose response; drug synthesis; eye injury; Herpes simplex virus 1; human; human cell; immune mediated injury; in vitro study; in vivo study; inflammation; male; morbidity; mouse; necrosis; nonhuman; sample; stomatitis; vascularization; virus infection; Animals; Anti-Inflammatory Agents; Antiviral Agents; beta-Galactosidase; Cell Line; Cell Survival; Cercopithecus aethiops; Cholestanones; Dose-Response Relationship, Drug; Herpesvirus 1, Human; Humans; Inflammation; Male; Mice; Mice, Inbred BALB C; Models, Chemical; Spectrophotometry; Steroids; Stigmasterol; Time Factors; Vero Cells; Herpes; Human herpesvirus 1; Murinae
Año:2004
Volumen:69
Número:11-12
Página de inicio:713
Página de fin:720
DOI: http://dx.doi.org/10.1016/j.steroids.2004.04.011
Título revista:Steroids
Título revista abreviado:Steroids
ISSN:0039128X
CODEN:STEDA
CAS:(22S,23S)-3beta-bromo-5alpha,22,23-trihydroxystigmastan-6-one; 3,5,22,23-tetrahydroxystigmastan-6-one; Anti-Inflammatory Agents; Antiviral Agents; Cholestanones; Steroids; Stigmasterol, 83-48-7; beta-Galactosidase, 3.2.1.23
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0039128X_v69_n11-12_p713_Michelini

Referencias:

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Citas:

---------- APA ----------
Michelini, F.M., Ramírez, J.A., Berra, A., Galagovsky, L.R. & Alché, L.E. (2004) . In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues. Steroids, 69(11-12), 713-720.
http://dx.doi.org/10.1016/j.steroids.2004.04.011
---------- CHICAGO ----------
Michelini, F.M., Ramírez, J.A., Berra, A., Galagovsky, L.R., Alché, L.E. "In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues" . Steroids 69, no. 11-12 (2004) : 713-720.
http://dx.doi.org/10.1016/j.steroids.2004.04.011
---------- MLA ----------
Michelini, F.M., Ramírez, J.A., Berra, A., Galagovsky, L.R., Alché, L.E. "In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues" . Steroids, vol. 69, no. 11-12, 2004, pp. 713-720.
http://dx.doi.org/10.1016/j.steroids.2004.04.011
---------- VANCOUVER ----------
Michelini, F.M., Ramírez, J.A., Berra, A., Galagovsky, L.R., Alché, L.E. In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues. Steroids. 2004;69(11-12):713-720.
http://dx.doi.org/10.1016/j.steroids.2004.04.011