Actividad biológica de esteroides de síntesis química frente a infecciones causadas por virus de importancia en la salud humana

More than 90% of all human diseases are caused by viral infections for most of which no prophylactic vaccines exist. There are no specific antivirals for Adenoviruses (AdV), which produce acute respiratory infections and keratoconjunctivitis, among others, and ribavirin is used only in specific clin...

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Autor principal: Gallardo, María José
Otros Autores: Michelini, Flavia Mariana
Formato: Tesis de maestría acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2017
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AdV
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1545
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1545.dir/1545.PDF
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Sumario:More than 90% of all human diseases are caused by viral infections for most of which no prophylactic vaccines exist. There are no specific antivirals for Adenoviruses (AdV), which produce acute respiratory infections and keratoconjunctivitis, among others, and ribavirin is used only in specific clinical situations. Another virus of clinical importance is Herpes simplex type 1 (HSV-1), which causes oral-facial infections, stromal keratitis and encephalitis. Although the treatment of choice against HSV-1 is acyclovir, it presents the therapeutic limitation of the appearance of mutant strains resistant to this antiviral. Azasteroids are steroid analogues for which interesting biological properties have been described, such as anticancer, antifungal and antibacterial. Some azasteroid analogs evaluated in our laboratory have broad spectrum antiviral activity. The aim of this work is to evaluate the antiviral activity of new azasteroids against AdV and HSV-1, to investigate the stage of the viral multiplication cycle in which the active compounds act and to analyze their immunomodulatory/anti-inflammatory activity.\nU-20 series azasteroids showed antiviral activity against AdV and HSV-1. Such inhibitory activity is not due to a virucidal action. The compounds do not affect the adsorption or internalization of the viral particles, but they would be inhibiting early and late stages of viral multiplication, including protein synthesis. Also, compound U20-1 is able to modulate the secretion of pro-inflammatory cytokines.\nIn conclusion, the synthetic azasteroids analyzed have a dual activity as antivirals and immunomodulators, which make them ideal candidates for treating immunopathologies of viral origin such as adenoviral keratoconjunctivitis and herpetic stromal keratitis.