New sterol analogues with antiviral activity

MARÍA E DÁVOLA; LAURA E. ALCHÉ; JAVIER A. RAMIREZ; ANDREA BARQUERO

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2011

The threat of emerging viruses and the appearance of viral strains resistant to therapeutic agents lead to the continuous search for innovative antiviral compounds. Steroids are an attractive source for antiviral drug discovery since these compounds are known to possess several biological properties. Previously, we have reported a new synthetic procedure to obtain sterol analogues based on an Ugi four-component reaction. This approach was successfully applied to obtain a family of eight azasterols with a polyfunctionalized side chain at C-16. The new azasterols were evaluated for their cytotoxicity and activity towards HSV-1 and VSV in Vero cells. Furthermore, we examined the effect of the compounds on the transport of HSV-1 glycoproteins by immunofluorescence staining. The antiviral assay revealed that all tested compounds have antiviral effect against HSV-1 at subtoxic concentrations. However, no activity against VSV was observed for any of them. Moreover, the active compounds would be affecting the viral glycoproteins transport since accumulation of gD fluorescence at juxtanuclear sites was visualized. In conclusion, these sterol analogues were identified as novel anti-HSV-1 agents. Further studies are under way to decipher the detailed antiviral mechanism of action of these compounds.