Antiviral Effect of Troger?s Base Derivatives against Herpesvirus Infection

PETRERA, ERINA; BRUTTOMESSO, ANDREA C.; TRUPP, LEANDRO; ALCHÉ, LAURA

Buenos Aires

Congreso; LXII Reunión anual de la Sociedad Argentina de Investigación Clínica; 2017

Sociedad Argentina de Investigación Clinica.

In one hand, the Herpes simplex virus (HSV), the prototype of double DNA strand viruses, have played a prominent role in the development of antivirals; in the other, Troger?s base (TB) structural features have been utilized in the design of DNA binders. This encouraged us to the study of the antiviral properties of this type of compounds.In this work we reported the synthesis and the antiviral effect of six novel TB derivatives against HSV infection.The key step in the synthesis was the skeleton construction, through the acid-catalyzed condensation between an aniline and paraformaldehyde. All final compounds were chromatographically purified and characterized by EM and 1D and 2D NMR techniques.Regarding the biological activity, it was found that the compounds were not cytotoxic in Vero cells, presenting CC50 values >300?ÝM. To evaluate the antiviral activity different concentration of the six TB derivatives were added after virus adsorption and 24 h later the supernatants were harvested and the viral titers were obtained by plaque assay. Most of the analyzed compounds inhibited virus yield of three strains of HSV-1 (HSV-1 KOS, and HSV-1 TK- strains B2006 and Field) and two strains of HSV-2 (HSV-2 G and HSV-2 MS). The compounds also modulated cytokine production in J774A1 macrophages cultures induced by bacterial LPS. The results obtained shown that these TB derivatives inhibit HSV in Vero cells and modulate cytokine production in macrophages.