Sterol analogues with diamide side chains interfere with the intracellular localization of viral glycoproteins

The need to develop novel antiviral agents encouraged us to assess the antiviral activity of synthetic sterol analogues with a diamide side chains. Cytotoxicity and antiviral activity of a family of azasterol previously synthesized was evaluated against herpes simplex virus 1 (HSV-1) (KOS and B2006) and vesicular stomatitis virus (VSV). This family of compounds was extended by the synthesis of novel analogs using an Ugi multicomponent reaction and their ability to inhibit viral multiplication was also evaluated. The results show that some of the compounds tested exert an antiviral activity. Besides, the effect of the azasterols on the intracellular localization of viral glycoproteins was examined. Strikingly, alteration on the glycoprotein D (gD) of HSV-1 fluorescence pattern was observed with both the antiherpetic compounds and the inactive azasterols.

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► Sterol analogues with diamide side chains were synthesized by Ugi reaction.
► All compounds were tested for their in vitro antiviral and cytotoxic activity.
► Antiherpetic and inactive azasterols altered the localization of viral glycoproteins.