Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor
Musella, Simona di Sarno, Veronica Ciaglia, Tania Sala, Marina Spensiero, Antonia Scala, Maria Carmina Ostacolo, Carmine Andrei, Graciela Balzarini, Jan Snoeck, Robert Novellino, Ettore Campiglia, Pietro Bertamino, Alessia Gomez-Monterrey, Isabel M # ×
European Journal of Medicinal Chemistry vol:124 pages:773-781
We report the synthesis and antiviral activity of a new family of non-nucleoside antivirals, derived from the indole nucleus. Modifications of this template through Mannich and Friedel-Crafts reactions, coupled with nucleophilic displacement and reductive aminations led to 23 final derivatives, which were pharmacologically tested. Tryptamine derivative 17a was found to have a selective inhibitory activity against human varicella zoster virus (VZV) replication in vitro, being inactive against a variety of other DNA and RNA viruses. A structure-activity relationship (SAR) study showed that the presence of a biphenyl ethyl moiety and the acetylation at the amino group of tryptamine are a prerequisite for anti-VZV activity. The novel compound shows the same activity against thymidine kinase (TK)-competent (TK(+)) and TK-deficient (TK(-)) VZV strains, pointing to a novel mechanism of antiviral action.