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.
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;CAMPIGLIA, Pietro;BERTAMINO, Alessia;
2016-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.