2. Academic Validation
  3. Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor

Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor

  • Eur J Med Chem. 2016 Nov 29:124:773-781. doi: 10.1016/j.ejmech.2016.09.014.
Simona Musella 1,  Veronica di Sarno 1,  Tania Ciaglia 1,  Marina Sala 1,  Antonia Spensiero 1,  Maria Carmina Scala 1,  Carmine Ostacolo 2,  Graciela Andrei 3,  Jan Balzarini 3,  Robert Snoeck 3,  Ettore Novellino 2,  Pietro Campiglia 1,  Alessia Bertamino 4,  Isabel M Gomez-Monterrey 5
Affiliations

Affiliations

  • 1 Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
  • 2 Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131, Napoli, Italy.
  • 3 Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium.
  • 4 Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy. Electronic address: abertamino@unisa.it.
  • 5 Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131, Napoli, Italy. Electronic address: imgomez@unina.it.
PMID: 27639368 DOI: 10.1016/j.ejmech.2016.09.014
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.

Keywords

Antiviral activity; Indole derivatives; TK-deficient strains; Varicella zoster virus.

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