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
  • 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: [email protected].
  • 5. Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131, Napoli, Italy. Electronic address: [email protected].
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.