title: Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor.
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.
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Musella
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: di Sarno
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Ciaglia
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Sala
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Spensiero
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Maria Carmina
authors.initials: MC
authors.lastname: Scala
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131, Napoli, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Ostacolo
authors.affiliation: Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.affiliation: Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131, Napoli, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy. Electronic address: abertamino@unisa.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertamino
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131, Napoli, Italy. Electronic address: imgomez@unina.it.
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Gomez-Monterrey
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015195:Drug Design; D014645:Herpesvirus 3, Human / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D007211:Indoles
keywords: Antiviral activity; Indole derivatives; TK-deficient strains; Varicella zoster virus