title: Anti-herpetic and anti-dengue activity of abietane ferruginol analogues synthesized from (+)-dehydroabietylamine.
abstract: The abietane-type diterpenoid (+)-ferruginol (1), a bioactive compound isolated from several plants, has attracted much attention as consequence of its pharmacological properties, which includes antibacterial, antifungal, antimicrobial, cardioprotective, anti-oxidative, anti-plasmodial, leishmanicidal, anti-ulcerogenic, anti-inflammatory and antitumor actions. In this study, we report on the antiviral evaluation of ferruginol (1) and several analogues synthesized from commercial (+)-dehydroabietylamine. Thus, the activity against Human Herpesvirus type 1, Human Herpesvirus type 2 and Dengue Virus type 2, was studied. Two ferruginol analogues showed high antiviral selectivity index and reduced viral plaque-size in post-infection stages against both Herpes and Dengue viruses. A promising lead, compound 8, was ten-fold more potent (EC50 = 1.4 μM) than the control ribavirin against Dengue Virus type 2. Our findings suggest that the 12-hydroxyabieta-8,11,13-triene skeleton, which is characteristic of the diterpenoid ferruginol (1), is an interesting molecular scaffold for development of novel antivirals. In addition, the cytotoxic and antifungal activities of the synthesized ferruginol analogues have also been investigated. (©)20155 Elsevier Science. All rights reserved.
authors.affiliation: Group of Investigative Dermatology, Institute of Medical Research, Medicine Faculty, University of Antioquia, Medellin, A.A1226, Antioquia, Colombia; Translational and Molecular Medicine Group, Institute of Medical Research, Medicine Faculty, University of Antioquia, Medellin, Colombia.
authors.forename: Vicky C
authors.initials: VC
authors.lastname: Roa-Linares
authors.affiliation: Group of Investigative Dermatology, Institute of Medical Research, Medicine Faculty, University of Antioquia, Medellin, A.A1226, Antioquia, Colombia; Translational and Molecular Medicine Group, Institute of Medical Research, Medicine Faculty, University of Antioquia, Medellin, Colombia.
authors.forename: Yaneth M
authors.initials: YM
authors.lastname: Brand
authors.affiliation: Group of Investigative Dermatology, Institute of Medical Research, Medicine Faculty, University of Antioquia, Medellin, A.A1226, Antioquia, Colombia.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Agudelo-Gomez
authors.affiliation: Group of Investigative Dermatology, Institute of Medical Research, Medicine Faculty, University of Antioquia, Medellin, A.A1226, Antioquia, Colombia.
authors.forename: Verónica
authors.initials: V
authors.lastname: Tangarife-Castaño
authors.affiliation: Group of Investigative Dermatology, Institute of Medical Research, Medicine Faculty, University of Antioquia, Medellin, A.A1226, Antioquia, Colombia; Translational and Molecular Medicine Group, Institute of Medical Research, Medicine Faculty, University of Antioquia, Medellin, Colombia.
authors.forename: Liliana A
authors.initials: LA
authors.lastname: Betancur-Galvis
authors.affiliation: Translational and Molecular Medicine Group, Institute of Medical Research, Medicine Faculty, University of Antioquia, Medellin, Colombia.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Gallego-Gomez
authors.affiliation: Departamento de Química Orgánica, Universidad de Valencia, E-46100 Burjassot, Valencia, Spain. Electronic address: Miguel.A.Gonzalez@uv.es.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González
mesh_terms: D045784:Abietanes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003716:Dengue Virus / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D045784:Abietanes; D000998:Antiviral Agents; C431074:ferruginol; C000600819:dehydroabietylamine
keywords: Abietane; Antiviral; Dehydroabietylamine; Dengue; Diterpene; Ferruginol; Herpes