title: Antimalarial activity of abietane ferruginol analogues possessing a phthalimide group.
abstract: The abietane-type diterpenoid (+)-ferruginol, a bioactive compound isolated from New Zealand's Miro tree (Podocarpus ferruginea), displays relevant pharmacological properties, including antimicrobial, cardioprotective, anti-oxidative, anti-plasmodial, leishmanicidal, anti-ulcerogenic, anti-inflammatory and anticancer. Herein, we demonstrate that ferruginol (1) and some phthalimide containing analogues 2-12 have potential antimalarial activity. The compounds were evaluated against malaria strains 3D7 and K1, and cytotoxicity was measured against a mammalian cell line panel. A promising lead, compound 3, showed potent activity with an EC50 = 86 nM (3D7 strain), 201 nM (K1 strain) and low cytotoxicity in mammalian cells (SI>290). Some structure-activity relationships have been identified for the antimalarial activity in these abietane analogues.
authors.affiliation: Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Valencia, Spain. Electronic address: Miguel.A.Gonzalez@uv.es.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Clark
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Connelly
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: Fatima.rivas@stjude.org.
authors.forename: Fatima
authors.initials: F
authors.lastname: Rivas
mesh_terms: D045784:Abietanes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D056945:Hep G2 Cells; D006801:Humans; D010797:Phthalimides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology
chemical_list: D045784:Abietanes; D000962:Antimalarials; D010797:Phthalimides; D010936:Plant Extracts; C431074:ferruginol; C037431:phthalimide
keywords: Abietane; Antimalarial; Dehydroabietylamine; Diterpene; Ferruginol