title: Five new cassane diterpenes from Myrospermum frutescens with activity against Trypanosoma cruzi.
abstract: Five novel cassane diterpenes (1-5) with activity against Trypanosoma cruzi were isolated from leaves of Myrospermum frutescens. The structures were determined as 18-hydroxycassan-13,15-diene (1), 6beta,18-dihydroxycassan-13,15-diene (2), 6beta-hydroxy-18-acetoxycassan-13,15-diene (3), 18-acetoxy-13,15-diene-19-cassanoic acid (4), and 6beta,13beta-dihydroxy-18-acetoxycassan-14(17),15-diene (5). Structures were elucidated by spectroscopic analysis (NMR and HRCIMS) and by the synthesis of derivatives 2a and 2b. Compounds 3 and 5 were more active against the extracellular form of the parasite (11 and 16 microM, respectively) than the intracellular forms, while compounds 1 and 2 were more active against the more clinically relevant intracellular forms of the parasite (17 microM). Compounds 1 and 2 were approximately 9-fold more toxic toward T. cruzi than toward human fibroblasts, the cell type that serves as the parasite's mammalian host cell.
authors.affiliation: Laboratory of Natural Products, Faculty of Natural and Exact Sciences and Technology, Apartado 0824, University of Panama, Panama City, Republic of Panama.
authors.forename: Daniel Torres
authors.initials: DT
authors.lastname: Mendoza
authors.forename: Luis D
authors.initials: LD
authors.lastname: Ureña González
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ortega-Barría
authors.forename: Todd L
authors.initials: TL
authors.lastname: Capson
authors.forename: Luis Cubilla
authors.initials: LC
authors.lastname: Rios
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007887:Fabaceae / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010176:Panama; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D013237:Stereoisomerism; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D004224:Diterpenes; D014344:Trypanocidal Agents