title: Jatrophane diterpenes from Euphorbia mellifera and their activity as P-glycoprotein modulators on multidrug-resistant mouse lymphoma and human colon adenocarcinoma cells.
abstract: Three new macrocyclic jatrophane diterpenes, named euphomelliferine (1) and euphomelliferenes A (2) and B (3), and one new tetracyclic triterpene, 19(10→9)-abeo-8α,9β,10α-tirucalla-5,25-diene-3β,24-diol (6, C-24 epimers), were isolated from the methanolic extract of Euphorbia mellifera. A known ingenane (7) and two jatrophane diterpenes (4 and 5) were also isolated. Their structures were elucidated by extensive spectroscopic methods, including 1D and 2D homo- and heteronuclear NMR experiments. Jatrophane diterpenes 1-3 and 5 were evaluated for their effects on the reversion of multidrug resistance (MDR) mediated by P-glycoprotein, by using the rhodamine-123 exclusion test, on human MDR1 gene-transfected mouse lymphoma cells (L5178Y MDR) and on human colon adenocarcinoma cells (COLO 320). The apoptosis-inducing activity of these compounds was also tested on COLO 320 cells, using the annexin-V/propidium iodide assay. Diterpenes 1 and 2 displayed significant MDR reversing activity, in a dose-dependent manner, on both cancer cell models. The tested compounds did not induce apoptosis in the COLO 320 cells.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon , Avenida Prof. Gama Pinto 1649-003, Lisbon, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Valente
authors.forename: Mariana
authors.initials: M
authors.lastname: Reis
authors.forename: Noélia
authors.initials: N
authors.lastname: Duarte
authors.forename: Julianna
authors.initials: J
authors.lastname: Serly
authors.forename: Joséph
authors.initials: J
authors.lastname: Molnár
authors.forename: Maria-José U
authors.initials: MJ
authors.lastname: Ferreira
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000494:pharmacology*; D000465:Algorithms; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011174:Portugal; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C587534:19(10-9)-abeo-8alpha,9beta,10alpha-tirucalla-5,25-diene-3beta,24-diol; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004224:Diterpenes; D014315:Triterpenes; C587532:euphomelliferene A; C587533:euphomelliferene B; C587531:euphomelliferine; C530110:ingenane; C530345:jatrophane