title: Structure-activity relationships for euphocharacins A-L, a new series of jatrophane diterpenes, as inhibitors of cancer cell P-glycoprotein.
abstract: The Mediterranean spurge Euphorbia characias L. afforded twelve new diterpenes based on a jatrophane skeleton named euphocharacins A-L. Their chemical structures were elucidated by extensive nuclear magnetic resonance and mass spectrometry methods. Euphocharacins A-L were tested as inhibitors of the daunomycin-efflux activity of P-glycoprotein from cancer cells. The results were used to extend the structure-activity relationship established for this class of compounds, highlighting the positive effects of propyl and benzoyl groups at positions 3 and 9, respectively, and evidencing the negative effect of a free hydroxyl group at position 2. Among the tested compounds, euphocharacins C and I showed an activity higher than cyclosporin to inhibit Pgp-mediated daunomycin transport.
authors.affiliation: Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli Federico II, Naples, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Corea
authors.forename: Ernesto
authors.initials: E
authors.lastname: Fattorusso
authors.forename: Virginia
authors.initials: V
authors.lastname: Lanzotti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Motti
authors.forename: Pierre-Noël
authors.initials: PN
authors.lastname: Simon
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.forename: Attilio
authors.initials: A
authors.lastname: Di Pietro
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D028481:Euphorbia; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D010936:Plant Extracts