title: Jatrophane diterpenes as P-glycoprotein inhibitors. First insights of structure-activity relationships and discovery of a new, powerful lead.
abstract: The Mediterranean spurge Euphorbia dendroides L. afforded a series of 10 closely related jatrophane polyesters, nine of which are new, which served as a base for the establishment of structure-activity relationships within this class of P-glycoprotein inhibitors. The results, while pointing to the general role of lipophilicity for activity, also highlighted the relevance of the substitution pattern at the positions 2, 3, and 5, suggesting the involvement of this fragment in binding. The most powerful compound of the series, euphodendroidin D (4), outperformed cyclosporin by a factor of 2 to inhibit Pgp-mediated daunomycin transport.
authors.affiliation: Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli Federico II, Via D. Montesano 49, I-80131 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: Orazio
authors.initials: O
authors.lastname: Taglialatela-Scafati
authors.forename: Giovanni
authors.initials: G
authors.lastname: Appendino
authors.forename: Mauro
authors.initials: M
authors.lastname: Ballero
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 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification*; D028481:Euphorbia / Q000737:chemistry*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004224:Diterpenes