A new P-glycoprotein inhibitor from the caper spurge (Euphorbia lathyris).
The macrocyclic lathyrane polyester Euphorbia factor L10 (1a) has been obtained from the seeds of the caper spurge (E. lathyris). The interaction of L10 (1a) and its acetyl derivative (1b) with P-glycoprotein, a multidrug transporter overexpressed in cancer cells and responsible for resistance to chemotherapy, was investigated. The results established lathyrane diterpenoids as a novel chemotype for P-glycoprotein inhibitors.
Appendino
Giovanni
G
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Viale Ferrucci 33, 28100 Novara, Italy. appendino@pharm.unipmn.it
Della Porta
Carla
C
Conseil
Gwenaëlle
G
Sterner
Olov
O
Mercalli
Enrico
E
Dumontet
Charles
C
Di Pietro
Attilio
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D028481:Euphorbia / Q000737:chemistry*; D005858:Germany; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D007938:Leukemia; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004224:Diterpenes; C474529:Euphorbia factor L10; C474530:Euphorbia factor L10, acetyl derivative