Discovery and biological evaluation of a new family of potent modulators of multidrug resistance: reversal of multidrug resistance of mouse lymphoma cells by new natural jatrophane diterpenoids isolated from Euphorbia species.
The effects of 15 jatrophane diterpene polyesters (1-3 and 5-16) isolated from lipophilic extracts of Euphorbia serrulata, E. esula, E. salicifolia, and E. peplus (Euphorbiaceae) on the reversion of multidrug resistance of mouse lymphoma cells were examined. The structures of five new compounds (1-5) were elucidated by spectroscopic methods, including HRFABMS, ESIMS, (1)H-(1)H homonuclear and (1)H-(13)C heteronuclear correlations, long-range correlation spectra, and NOESY experiments. The stereochemistry and absolute configuration of one compound (3) were determined by X-ray crystallography. The structure-activity relationship is discussed.
Hohmann
Judit
J
Department of Pharmacognosy, University of Szeged, H-6720 Szeged, Hungary. hohmann@pharma.szote.u-szeged.hu
Molnár
Joseph
J
Rédei
Dóra
D
Evanics
Ferenc
F
Forgo
Peter
P
Kálmán
Alajos
A
Argay
Gyula
G
Szabó
Pál
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000302:isolation & purification* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D028481:Euphorbia; D006814:Hungary; D008223:Lymphoma; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004224:Diterpenes