New macrocyclic lathyrane diterpenes, from Euphorbia lagascae, as inhibitors of multidrug resistance of tumour cells.

Abstract

The new macrocyclic lathyrane diterpenes latilagascenes A and B ( 1 and 2), the diacetylated derivative of 2, latilagascene C ( 3), and the known diterpenes ent-16alpha,17-dihydroxyatisan-3-one ( 4) and ent-16alpha,17-dihydroxykauran-3-one ( 5), isolated from the methanol extract of Euphorbia lagascae, were examined for their effects on the reversal of multidrug resistance (MDR) on mouse lymphoma cells. Among the active lathyrane derivatives 1 - 3, compound 2 displayed the highest inhibition of rhodamine 123 efflux of human MDR1 gene transfected mouse lymphoma cells when compared to the untreated cells or the positive control verapamil. The new compounds are the first macrocyclic lathyrane diterpenes showing oxidation at C-16, whose structures were characterized by extensive spectroscopic methods, including 2D NMR experiments ( (1)H- (1)H COSY, HMQC, HMBC and NOESY). The known phenolic compounds vanillic acid ( 6), p-salicylic acid ( 7), isofraxidin ( 8) and cleomiscosin A ( 9) were also isolated from this species.

• Authors: Noélia Duarte, Nora Gyémánt, Pedro M Abreu, Joseph Molnár, Maria-José U Ferreira
• Journal: Planta medica (Planta Med) Vol. 72 Issue 2 Pg. 162-8 (Feb 2006) ISSN: 0032-0943 [Print] Germany
• PMID: 16491453 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Diterpenes
• Plant Extracts

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Diterpenes (chemistry, isolation & purification, pharmacology)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Euphorbia (chemistry)
• Genes, MDR
• Humans
• Lymphoma (metabolism)
• Mice
• Nuclear Magnetic Resonance, Biomolecular
• Plant Extracts (chemistry, pharmacology)
• Transfection