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

Noélia Duarte, Nora Gyémánt, Pedro M. Abreu, Joseph Molnár, Maria José Umbelino Ferreira

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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-16α,17-dihydroxyatisan-3-one (4) and enf-16α,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 (1H-1H 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.

Original languageEnglish
Pages (from-to)162-168
Number of pages7
JournalPlanta Medica
Volume72
Issue number2
DOIs
Publication statusPublished - Feb 1 2006

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Keywords

  • Diterpenes
  • Euphorbia lagascae
  • Lathyrane
  • Multidrug resistance
  • P-glycoprotein
  • Phenolic compounds

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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