Apoptosis induction and modulation of P-glycoprotein mediated multidrug resistance by new macrocyclic lathyrane-type diterpenoids

Noélia Duarte, Andras Varga, Georg Cherepnev, Rita Radics, J. Molnár, Maria José U Ferreira

Research output: Contribution to journalArticle

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Abstract

The macrocyclic lathyrane diterpenes, latilagascenes D-F (1-3) and jolkinol B (4), were isolated from the methanol extract of Euphorbia lagascae, and evaluated for multidrug resistance reversing activity on mouse lymphoma cells. All compounds displayed very strong activity compared with that of the positive control, verapamil. The structure-activity relationship is discussed. The evaluation of compounds 1 and 4, and of latigascenes A-C (5-7), isolated from the same species, as apoptosis-inducers was also carried out. Compound 1 was the most active. Furthermore, in the model of combination chemotherapy, the interaction between the doxorubicine and latilagascene B (6) was studied in vitro, on human MDR1 gene transfected mouse lymphoma cells, showing that the type of interaction was synergistic. Latilagascenes D-F (1-3) are new compounds whose structures were established on the basis of spectroscopic methods, including 2D NMR experiments (COSY, HMQC, HMBC and NOESY).

Original languageEnglish
Pages (from-to)546-554
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 1 2007

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Diterpenes
Multiple Drug Resistance
P-Glycoprotein
Lymphoma
Modulation
Apoptosis
Euphorbia
Chemotherapy
Structure-Activity Relationship
Verapamil
Combination Drug Therapy
Cell Communication
Methanol
Genes
Nuclear magnetic resonance
Experiments
lathyrane
latilagascene F
latilagascene D
jolkinol B

Keywords

  • Antiproliferative
  • Apoptosis
  • Euphorbia lagascae
  • Macrocyclic lathyrane diterpenes
  • Multidrug resistance
  • P-glycoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Apoptosis induction and modulation of P-glycoprotein mediated multidrug resistance by new macrocyclic lathyrane-type diterpenoids. / Duarte, Noélia; Varga, Andras; Cherepnev, Georg; Radics, Rita; Molnár, J.; Ferreira, Maria José U.

In: Bioorganic and Medicinal Chemistry, Vol. 15, No. 1, 01.01.2007, p. 546-554.

Research output: Contribution to journalArticle

Duarte, Noélia ; Varga, Andras ; Cherepnev, Georg ; Radics, Rita ; Molnár, J. ; Ferreira, Maria José U. / Apoptosis induction and modulation of P-glycoprotein mediated multidrug resistance by new macrocyclic lathyrane-type diterpenoids. In: Bioorganic and Medicinal Chemistry. 2007 ; Vol. 15, No. 1. pp. 546-554.
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