New potent P-glycoprotein modulators with the cucurbitane scaffold and their synergistic interaction with doxorubicin on resistant cancer cells

Cátia Ramalhete, J. Molnár, Silva Mulhovo, Virgílio E. Rosário, Maria José U Ferreira

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The novel cucurbitacins, balsaminagenin A and B (1-2) and balsaminoside A (3) and the know cucurbitacin karavelagenin C (4), together with five new mono or diacylated derivatives (5-9) of karavelagenin C were evaluated for multidrug resistance reversing activity on human MDR1 gene transfected mouse lymphoma cells. Compounds 2-6 exhibited a strong activity compared with that of the positive control, verapamil. Structure-activity relationships are discussed. Moreover, in the checkerboard model of combination chemotherapy, the interaction between doxorubicin and compounds 2-5 synergistically enhanced the effect of the anticancer drug. Compounds 1-4 were isolated from the aerial parts of Momordica balsamina L. The structures of the compounds were established on the basis of spectroscopic methods including 2D NMR experiments (COSY, HMQC, HMBC and NOESY).

Original languageEnglish
Pages (from-to)6942-6951
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number19
DOIs
Publication statusPublished - Oct 1 2009

Fingerprint

Momordica
Cucurbitacins
Chemotherapy
Multiple Drug Resistance
P-Glycoprotein
Structure-Activity Relationship
Verapamil
Combination Drug Therapy
Human Activities
Scaffolds
Doxorubicin
Modulators
Lymphoma
Genes
Cells
Nuclear magnetic resonance
Antennas
Derivatives
Pharmaceutical Preparations
Neoplasms

Keywords

  • Cucurbitane-type triterpenes
  • Momordica balsamina
  • Multidrug resistance
  • P-glycoprotein MDR modulators
  • Synergism

ASJC Scopus subject areas

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

Cite this

New potent P-glycoprotein modulators with the cucurbitane scaffold and their synergistic interaction with doxorubicin on resistant cancer cells. / Ramalhete, Cátia; Molnár, J.; Mulhovo, Silva; Rosário, Virgílio E.; Ferreira, Maria José U.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 19, 01.10.2009, p. 6942-6951.

Research output: Contribution to journalArticle

Ramalhete, Cátia ; Molnár, J. ; Mulhovo, Silva ; Rosário, Virgílio E. ; Ferreira, Maria José U. / New potent P-glycoprotein modulators with the cucurbitane scaffold and their synergistic interaction with doxorubicin on resistant cancer cells. In: Bioorganic and Medicinal Chemistry. 2009 ; Vol. 17, No. 19. pp. 6942-6951.
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