Karavilagenin C derivatives as antimalarials

Cátia Ramalhete, Dinora Lopes, Joseph Molnár, Silva Mulhovo, Virgílio E. Rosário, Maria José U. Ferreira

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17 Citations (Scopus)

Abstract

Karavilagenin C (1), a cucurbitane-type triterpenoid, previously isolated from the aerial parts of Momordica balsamina, was acylated with different alkanoyl, aroyl and cinnamoyl chlorides/anydrides, yielding ten new mono or diesters, karavoates F (7) and H-P (8-16). Furthermore, the new compound cucurbalsaminol C (17) was isolated from the same plant. Their structures were assigned by spectroscopic methods, including 2D NMR experiments. Compounds 1 and 17 and the acyl derivatives 8-16 along with other five esters (2-6, karavoates A-E), previously prepared from 1, were evaluated for their in vitro antimalarial activity against the chloroquine-sensitive (3D7) and the chloroquine-resistant (Dd2) strains of Plasmodium falciparum. Compound 1 exhibited a moderate activity and 17 was inactive. However, a remarkable antiplasmodial activity was observed for most of karavilagenin C alkanoyl and monoaroyl/cynamoyl derivatives. Karavoates B, D, E, I, and M were the most active, displaying IC50 values similar to those found for chloroquine, particularly against the resistant strain (IC50 <0.6 μM). Structure-activity relationships (SAR) are discussed. Moreover, the preliminary toxicity toward human cells of compounds 1-17 was also evaluated in breast cancer cell line (MCF-7). Most of the esters showed no toxicity, displaying, in general, much higher selectivity index values than those obtained for the parent compound.

Original languageEnglish
Pages (from-to)330-338
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

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Keywords

  • Antimalarial activity
  • Cucurbitaceae
  • Cucurbitane-type triterpenes
  • Karavilagenin C
  • Momordica balsamina
  • Plasmodium falciparum

ASJC Scopus subject areas

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

Cite this

Ramalhete, C., Lopes, D., Molnár, J., Mulhovo, S., Rosário, V. E., & Ferreira, M. J. U. (2011). Karavilagenin C derivatives as antimalarials. Bioorganic and Medicinal Chemistry, 19(1), 330-338. https://doi.org/10.1016/j.bmc.2010.11.015