Planta Med 2011; 77 - PM195
DOI: 10.1055/s-0031-1282953

Triterpenoids as inhibitors of Plasmodium liver-stage development

C Ramalhete 1, A Cruz 2, S Mulhovo 3, M Prudêncio 2, MU Ferreira 1
  • 1Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmácia, Universidade de Lisboa, Av. das Forças Armadas, 1600–083, Lisboa, Portugal
  • 2Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, 1649–028, Lisboa, Portugal
  • 3Departamento de Ciências Agro-Pecuárias, Escola Superior Técnica, Universidade Pedagógica, Campus de Lhanguene, Av. de Moçambique, 21402161 Maputo, Mozambique

Malaria is one of the foremost public health problems in Africa. It is endemic in 90 countries, affecting nearly 40% of the global population. The increasing prevalence of drug-resistant Plasmodium falciparum strains is one of the greatest challenges in malaria control. In order to overcome drug-resistance, new antimalarial drugs are urgently needed. Most of the available antimalarial agents kill blood stage parasites and only a limited number of drugs act on liver stages. In fact, the study of Plasmodium liver stage development has been hampered by limitations in the experimental approaches required to quantify hepatocyte infection by the parasite. Therefore, the development of new drugs targeting the Plasmodium liver stage represents an important and under-exploited site of intervention [1, 2].

Previously, bioassay-guided fractionation of the methanol extract of the aerial parts of Momordica balsamina L. led to the isolation of several cucurbitane-type triterpenoids. Several of those compounds and acylated derivatives displayed in vitro antimalarial activity against blood schizonts of chloroquine-sensitive and -resistant strains of Plasmodium falciparum [3–5]. In this study some of the isolated compounds from Momordica balsamina and several alkanoyl and aroyl ester derivatives were evaluated for their in vitro tissue-schizontocidal activity on Plasmodium berghei infected hepatoma cells. Inhibition of liver stage infection was determined by measuring the luminescence intensity in Huh-7 cells infected with a firefly luciferase-expressing P. berghei line, PbGFP-Luccon, as previously described [1]. Most of the compound tested displayed a dose-dependent antimalarial activity with IC50<5µM.

Keywords: Malaria, Plasmodium, liver-stage, Momordica balsamina

Acknowledgement: This study was supported by FCT, Portugal (SFRH/BD/22321/2005).

References: 1. Ploemen et al (2009) PloS One 4: e7881.

2. Prudêncio et al. (2008) Cell Microbiol 10: 218–24.

3. Ramalhete et al. (2009) Bioorg. Med Chem 17: 6942–51.

4. Ramalhete et al. (2010) Bioorg. Med Chem 18: 5254–60.

5. Ramalhete et al. (2011) Bioorg. Med Chem 19: 330–8.