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This work was supported by grants from the Spanish Ministry of Science and Innovation (BIO2007-67885 and BIO2010-17039), the Research Teams Consolidation Programme of the UCM (Research Team 920267-Comunidad de Madrid) and the Iberoamerican CYTED network No. 210RT0398. CM is supported by the Universidad de Cartagena (Colombia) and the Alban Programme of High Level Scholarships for Latin America, fellowship E07D400516CO. PMG is supported by a postdoctoral fellowship from the Spanish Ministry of Education and Science. We thank Glaxo SmithKline for providing atovaquone. The excellent technical help of Susana Perez-Benavente is also aknowledged.

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Parasitostatic effect of maslinic acid. I. Growth arrest of Plasmodium falciparum intraerythrocytic stages

Publicado en:Malaria Journal. 10 82- - 2011-04-10 10(), DOI: 10.1186/1475-2875-10-82

Autores: Moneriz, Carlos; Marin-Garcia, Patricia; Garcia-Granados, Andres; Bautista, Jose M; Diez, Amalia; Puyet, Antonio

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Background: Natural products have played an important role as leads for the development of new drugs against malaria. Recent studies have shown that maslinic acid (MA), a natural triterpene obtained from olive pomace, which displays multiple biological and antimicrobial activities, also exerts inhibitory effects on the development of some Apicomplexan, including Eimeria, Toxoplasma and Neospora. To ascertain if MA displays anti-malarial activity, the main objective of this study was to asses the effect of MA on Plasmodium falciparum-infected erythrocytes in vitro.Methods: Synchronized P. falciparum-infected erythrocyte cultures were incubated under different conditions with MA, and compared to chloroquine and atovaquone treated cultures. The effects on parasite growth were determined by monitoring the parasitaemia and the accumulation of the different infective stages visualized in thin blood smears.Results: MA inhibits the growth of P. falciparum Dd2 and 3D7 strains in infected erythrocytes in, dose-dependent manner, leading to the accumulation of immature forms at IC50 concentrations, while higher doses produced nonviable parasite cells. MA-treated infected-erythrocyte cultures were compared to those treated with chloroquine or atovaquone, showing significant differences in the pattern of accumulation of parasitic stages. Transient MA treatment at different parasite stages showed that the compound targeted intra-erythrocytic processes from earlyring to schizont stage. These results indicate that MA has a parasitostatic effect, which does not inactivate permanently P. falciparum, as the removal of the compound allowed the infection to continueConclusions: MA displays anti-malarial activity at multiple intraerythrocytic stages of the parasite and, depending on the dose and incubation time, behaves as a plasmodial parasitostatic compound. This novel parasitostatic effect appears to be unrelated to previous mechanisms proposed for current anti-malarial drugs, and may be relevant to uncover new prospective plasmodial targets and opens novel possibilities of therapies associated to host immune response.

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