Abstract
BackgroundCarapa guianensis is a cultivable tree used by traditional health practitioners in the Amazon region to treat several diseases and particularly symptoms related to malaria. Abundant residual pressed seed material (RPSM) results as a by-product of carapa or andiroba oil production. The objective of this study was to evaluate the in vitro and in vivo anti-malarial activity and cytotoxicity of limonoids isolated from C. guaianensis RPSM.Methods6α-acetoxyepoxyazadiradione (1), andirobin (2), 6α-acetoxygedunin (3) and 7-deacetoxy-7-oxogedunin (4) (all isolated from RPSM using extraction and chromatography techniques) and 6α-hydroxy-deacetylgedunin (5) (prepared from 3) were evaluated using the micro test on the multi-drug-resistant Plasmodium falciparum K1 strain. The efficacy of limonoids 3 and 4 was then evaluated orally and subcutaneously in BALB/c mice infected with chloroquine-sensitive Plasmodium berghei NK65 strain in the 4-day suppressive test.ResultsIn vitro, limonoids 1-5 exhibited median inhibition concentrations (IC50) of 20.7-5.0 μM, respectively. In general, these limonoids were not toxic to normal cells (MRC-5 human fibroblasts). In vivo, 3 was more active than 4. At oral doses of 50 and 100 mg/kg/day, 3 suppressed parasitaemia versus untreated controls by 40 and 66%, respectively, evidencing a clear dose–response.Conclusion6α-acetoxygedunin is an abundant natural product present in C. guianensis residual seed materials that exhibits significant in vivo anti-malarial properties.Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-13-317) contains supplementary material, which is available to authorized users.
Highlights
Carapa guianensis is a cultivable tree used by traditional health practitioners in the Amazon region to treat several diseases and symptoms related to malaria
Carapa guiananesis seeds were collected at the National Institute for Amazon Research’s (INPA) Adolpho Ducke Forest Reserve located in Manaus, Amazonas State, Brazil from the areas beneath two trees identified by voucher specimens deposited previously in the INPA Herbarium under the accession numbers 192615 and 178658 [25]
Isolated and semi-synthetic limonoids 1-5 were fully characterized by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) one and twodimensional spectrometric techniques
Summary
Carapa guianensis is a cultivable tree used by traditional health practitioners in the Amazon region to treat several diseases and symptoms related to malaria. Natural products are the direct or indirect sources of most of the drugs introduced in the past 30 years [5]. Natural products from plants are a rich source of lead compounds for the development of new drugs against protozoan parasitic diseases such as malaria [6,7,8,9]. Further development gave rise to synthetic quinoline and artemisinin classes of antimalarials that form the basis of ACT. Artemisinin derivatives (e.g. sodium artesunate, arteether, dihydroartemisinin) and quinolines (e.g. chloroquine, primaquine) are the basis of malaria treatment worldwide. The Amazon region has a rich tradition of plant use for the treatment of malaria and a number of natural products have been isolated and semi-synthetic derivatives prepared exhibiting important in vitro and in vivo anti-malarial properties [11]
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