Antimalarial compounds from Crinum Bulbispermum

Abstract

Malaria is caused by protozoan parasites of the genus Plasmodium, of which Plasmodium falciparum is the most widespread and dangerous. Around 800 000 children under the age of five die from malaria every year. An increase in resistance to previously effective drugs is also evident. This disease therefore has social and economical consequences. The isolation of antimalarial compounds from medicinal plants may provide the solution to an ever increasing demand for new effective antimalarial agents. Compounds with antimalarial activity also tend to have antimicrobial activity, thus when testing plants for antimalarial activity, it must be considered that they may also provide effective antimicrobial agents. Six plants were selected and 62 extracts of the different morphological plant parts were prepared, using Soxhlet extraction with petroleum ether, dichloromethane, ethyl acetate and ethanol consecutively. The antimalarial activity was assessed by employing the [3H] - hypoxanthine incorporation assay against the chloroquine-resistant Gambian FCR-3 strain of P. falciparum. The dichloromethane and ethyl acetate extracts of Crinum bulbispermum exhibited the most promising activity, with IC, values of 0.379 + 0.126 and 0.08 f 0.004 kg/ml respectively, and were selected for further study. Two acids, namely linoleic acid (24), oleic acid (25) and an alkaloid, namely lycorine (26) was isolated with column and thin layer chromatography and structures were elucidated by using nuclear magnetic resonance, mass and infrared spectrometry. The antimalarial activity of the isolated compounds (24 - 26) were assessed. The IC, value of the isolated compound lycorine (26) (0.0291 f 0.01 kg/ml) compares well to that of chloroquine (1) and quinine (2) (IC, values of 0.04 + 0.01 and 0.17 + 0.02 pg/ml, respectively). These compounds (24 - 26) were found to be relatively non-toxic as determined by an in vitro cellular toxicity assay. IC, values for toxicity were determined for the respective compounds (24 - 26) and lycorine (26) had the best toxicity index of > 15 000. Since this compound had such a high toxicity index it was regarded as suitable for further investigation as an antimalarial drug. Antimicrobial activity was assessed with the direct plate method and minimum inhibitory concentration values were determined. The best activity was observed for the alkaloid lycorine (26) against 6. subtilis. The isolated alkaloid lycorine (26) is not structurally related to any other antimalarial drug currently in use and could therefore be used as a lead compound for a new class of antimalarial drugs. The diverse chemistry of medicinal plants affords a viable source in the search for biologically active compounds.