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Background  Several species of the genus  Aspidosperma  (Apocynaceae) are used for the treatment of human malaria in Brazil and other meso- and South American countries.    Methods  Ethanol extract from  Aspidosperma parvifolium  trunk bark was submitted to acid–base extractions leading to alkaloid and neutral fractions. The alkaloid fraction was chromatographed over a silica gel column. Ethanol extract, fractions and uleine were analysed by HPLC–DAD, UPLC-ESI–MS/MS and HPLC-ESI-MicroTOF-MS. The anti-malarial activity was assayed against resistant and sensitive chloroquine  Plasmodium falciparum  strains by microscopic, [ 3 H]-hypoxanthine incorporation and HRPII techniques. Cytotoxicity (CC 50 ) was evaluated against Vero and HepG2 cell lines by the MTT technique; selectivity indexes (SI = CC 50 /IC 50 ) were calculated.    Results  The major peak in the HPLC–DAD chromatograms of the ethanol extract, alkaloid and neutral fractions suggested the presence of uleine that was isolated from the alkaloid fraction by column chromatography and was characterized by spectroscopic methods. A total of 15 alkaloids, besides uleine, were identified in the alkaloid fraction by UPLC-DAD-ESI–MS/MS and HPLC-ESI-MicroTOF-MS. The ethanol extract from  Aspidosperma parvifolium  and the neutral fraction were moderately active against  P. falciparum  strains. The alkaloid fraction and uleine disclosed high anti-malarial activity against chloroquine-resistant  P. falciparum  strain (IC 50  < 1 µg/mL). The ethanol extract, neutral fraction and uleine showed low cytotoxicity against Vero and HepG2 cell lines (CC 50  > 300 µg/mL). The alkaloid fraction showed moderate cytotoxicity to HepG2 cell line (CC 50  = 74.4 µg/mL). High SI values (>10) were determined for all samples.    Conclusion  Ethanol extract from  Aspidosperma parvifolium  trunk bark afforded uleine that is the major constituent of the alkaloid fraction and disclosed a good in vitro anti-malarial activity. Moreover, 15 other indole alkaloids have been identified along with uleine.

Aspidosperma species as sources of anti-malarials: uleine is the major anti-malarial indole alkaloid from Aspidosperma parvifolium (Apocynaceae)