Antimalarial Benzylisoquinoline Alkaloid from the Rainforest Tree Doryphora sassafras

Mass-directed isolation of the CH(2)Cl(2)/MeOH extract of Doryphora sassafras resulted in the purification of a new benzylisoquinoline alkaloid, 1-(4-hydroxybenzyl)-6,7-methylenedioxy-2-methylisoquinolinium trifluoroacetate (1), and the known aporphine alkaloid (S)-isocorydine (2). The structures of 1 and 2 were determined by 1D and 2D NMR and MS data analyses. The compounds were isolated during a drug discovery program aimed at identifying new antimalarial leads from a prefractionated natural product library. When tested against two different strains of the parasite Plasmodium falciparum (3D7 and Dd2), 1 displayed IC(50) values of 3.0 and 4.4 microM, respectively. Compound 1 was tested for cytotoxicity toward a human embryonic kidney cell line (HEK293) and displayed no activity at 120 microM.