Antiplasmodial Alkaloids from the Stem Bark of Strychnos malacoclados.

From the stem bark of STRYCHNOS MALACOCLADOS, one new bisindole alkaloid, 3-hydroxylongicaudatine Y ( 1), was isolated along with the known alkaloids vomicine ( 2), bisnordihydrotoxiferine ( 3), divarine ( 4), longicaudatine ( 5), longicaudatine Y ( 6), and longicaudatine F ( 7). All the compounds were tested for their antimalarial activity against the chloroquine-sensitive 3D7 and -resistant W2 strains of PLASMODIUM FALCIPARUM. Longicaudatine was the most active compound with IC (50) values of 0.682 and 0.573 microM, respectively. The activity of compounds 1, 3, 4, 6, and 7 against the two strains ranged from 1.191 to 6.220 microM and 0.573 to 21.848 microM, respectively. Vomicine ( 2), the only monomer isolated, was inactive. The alkaloids of the longicaudatine-type ( 1, 5- 7) were more active than those of the caracurine-type ( 3- 4). The presence of the ether bridge in the molecule seems to increase the antiplasmodial activity. Compounds 1, 5, and 7 were tested against the WI-38 human fibroblast cell line. Longicaudatine was the most cytotoxic compound with an IC (50) of 2.721 microM. Longicaudatine F was 40-46 times more active against the two strains of P. FALCIPARUM than against the human fibroblasts and was thus considered as the more selective alkaloid. The structures of the compounds were determined based on the analysis of their spectral data.