STUDIES ON INDONESIAN MEDICINAL-PLANTS .4. CYTOTOXIC AND ANTIMALARIAL CONSTITUENTS OF THE ROOTS OF EURYCOMA-LONGIFOLIA

By bioactivity-directed fractionation, five cytotoxic constituents have been characterized from the roots of Eurycoma longifolia collected in Kalimantan, Indonesia. Four canthin-6-one alkaloids, namely, 9-methoxycanthin-6-one [1], 9-methoxycanthin-6-N-oxide [2], 9-hydroxycanthin-6-one [3], and 9-hydroxycanthin-6-one-N-oxide [4], and one quassinoid, eurycomanone [5], were found to be cytotoxic principles. Each of these compounds was evaluated against a panel of cell lines comprising a number of human cancer cell types [breast, colon, fibrosarcoma, lung, melanoma, KB, and KB-V1 (a multi-drug resistant cell line derived from KB)] and murine lymphocytic leukemia (P-388). The canthin-6-ones 1-4 were found to be active with all cell lines tested except for the KB-V1 cell line. Eurycomanone [5] was inactive against murine lymphocytic leukemia (P-388) but was significantly active against the human cell lines tested. Two additional isolates, the beta-carboline alkaloids beta-carboline-1-propionic acid [6] and 7-methoxy-beta-carboline-1-propionic acid [7], were not significantly active with these cultured cells. However, compounds 5 and 7 were found to demonstrate significant antimalarial activity as judged by studies conducted with cultured Plasmodium falciparum strains. The structures of the novel compounds 2-4 and 7 were established by spectral and chemical methods.