Cytotoxic and Antimalarial Constituents of the Roots of Eurycoma longifolia

• Published in: Journal of natural products (Washington, D.C.) D.C.), 1991-09, Vol.54 (5), p.1360-1367
• Main Authors: Kardono, Leonardus B. S, Angerhofer, Cindy K, Tsauri, Soefjan, Padmawinata, Kosasih, Pezzuto, John M, Kinghorn, A. Douglas
• Format: Article
• Language: English
• Subjects: agentes antineoplasticos; alcaloide; alcaloides; alkaloids; Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Antimalarials - chemistry; Antimalarials - isolation & purification; Antimalarials - pharmacology; antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; antiprotozoaire; antiprotozoal agents; Biological and medical sciences; carcinoma; carcinome; cell culture; cultivo de celulas; culture de cellule; Drug Screening Assays, Antitumor; fitotoxicidad; General pharmacology; Humans; leucemia; leucemie; leukaemia; Leukemia P388 - drug therapy; Magnetic Resonance Spectroscopy; Medical sciences; medicament cytostatique; medicamentos contra protozoarios; Molecular Structure; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; phytotoxicite; phytotoxicity; plasmodium falciparum; Plasmodium falciparum - drug effects; racine; raices; roots; simaroubaceae; substance toxique; sustancias toxicas; toxic substances; triterpenoide; triterpenoidos; triterpenoids; Tumor Cells, Cultured
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np50077a020

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, 9-methoxycanthin-6-one-N-oxide, 9-hydroxycanthin-6-one, and 9-hydroxycanthin-6-one-N-oxide, and one quassinoid, eurycomanone, 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 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 and 7-methoxy-beta-carboline-1-propionic acid, 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.