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, 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.
Kardono
L B
LB
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago 60612.
Angerhofer
C K
CK
Tsauri
S
S
Padmawinata
K
K
Pezzuto
J M
JM
Kinghorn
A D
AD
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000962:Antimalarials; D000970:Antineoplastic Agents