Antitumor agents. 203. Carbazole alkaloid murrayaquinone A and related synthetic carbazolequinones as cytotoxic agents

Citation
M. Itoigawa et al., Antitumor agents. 203. Carbazole alkaloid murrayaquinone A and related synthetic carbazolequinones as cytotoxic agents, J NAT PROD, 63(7), 2000, pp. 893-897
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Agricultural Chemistry","Pharmacology & Toxicology
Journal title
JOURNAL OF NATURAL PRODUCTS
ISSN journal
0163-3864 → ACNP
Volume
63
Issue
7
Year of publication
2000
Pages
893 - 897
Database
ISI
SICI code
0163-3864(200007)63:7<893:AA2CAM>2.0.ZU;2-O
Abstract
Murrayaquinone A (1) and murrayafoline A (3), isolated from the root bark o f Murraya euchrestifolia, were identified as cytotoxic compounds. Murrayaqu inone A (1) demonstrated significant cytotoxicity against SK-MEL-5 and Colo -205 cells, with ED50 values of 2.58 and 3.85 mu g/mL, respectively. In con trast, murrayafoline A (3) exhibited marginal or weak cytotoxicity against SK-MEL-5, Colo-205, HCT-8, KB, and A-549 tumor cell lines, with ED50 values ranging from 5.31 to 7.52 mu g/mL. In total, 20 carbazole alkaloids (1-20) , isolated previously by Furukawa et al. from various plant sources were al so evaluated for their cytotoxic profiles in the NCI's human disease-orient ed, 60-cell, line, in vitro antitumor screening protocol. Compounds 3 and 1 5 showed potent cell-line selective cytotoxicity against MOLT-4 cells, with log GI(50) values of -8.60 and -8.49 M, respectively, while 12 demonstrate d better selectivity against the colon cancer subpanel. Moreover, synthetic 2-methyl- or 3-methyl-carbazolequinone derivatives with various substituen ts in the A-ring were evaluated against ICE, SK-MEL-5, Colo-205, and HCT-8 tumor cells. 6-Methoxy- (21), 6-methyl- (22), and 6-chloro- (24) 3-methyl-c arbazolequinones demonstrated significant cytotoxicity against SK-MEL-5 cel ls, with ED50 values of 0.55, 0.66, and 0.83 mu g/mL, respectively. Compoun ds 21 and 22 were also significantly cytotoxic toward KB cells, with ED50 v alues of 0.76 and 0.92 mu g/mL, respectively, and 21 displayed a similar le vel of toxicity against Colo-205 cells (ED50 0.87 mu g/mL).