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
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).