Antitumor Agents. 203. Carbazole Alkaloid Murrayaquinone A and Related Synthetic Carbazolequinones as Cytotoxic Agents

Murrayaquinone A (1) and murrayafoline A (3), isolated from the root bark of Murraya euchrestifolia, were identified as cytotoxic compounds. Murrayaquinone A (1) demonstrated significant cytotoxicity against SK-MEL-5 and Colo-205 cells, with ED50 values of 2.58 and 3.85 μg/mL, respectively. In contrast, 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 μg/mL. In total, 20 carbazole alkaloids (1−20), isolated previously by Furukawa et al. from various plant sources were also evaluated for their cytotoxic profiles in the NCI's human disease-oriented, 60-cell line, in vitro antitumor screening protocol. Compounds 3 and 15 showed potent cell-line selective cytotoxicity against MOLT-4 cells, with log GI50 values of −8.60 and −8.49 M, respectively, while 12 demonstrated better selectivity against the colon cancer subpanel. Moreover, synthetic 2-methyl- or 3-methyl-carbazolequinone derivatives with various substituents in the A-ring were evaluated against KB, SK-MEL-5, Colo-205, and HCT-8 tumor cells. 6-Methoxy- (21), 6-methyl- (22), and 6-chloro- (24) 3-methyl-carbazolequinones demonstrated significant cytotoxicity against SK-MEL-5 cells, with ED50 values of 0.55, 0.66, and 0.83 μg/mL, respectively. Compounds 21 and 22 were also significantly cytotoxic toward KB cells, with ED50 values of 0.76 and 0.92 μg/mL, respectively, and 21 displayed a similar level of toxicity against Colo-205 cells (ED50 0.87 μg/mL).