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

Abstract

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 ED(50) values of 2.58 and 3.85 microg/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 ED(50) values ranging from 5.31 to 7.52 microg/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 GI(50) 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 ED(50) values of 0.55, 0.66, and 0.83 microg/mL, respectively. Compounds 21 and 22 were also significantly cytotoxic toward KB cells, with ED(50) values of 0.76 and 0.92 microg/mL, respectively, and 21 displayed a similar level of toxicity against Colo-205 cells (ED(50) 0.87 microg/mL).

A benzoisofuranone derivative and carbazole alkaloids from Murraya koenigii and their antimicrobial activity

“…Murrayaquinone and murrayafoline-A from the root of M. euchrestifolia (Furukawa et al, 1985) have been found to have weak but fairly selective cytotoxic activity against a panel of about 60 tumour cell lines (Itoigawa et al, 2000). Itoigawa et al (2000) also found that several other natural and synthetic carbazoles had more selective cytotoxicities.…”

“…Murrayaquinone and murrayafoline-A from the root of M. euchrestifolia (Furukawa et al, 1985) have been found to have weak but fairly selective cytotoxic activity against a panel of about 60 tumour cell lines (Itoigawa et al, 2000). Itoigawa et al (2000) also found that several other natural and synthetic carbazoles had more selective cytotoxicities. The activities of the carbazole alkaloids from M. koenigii described here would seem to justify some of the folk medicinal uses of the plant, for example in the treatment of diarrhoea, dysentery and against biting insects (Kirtikar et al, 1993;Yusuf et al, 1994).…”

2-(4,5-Dimethoxy-2-nitrophenyl)-4-methoxy-3-methyl-9-phenylsulfonyl-9H-carbazole

“…It has been reported that carbazole derivatives exhibit various biological activities such as antitumor (Itoigawa et al, 2000), anti-inflammatory and antimutagenic (Ramsewak et al, 1999). Carbazole derivatives also exhibit electroactivity and luminenscence and are considered to be potential candidates for electronic applications such as colour displays, organic semiconductors, laser and solar cells (Friend et al, 1999;Zhang et al, 2004).…”

Synthesis and Cytotoxic Activity Evaluation of Novel Derivatives of Murrayafoline A

“…A number of natural carbazole alkaloids were recognized to exhibit potential biological activities such as antimicrobial [1,2], anti-HIV [3], anticancer [4,5,6] activities. Among them, several compounds were used as drugs for treatment of cancer [7].…”