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

J Nat Prod. 2000 Jul;63(7):893-7. doi: 10.1021/np000020e.

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).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Benzoquinones / chemistry
  • Benzoquinones / pharmacology*
  • Carbazoles / chemistry
  • Carbazoles / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Plants / chemistry
  • Quinones / chemistry
  • Quinones / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Benzoquinones
  • Carbazoles
  • Quinones
  • murrayaquinone A