Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4.
The African tree Combretum caffrum (Combretacae) has been found to contain a powerful inhibitor of tubulin polymerization (IC50 2-3 microM), the growth of murine lymphocytic leukemia (L 1210 and P 388 with ED50 approximately 0.003 microM and human colon cancer cell lines [(e.g. LoVo (ED50 = 0.005 microgram/ml), HT 29 (ED50 0.02 microgram/ml, Colo 205 (ED50 = 0.07 microgram/ml), DLD-1 (ED50 = 0.005 microgram/ml) and HCT-15 (ED50 = 0.0009 microgram/ml] designated combretastatin A-4 (1c). The structure assigned by spectral techniques was confirmed by synthesis.
Pettit
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GR
Cancer Research Institute, Arizona State University, Tempe 85287.
Singh
S B
SB
Hamel
E
E
Lin
C M
CM
Alberts
D S
DS
Garcia-Kendall
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D
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic; D001632:Bibenzyls / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D010936:Plant Extracts; D013267:Stilbenes; D050257:Tubulin Modulators; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D001632:Bibenzyls; D010936:Plant Extracts; D013267:Stilbenes; D050257:Tubulin Modulators; C058728:fosbretabulin