Isolation, structure, synthesis, and antimitotic properties of combretastatins B-3 and B-4 from Combretum caffrum.
Further investigation of a CH2Cl2 fraction prepared from the South African tree Combretum caffrum for substances inhibitory to the murine P-388 lymphocytic leukemia (PS system) cell line has led to the isolation of two new bibenzyls, designated combretastatins B-3 and B-4, accompanied by the previously known bibenzyls 7, 8, and 9. The structure of each substance was ascertained by results of mass and nmr spectral analyses and confirmed by crystal structure determination (for 7) or synthesis. Combretastatins B-3 and B-4 gave PS ED50 values of 0.4 and 1.7 micrograms/ml, respectively, and bibenzyls 7, 8, and 9 were comparably cell growth inhibitory against the PS cell line with ED50 results of 1.7, 2.5, and 0.25 ug/ml, respectively. All the bibenzyls caused leukemia cells to accumulate in mitosis at cytotoxic drug concentrations; however, a wide range of in vitro activity against the protein tubulin (the major component of the mitotic spindle) was observed.
Pettit
G R
GR
Cancer Research Institute, Arizona State University, Tempe 85287.
Singh
S B
SB
Schmidt
J M
JM
Niven
M L
ML
Hamel
E
E
Lin
C M
CM
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000302:isolation & purification*; D001632:Bibenzyls / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology; D010946:Plants, Medicinal / Q000032:analysis*; D013267:Stilbenes; D014197:Trees / Q000032:analysis
D000972:Antineoplastic Agents, Phytogenic; D001632:Bibenzyls; D010936:Plant Extracts; D013267:Stilbenes; C056667:combretastatin B-4; C056668:combretastatin B-3