Antineoplastic agents. 291. Isolation and synthesis of combretastatins A-4, A-5, and A-6(1a)
The antineoplastic constituents of Combretum caffrum (Eckl. and Zeyh) Kuntze (Combretaceae family), a species indigenous to South Africa, have been investigated. Subsequently we isolated a series of closely related bibenzyls, stilbenes, and phenanthrenes from C. caffrum. Some of the stilbenes proved to be potent antimitotic agents which inhibited both tubulin polymerization and the binding of colchicine to tubulin. Combretastatin A-4 has been shown to be the most potent cancer cell growth inhibitor of the series. Presently this cis-stilbene is the most effective inhibitor of colchicine binding to tubulin and the simplest natural product yet described with such potent antitubulin effects. Combretastatin A-4, A-5, and A-6 were also found to inhibit growth of Neisseria gonorrhoeae. Details of the isolation and syntheses of combretastatins A-4 (2a), A-5 (2c), and A-6 (3a) have been described.
Pettit
G R
GR
Cancer Research Institute, Arizona State University, Tempe 85287-1604, USA.
Singh
S B
SB
Boyd
M R
MR
Hamel
E
E
Pettit
R K
RK
Schmidt
J M
JM
Hogan
F
F
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D008826:Microbial Sensitivity Tests; D009344:Neisseria gonorrhoeae / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D013267:Stilbenes / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C093618:combretastatin A5; C058728:fosbretabulin