Combretum caffrum

Combretastatins are a class of compounds originally derived from the African Willow tree (Combretum caffrum) and are powerful reversible inhibitors of tubulin polymerization. This class of molecules has been shown to bind to the colchicine binding site of tubulin, by the same mode of action as mentioned above (Sect. 1.2). Combretastatins consist of a ris-slilbcnc core structure. To date, there have been several compounds that have shown promise as potential anticancer drugs. However, development of these compounds as anticancer agents is limited by issues of chemical stability, bioavailibilty, toxicity, and solubility. 

Combretastatin A4 phosphate (72) is a phosphate prodrug of combretastatin A4, a c/s-stilbene, isolated from Combretum caffrum (66). Combretastatin A4 is one of the many combretas-tatins that inhibits tubulin polymerization (67), shows efficacy against solid tumor, is a vascular targeting agent that blocks the blood supply to solid tumors, and is in Phase II/III clinical development for the treatment of various types of tumors as a vascular targeting agent (68-71). 

The combretastatins are a group of antimitotic agents isolated from the bark of the South African tree Combretum caffrum. A novel and highly stereoselective total synthesis of both the c/s and trans isomers of combretastatin A-4 was developed by J.A. Hadfield and co-workers.The (Z)-stereoisomer was prepared using the Perkin reaction as the key step in which 3,4,5-trimethoxyphenylacetic acid and 3-hydroxy-4-methoxbenzaldehyde was heated with triethylamine and acetic anhydride at reflux for several hours. The a,p-unsaturated acid was isolated in good yield after acidification and had the expected ( ) stereochemistry. Decarboxylation of this acid was effected by heating it with copper powder in quinoline to afford the natural product (Z)-combretastatin A-4. 

Epothilones A and B are promising anticancer agents that bind to microtubules in the cell in the same way that paclitaxel (Taxol) does and are more potent.410 Paclitaxel was obtained first from the bark of the Pacific yew (Taxus brevifolia).4n Widespread extraction of the compound from this source could have wiped out the species. Fortunately, it can now be extracted from the needles of more common yews or produced in tissue culture. (See Sec II.C on tissue culture.) Forskolin is a diterpene, from the roots of Coleus forskohlii, that lowers blood pressure.412 Him-bacine, from an Australian pine tree, offers a potential treatment for Alzheimer s disease.413 Combretastatin, from the bark of the African bush willow, Combretum caffrum, cuts the flow of blood to tumors, causing 95% of the cancer cells to die in 24 h, but does not harm healthy blood vessels.414... 

A second group of tubulin inhibitors is represented by compounds exhibiting the combretastatin structure. Combretastatin (5) itself, as well as combretastatins A-l (5a), A-4 (5b) and A-2 (5d), have first been extracted from a South African tree Combretum caffrum by Pettit et al., depicting affinity to the colchicine binding site [28], Syntheses of various analogues of this simple molecule, thereafter, have been reported [16,29, 30] (see also Scheme 1). 

Combretastatins A-l, A-4, B-l belong to a class of natural products isolated from the South African tree Combretum caffrum [3]. 

Combretastatins. Antineoplastic compounds from the South African tree Combretum caffrum (Com-bretaceae) which has many uses in traditional medicine. C. caffrum contains stilbenes, bibenzyls, phenanthrenes, and diaryl ethers such as the cytotoxic C.D2 which are grouped together under the name C. 

Combretastatins, a series of bioactive stilbenes (combretastatin A series), bibenzyls (B series), phenanthrenes (C series), and macrocycUc lactone (D series), were obtained from the African wiUow tree Combretum caffrum (Combretaceae). Among them, the A series of combretastatins belonging to stilbenes, including combretastatins A-1 to A-6 2—7, are found to be tubulin polymerization inhibitors. 

Di-Me ether [116518-75-3]. H3,4-Dihydroxyphenyl)-2-(3,5-dimethoxyphenyl)ethane. Combretastatin B4 Ci Hig04 M 274.316 Constit. of Combretum caffrum. Viscous oil. 

Constit. of Combretum caffrum. Powder (Et0H/Et20). Mp 113-115°. 

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