Combretastatin A-4 is a
combretastatin and a
stilbenoid
Stilbenoids are hydroxylated derivatives of stilbene. They have a C6–C2–C6 structure. In biochemical terms, they belong to the family of phenylpropanoids and share most of their biosynthesis pathway with Chalconoid, chalcones. Most stilbenoids ...
. It can be isolated from ''
Combretum afrum
''Combretum afrum'', commonly known as Cape bushwillow, is a species of tree native to South Africa. It is endemic to the Cape Provinces.
Biochemistry
In ''C. afrum'', combretastatins A-1, A-4 and B-1 can be found.
Taxonomy
The etymology ...
'', the Eastern Cape South African bushwillow tree or in ''
Combretum leprosum'', the mofumbo, a species found in Brazil.
Function
Tubulin
Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytosk ...
represents a potent target in cancer
chemotherapy
Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
, given its role in cell division. Combretastatin is a naturally occurring well known tubulin polymerization inhibitor. Combretastatin A-4 comes in two
stereoisomer
In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...
s (
cis (shown top right), and trans); The cis form binds much better to the 'colchicine' site on tubulin to inhibit polymerization.
Derivatives
Combretastatin A-4 is the active component of
combretastatin A-4 phosphate, a prodrug designed to damage the vasculature (blood vessels) of cancer tumors causing central necrosis.
A large number of synthetic
derivatives have been reported,
including
beta-lactam based compounds.
Pharmacokinetics
CA4 has a half life of 1.8-4.2h in humans. CA4P(a prodrug) has a half life of 0.22-0.36h in humans.
See also
*
Ombrabulin, a combretastatin A-4 derivative in clinical trials for treatment of cancer
References
{{stilbenes
Combretastatins
Stilbenoids
Experimental cancer drugs