Combretastatin A-4

Chemical compound From Wikipedia, the free encyclopedia

Combretastatin A-4 is a combretastatin and a stilbenoid. It can be isolated from Combretum afrum, the Eastern Cape South African bushwillow tree or in Combretum leprosum, the mofumbo, a species found in Brazil.[3][4]

Quick facts Names, Identifiers ...
Combretastatin A-4
Names
Preferred IUPAC name
2-Methoxy-5-[(1Z)-2-(3,4,5-trimethoxyphenyl)ethen-1-yl]phenol
Other names
Combretastatin A4
CA-4
1-(3,4,5-Trimethoxyphenyl)-2-(3′-hydroxy-4′-methoxyphenyl)ethene
3,4,5-Trimethoxy-3′-hydroxy-4′-methoxystilbene
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.159.667 Edit this at Wikidata
UNII
  • InChI=1S/C18H20O5/c1-20-15-8-7-12(9-14(15)19)5-6-13-10-16(21-2)18(23-4)17(11-13)22-3/h5-11,19H,1-4H3/b6-5- checkY
    Key: HVXBOLULGPECHP-WAYWQWQTSA-N checkY
  • COC1=C(C=C(C=C1)C=CC2=CC(=C(C(=C2)OC)OC)OC)O
Properties
C18H20O5
Molar mass 316.34 g/mol
Melting point 116 °C (241 °F; 389 K)[1]
insoluble
Solubility in DMSO, Ethanol DMSO : 63 mg/mL, Ethanol : 34 mg/mL[2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Function

Tubulin represents a potent target in cancer chemotherapy, given its role in cell division. Combretastatin is a naturally occurring well known tubulin polymerization inhibitor. Combretastatin A-4 comes in two stereoisomers (cis (shown top right), and trans); The cis form binds much better to the 'colchicine' site on tubulin to inhibit polymerization.[5]

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.[citation needed]

A large number of synthetic derivatives have been reported,[6][7] including beta-lactam based compounds.[8]

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.[9]

See also

  • Ombrabulin, a combretastatin A-4 derivative in clinical trials for treatment of cancer

References

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