Combretastatin A-4 Explained

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.^{[1] [2]}

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.^[3]

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,^{[4] [5]} including beta-lactam based compounds.^[6]

See also

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

Notes and References

1. Determination of Combretastatin A-4 in Combretum leprosum. SCN Queiroz, MR Assalin, S Nobre, IS Melo, RM Moraes, VL Ferracini and AL Cerdeira, Planta Med, 2010, volume 76, pages 53,
2. Gill. Rupinder. Kaur. Ramandeep. Kaur. Gurneet. Rawal. Ravindra. Shah. Anamik. Bariwal. Jitender. A Comprehensive Review on Combretastatin Analogues as Tubulin Binding Agents. Current Organic Chemistry. 18. 19. 2462–2512. 10.2174/138527281819141028114428. 2014.
3. http://www.cell.com/chem/pdf/S2451-9294(16)30270-4.pdf Structural Basis of cis- and trans-Combretastatin Binding to Tubulin. Gaspari. 2017
4. Synthesis and biological evaluation of Combretastatin A-4 derivatives containing a 3'-O-substituted carbonic ether moiety as potential antitumor agents. . Chemistry Central Journal. 7. 1. 179. Ma. et al . 2013 . 10.1186/1752-153X-7-179 . 24304592. 3878987 . free .
5. Richter. Michael. Boldescu. Veaceslav. Graf. Dominik. Streicher. Felix. Dimoglo. Anatoli. Bartenschlager. Ralf. Klein. Christian D.. 2019. Synthesis, Biological Evaluation, and Molecular Docking of Combretastatin and Colchicine Derivatives and their hCE1-Activated Prodrugs as Antiviral Agents. ChemMedChem. en. 14. 4. 469–483. 10.1002/cmdc.201800641. 30605241. 1860-7187. free.
6. O'Boyle. N. Miriam Carr . Lisa M. Greene . Orla Bergin . Seema M. Nathwani . Thomas McCabe . David G. Lloyd . Daniela M Zisterer . Mary J. Meegan . Journal of Medicinal Chemistry. 2010. 53. 24. 8569–8584. 10.1021/jm101115u . 21080725 . Synthesis and evaluation of azetidinone analogues of combretastatin A-4 as tubulin targeting agents.. 2262/81779. free .