Combretastatin A-4
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| Names | |
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| 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)
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| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.159.667 |
PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C18H20O5 | |
| Molar mass | 316.34 g/mol |
| Melting point | 116 °C (241 °F; 389 K)[1] |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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.[2][3]
Function
[edit]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.[4]
Derivatives
[edit]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,[5][6] including beta-lactam based compounds.[7]
See also
[edit]- Ombrabulin, a combretastatin A-4 derivative in clinical trials for treatment of cancer
References
[edit]- ^ Pettit, G. R.; Sheo Bux Singh Boyd; M. R. Hamel, E. (1995), "Antineoplastic Agents. 291. Isolation and Synthesis of Combretastatins A-4, A-5, and A-6", Journal of Medicinal Chemistry, 38 (10): 1666–1672, doi:10.1021/jm00010a011, PMID 7752190
- ^ 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, doi:10.1055/s-0030-1251815
- ^ Gill, Rupinder; Kaur, Ramandeep; Kaur, Gurneet; Rawal, Ravindra; Shah, Anamik; Bariwal, Jitender (2014). "A Comprehensive Review on Combretastatin Analogues as Tubulin Binding Agents". Current Organic Chemistry. 18 (19): 2462–2512. doi:10.2174/138527281819141028114428.
- ^ Structural Basis of cis- and trans-Combretastatin Binding to Tubulin. Gaspari. 2017
- ^ Ma; et al. (2013). "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. doi:10.1186/1752-153X-7-179. PMC 3878987. PMID 24304592.
- ^ 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. 14 (4): 469–483. doi:10.1002/cmdc.201800641. ISSN 1860-7187. PMID 30605241.
- ^ O'Boyle, N; Miriam Carr; Lisa M. Greene; Orla Bergin; Seema M. Nathwani; Thomas McCabe; David G. Lloyd; Daniela M Zisterer; Mary J. Meegan (2010). "Synthesis and evaluation of azetidinone analogues of combretastatin A-4 as tubulin targeting agents". Journal of Medicinal Chemistry. 53 (24): 8569–8584. doi:10.1021/jm101115u. hdl:2262/81779. PMID 21080725.