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 |
PubChem CID |
|
| UNII | |
CompTox Dashboard (EPA) |
|
| |
| |
| 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).
| |
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]
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.[5]
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,[6][7] including beta-lactam based compounds.[8]
Pharmacokinetics
[edit]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
[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
- ↑ "Selleck Chem". www.selleckchem.com. Retrieved 25 April 2025.
- ↑ 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" (PDF).
- ↑ 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. hdl:20.500.12684/4730. 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.
- ↑ Xu, Xiao-Ping; Wu, Xiao-Dong; Liang, Gui-Lun; Huang, Wen-Sheng; Wang, Li; Jing, Hai-Ying; Zhong, Shi-Long (1 June 2012). "Pharmacokinetics, excretion, and distribution of combretastatin A4 phosphate in rats". Die Pharmazie. 67 (6): 529–533. doi:10.1691/ph.2012.1647.