Chemistry:Combretastatin A-4
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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 | |
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3D model (JSmol)
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| Properties | |
| C18H20O5 | |
| Molar mass | 316.34 g/mol |
| Melting point | 116 °C (241 °F; 389 K)[2] |
| insoluble | |
| Solubility in DMSO, Ethanol | DMSO : 63 mg/mL, Ethanol : 34 mg/mL[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.[3][4]
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
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
- ↑ "Selleck Chem". https://www.selleckchem.com/products/combretastatin-a4.html.
- ↑ 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". http://www.cell.com/chem/pdf/S2451-9294(16)30270-4.pdf.
- ↑ Ma (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. 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" (in en). 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 et al. (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. PMID 21080725.
- ↑ Xu, Xiao-Ping; Wu, Xiao-Dong; Liang, Gui-Lun; Huang, Wen-Sheng; Wang, Li; Jing, Hai-Ying; Zhong, Shi-Long (2012-06-01). "Pharmacokinetics, excretion, and distribution of combretastatin A4 phosphate in rats". Die Pharmazie 67 (6): 529–533. doi:10.1691/ph.2012.1647. https://www.ingentaconnect.com/content/govi/pharmaz/2012/00000067/00000006/art00011.
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