Combretastatin A-4

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]
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

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

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

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

References

  1. ^ 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
  2. ^ 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
  3. ^ 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.
  4. ^ Structural Basis of cis- and trans-Combretastatin Binding to Tubulin. Gaspari. 2017
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.