Silvestrol

Silvestrol is a natural product from the flavagline family, with a cyclopenta[b] benzofuran core structure and an unusual dioxane ether side chain, which is found in the bark of trees from the genus Aglaia, especially Aglaia silvestris and Aglaia foveolata.[1]

Silvestrol
Identifiers
  • methyl (1R,2R,3S,3aR,8bS)-6-[[(2S,3R,6R)-6-[(1R)-1,2-dihydroxyethyl]-3-methoxy-1,4-dioxan-2-yl]oxy]-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-cyclopenta[b] [1]benzofuran-2-carboxylate
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
Chemical and physical data
FormulaC34H38O13
Molar mass654.7 g·mol−1
3D model (JSmol)
  • CO[C@H]1[C@@H](O[C@H](CO1)[C@@H](CO)O)OC2=CC3=C(C(=C2)OC)[C@@]4([C@@H]([C@@H]([C@H]([C@@]4(O3)C5=CC=C(C=C5)OC)C6=CC=CC=C6)C(=O)OC)O)O
  • InChI=1S/C34H38O13/c1-40-20-12-10-19(11-13-20)34-27(18-8-6-5-7-9-18)26(30(38)42-3)29(37)33(34,39)28-23(41-2)14-21(15-24(28)47-34)45-32-31(43-4)44-17-25(46-32)22(36)16-35/h5-15,22,25-27,29,31-32,35-37,39H,16-17H2,1-4H3/t22-,25-,26-,27-,29-,31-,32-,33+,34+/m1/s1
  • Key:GVKXFVCXBFGBCD-QKDMMWSPSA-N

Bioactivity

It acts as a potent and selective inhibitor of the RNA helicase enzyme eIF4A, and has both broad-spectrum antiviral activity against diseases such as Ebola and coronaviruses, [2][3][4][5][6] and anti-cancer properties,[7][8] which makes it of considerable interest in medical research. However, as it cannot be extracted from tree bark in commercial amounts and is prohibitively complex to produce synthetically,[9] practical applications have focused more on structurally simplified analogues such as CR-31-B.[10]

See also

References
  1. Pan L, Woodard JL, Lucas DM, Fuchs JR, Kinghorn AD (July 2014). "Rocaglamide, silvestrol and structurally related bioactive compounds from Aglaia species". Natural Product Reports. 31 (7): 924–39. doi:10.1039/c4np00006d. PMC 4091845. PMID 24788392.
  2. Biedenkopf N, Lange-Grünweller K, Schulte FW, Weißer A, Müller C, Becker D, et al. (January 2017). "The natural compound silvestrol is a potent inhibitor of Ebola virus replication". Antiviral Research. 137: 76–81. doi:10.1016/j.antiviral.2016.11.011. PMID 27864075. S2CID 205577158.
  3. Elgner F, Sabino C, Basic M, Ploen D, Grünweller A, Hildt E (March 2018). "Inhibition of Zika Virus Replication by Silvestrol". Viruses. 10 (4): 149. doi:10.3390/v10040149. PMC 5923443. PMID 29584632.
  4. Müller C, Schulte FW, Lange-Grünweller K, Obermann W, Madhugiri R, Pleschka S, et al. (February 2018). "Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses". Antiviral Research. 150: 123–129. doi:10.1016/j.antiviral.2017.12.010. PMC 7113723. PMID 29258862.
  5. Henss L, Scholz T, Grünweller A, Schnierle BS (October 2018). "Silvestrol Inhibits Chikungunya Virus Replication". Viruses. 10 (11): 592. doi:10.3390/v10110592. PMC 6266838. PMID 30380742.
  6. Pillaiyar T, Meenakshisundaram S, Manickam M (April 2020). "Recent discovery and development of inhibitors targeting coronaviruses". Drug Discovery Today. 25 (4): 668–688. doi:10.1016/j.drudis.2020.01.015. PMC 7102522. PMID 32006468.
  7. Kogure T, Kinghorn AD, Yan I, Bolon B, Lucas DM, Grever MR, Patel T (2013). "Therapeutic potential of the translation inhibitor silvestrol in hepatocellular cancer". PLOS ONE. 8 (9): e76136. Bibcode:2013PLoSO...876136K. doi:10.1371/journal.pone.0076136. PMC 3784426. PMID 24086701.
  8. Pelletier J, Graff J, Ruggero D, Sonenberg N (January 2015). "Targeting the eIF4F translation initiation complex: a critical nexus for cancer development". Cancer Research. 75 (2): 250–63. doi:10.1158/0008-5472.CAN-14-2789. PMC 4299928. PMID 25593033.
  9. El Sous M, Khoo ML, Holloway G, Owen D, Scammells PJ, Rizzacasa MA (2007). "Total synthesis of (-)-episilvestrol and (-)-silvestrol". Angewandte Chemie. 46 (41): 7835–8. doi:10.1002/anie.200702700. PMID 17823902.
  10. Müller C, Obermann W, Schulte FW, Lange-Grünweller K, Oestereich L, Elgner F, et al. (January 2020). "Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (-) and the eIF4A-inhibitor Silvestrol". Antiviral Research. 175: 104706. doi:10.1016/j.antiviral.2020.104706. PMC 7114339. PMID 31931103.
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