Silvestrol

Silvestrol
Identifiers
	IUPAC name 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	697235-38-4 ;
PubChem CID	11787114;
ChemSpider	9961792;
UNII	KK3Y3KN5BV;
ChEBI	CHEBI:66484;
ChEMBL	ChEMBL555196;
Chemical and physical data
Formula	C34H38O13
Molar mass	654.7 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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 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;

Short description: Chemical compound

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]

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]

References

↑ "Rocaglamide, silvestrol and structurally related bioactive compounds from Aglaia species". Natural Product Reports 31 (7): 924–39. July 2014. doi:10.1039/c4np00006d. PMID 24788392.
↑ "The natural compound silvestrol is a potent inhibitor of Ebola virus replication". Antiviral Research 137: 76–81. January 2017. doi:10.1016/j.antiviral.2016.11.011. PMID 27864075.
↑ "Inhibition of Zika Virus Replication by Silvestrol". Viruses 10 (4): 149. March 2018. doi:10.3390/v10040149. PMID 29584632.
↑ "Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses". Antiviral Research 150: 123–129. February 2018. doi:10.1016/j.antiviral.2017.12.010. PMID 29258862.
↑ "Silvestrol Inhibits Chikungunya Virus Replication". Viruses 10 (11): 592. October 2018. doi:10.3390/v10110592. PMID 30380742.
↑ "Recent discovery and development of inhibitors targeting coronaviruses". Drug Discovery Today 25 (4): 668–688. April 2020. doi:10.1016/j.drudis.2020.01.015. PMID 32006468.
↑ "Therapeutic potential of the translation inhibitor silvestrol in hepatocellular cancer". PLOS ONE 8 (9): e76136. 2013. doi:10.1371/journal.pone.0076136. PMID 24086701. Bibcode: 2013PLoSO...876136K.
↑ "Targeting the eIF4F translation initiation complex: a critical nexus for cancer development". Cancer Research 75 (2): 250–63. January 2015. doi:10.1158/0008-5472.CAN-14-2789. PMID 25593033.
↑ "Total synthesis of (-)-episilvestrol and (-)-silvestrol". Angewandte Chemie 46 (41): 7835–8. 2007. doi:10.1002/anie.200702700. PMID 17823902.
↑ "Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (-) and the eIF4A-inhibitor Silvestrol". Antiviral Research 175: 104706. January 2020. doi:10.1016/j.antiviral.2020.104706. PMID 31931103.

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Original source: https://en.wikipedia.org/wiki/Silvestrol. Read more

[pmid24788392-1] "Rocaglamide, silvestrol and structurally related bioactive compounds from Aglaia species". Natural Product Reports 31 (7): 924–39. July 2014. doi:10.1039/c4np00006d. PMID 24788392.

[2] "The natural compound silvestrol is a potent inhibitor of Ebola virus replication". Antiviral Research 137: 76–81. January 2017. doi:10.1016/j.antiviral.2016.11.011. PMID 27864075.

[3] "Inhibition of Zika Virus Replication by Silvestrol". Viruses 10 (4): 149. March 2018. doi:10.3390/v10040149. PMID 29584632.

[4] "Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses". Antiviral Research 150: 123–129. February 2018. doi:10.1016/j.antiviral.2017.12.010. PMID 29258862.

[5] "Silvestrol Inhibits Chikungunya Virus Replication". Viruses 10 (11): 592. October 2018. doi:10.3390/v10110592. PMID 30380742.

[pmid32006468-6] "Recent discovery and development of inhibitors targeting coronaviruses". Drug Discovery Today 25 (4): 668–688. April 2020. doi:10.1016/j.drudis.2020.01.015. PMID 32006468.

[7] "Therapeutic potential of the translation inhibitor silvestrol in hepatocellular cancer". PLOS ONE 8 (9): e76136. 2013. doi:10.1371/journal.pone.0076136. PMID 24086701. Bibcode: 2013PLoSO...876136K.

[8] "Targeting the eIF4F translation initiation complex: a critical nexus for cancer development". Cancer Research 75 (2): 250–63. January 2015. doi:10.1158/0008-5472.CAN-14-2789. PMID 25593033.

[9] "Total synthesis of (-)-episilvestrol and (-)-silvestrol". Angewandte Chemie 46 (41): 7835–8. 2007. doi:10.1002/anie.200702700. PMID 17823902.

[10] "Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (-) and the eIF4A-inhibitor Silvestrol". Antiviral Research 175: 104706. January 2020. doi:10.1016/j.antiviral.2020.104706. PMID 31931103.

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Silvestrol

Topic: Chemistry

Bioactivity

See also

References

Identifiers

IUPAC name 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	697235-38-4^Y
PubChem CID	11787114
ChemSpider	9961792
UNII	KK3Y3KN5BV
ChEBI	CHEBI:66484
ChEMBL	ChEMBL555196
Chemical and physical data
Formula	C₃₄H₃₈O₁₃
Molar mass	654.7 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES 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 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