(1R,2R,3S,3aR,8bS)-6-[[(2S,3R,6R)-6-[(1R)-1,2-Dihydroxyethyl]-3-methoxy-1,4-dioxan-2-yl]oxy]-2,3,3a,8b-tetrahydro-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-1H-cyclopenta[b]benzofuran-2-carboxylic acid methyl ester Chemical Properties

Melting point:

120-122℃

Boiling point:

800.8±65.0 °C(Predicted)

Density 

1.45

storage temp. 

Store at -20°C

solubility 

Soluble in DMSO

form 

Powder

pka

11.57±0.70(Predicted)

color 

White to off-white

(1R,2R,3S,3aR,8bS)-6-[[(2S,3R,6R)-6-[(1R)-1,2-Dihydroxyethyl]-3-methoxy-1,4-dioxan-2-yl]oxy]-2,3,3a,8b-tetrahydro-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-1H-cyclopenta[b]benzofuran-2-carboxylic acid methyl ester Usage And Synthesis

Uses

Silvestrol is a eukaryotic translation initiation factor 4A (eIF4A) inhibitor isolated from Agave americana Linn.. Silvestrol induces autophagy and caspase-mediated apoptosis[1][2][3].

Definition

ChEBI: An organic heterotricyclic compound that consists of a 2,3,3a,8b-tetrahydro-H-benzo[b]cyclopenta[d]furan framework substituted by hydroxy groups at positions C-1 and C-8b, a methoxycarbonyl group at C-2, a phen l group at C-3, a 4-methoxyphenyl group at C-3a, a methoxy group at C-8 and a 1,4-dioxan-2-yloxy group at position C-6 which in turn is substituted by a methoxy group at position 3 and a 1,2-dihydroxyethyl group at position 6. Isolated from Aglaia si vestris, it exhibits antineoplastic activity.

Anticancer Research

It is a natural flavogline compound from the group of cyclopenta[b]benzofurans,extracted from the fruits of Aglaila sylvestre, which shows anticancer activityagainst lung and breast cancers (Shoeb 2006). The plant extract is reported to bepotent against P-388 cells in in vivo experiments. In the hollow fiber in vivo assay,it shows cytotoxicity in a dose-dependent way. It works by altering the cell signal pathways that related to the cell survival as well as angiogenesis and exerts itseffects by inhibiting the translation of mRNA preferentially associated withmalignancy (Balunas and Kinghorn 2005; Cencic et al. 2009).

in vivo

IC 50

eIF4

References

[1] Chambers JM, et al. Synthesis of biotinylated episilvestrol: highly selective targeting of the translation factors eIF4AI/II. Org Lett. 2013 Mar 15;15(6):1406-9. DOI:10.1021/ol400401d
[2] Kim S, et al. Silvestrol, a potential anticancer rocaglate derivative from Aglaia foveolata, induces apoptosis in LNCaP cells through the mitochondrial/apoptosome pathway without activation of executioner caspase-3 or -7. Anticancer Res. 2007 Jul-Aug;27(4B):2175-83. PMID:17695501
[3] Chen WL, et al. Silvestrol induces early autophagy and apoptosis in human melanoma cells. BMC Cancer. 2016 Jan 13;16:17. DOI:10.1186/s12885-015-1988-0
[4] Daker M, et al. Inhibition of nasopharyngeal carcinoma cell proliferation and synergism of CDDP with silvestrol and episilvestrol isolated from Aglaia stellatopilosa. Exp Ther Med. 2016 Jun;11(6):2117-2126. DOI:10.3892/etm.2016.3201
[5] Patton JT, et al. The translation inhibitor silvestrol exhibits direct anti-tumor activity while preserving innate and adaptive immunity against EBV-driven lymphoproliferative disease. Oncotarget. 2015 Feb 20;6(5):2693-708. DOI:10.18632/oncotarget.2098
[6] Wolfe AL, et al. RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer. Nature. 2014 Sep 4;513(7516):65-70. DOI:10.1038/nature13485
[7] Wiegering A, et al. Targeting Translation Initiation Bypasses Signaling Crosstalk Mechanisms That Maintain High MYC Levels in Colorectal Cancer. Cancer Discov. 2015 Jul;5(7):768-781. DOI:10.1158/2159-8290.CD-14-1040
[8] Todt D, et al. The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo. Antiviral Res. 2018 Sep;157:151-158. DOI:10.1016/j.antiviral.2018.07.010

(1R,2R,3S,3aR,8bS)-6-[[(2S,3R,6R)-6-[(1R)-1,2-Dihydroxyethyl]-3-methoxy-1,4-dioxan-2-yl]oxy]-2,3,3a,8b-tetrahydro-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-1H-cyclopenta[b]benzofuran-2-carboxylic acid methyl ester(697235-38-4)Related Product Information

• N,N-DIETHYLBENZAMIDE