Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/930505

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Title
Synthesis and biological activity of Δ-5,6-norcantharimides: importance of the 5,6-bridge
Author/Creator
Thaqi, Ali;  Scott, Janet L.;  Gilbert, Jayne;  Sakoff, Jennette A.;  McCluskey, Adam
Institution
The University of Newcastle. Faculty of Science & Information Technology, School of Environmental and Life Sciences
Description
Cantharidin (1) and norcantharidin (2) are potent protein phosphatase 1 and 2A inhibitors that also display high levels of anticancer activity against a broad range of tumor cells lines. Surprisingly, Δ-5,6-ethyl norcantharidin (3, cis-tetrahydrofurano[3,4-c]furan-1,3-dione) displays neither phosphatase inhibition nor anticancer activity. This suggests that the 5,6-ethyl bridge is pivotal to both anti-cancer and protein phosphatase activity. Additionally bioisosteric replacement of the ethereal oxygen has no effect on biological activity nor does modification of the anhydride moiety. Unlike the parent norcantharidin, anhydride ring opening has no effect on either protein phosphatase inhibition or anti-cancer activity. Additionally, this work highlights the discovery of the octyl substituted, cis-5-benzyl-2-hexyltetrahydro-2H,3aH-pyrrolo[3,4-c]pyrrole-1,3-dione, 9p, and the octyl substituted, cis-octyltetrahydro-5H-furo[3,4-c]pyrrole-4,6-dione, 8p, as two new cytotoxic agents which are equipotent (9p) with, and more potent (8p) than norcantharidin.
Relation
European Journal of Medicinal Chemistry Vol. 45, Issue 5, p. 1717-1723
Publisher Link
http://dx.doi.org/10.1016/j.ejmech.2010.01.004
Date
2010
Publisher
Elsevier
Keyword(s)
cantharidin;  norcantharidin;  Δ-5,6-ethyl bridge;  anti-cancer;  protein phosphatase 1 & 2A
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/930505
Identifier
ISSN:0223-5234
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Subject
"European Journal of Medicinal Chemistry"
 
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