Synthesis and biological evaluation of several dephosphonated analogues of CMP-Neu5Ac as inhibitors of GM3-synthase

Paola Rota; Federica Cirillo; Marco Piccoli; Antonio Gregorio; Guido Tettamanti; Pietro Allevi; Luigi Anastasia

doi:10.1002/chem.201501770

Synthesis and biological evaluation of several dephosphonated analogues of CMP-Neu5Ac as inhibitors of GM3-synthase

Paola Rota, Federica Cirillo, Marco Piccoli, Antonio Gregorio, Guido Tettamanti, Pietro Allevi, Luigi Anastasia

IRCCS Policlinico San Donato

Research output: Contribution to journal › Article › peer-review

Abstract

Previous studies demonstrated that reducing the GM3 content in myoblasts increased the cell resistance to hypoxic stress, suggesting that a pharmacological inhibition of the GM3 synthesis could be instrumental for the development of new treatments for ischemic diseases. Herein, the synthesis of several dephosphonated CMP-Neu5Ac congeners and their anti-GM3-synthase activity is reported. Biological activity testes revealed that some inhibitors almost completely blocked the GM3-synthase activity in vitro and reduced the GM3 content in living embryonic kidney 293A cells, eventually activating the epidermal growth factor receptor (EGFR) signaling cascade.

Original language	English
Pages (from-to)	14614-14629
Number of pages	16
Journal	Chemistry - A European Journal
Volume	21
Issue number	41
DOIs	https://doi.org/10.1002/chem.201501770
Publication status	Published - Oct 5 2015

Keywords

glycosides
inhibitors
sialic acids
sphingolipids

ASJC Scopus subject areas

Medicine(all)

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10.1002/chem.201501770

Cite this

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abstract = "Previous studies demonstrated that reducing the GM3 content in myoblasts increased the cell resistance to hypoxic stress, suggesting that a pharmacological inhibition of the GM3 synthesis could be instrumental for the development of new treatments for ischemic diseases. Herein, the synthesis of several dephosphonated CMP-Neu5Ac congeners and their anti-GM3-synthase activity is reported. Biological activity testes revealed that some inhibitors almost completely blocked the GM3-synthase activity in vitro and reduced the GM3 content in living embryonic kidney 293A cells, eventually activating the epidermal growth factor receptor (EGFR) signaling cascade. ",

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AU - Rota, Paola

AU - Cirillo, Federica

AU - Piccoli, Marco

AU - Gregorio, Antonio

AU - Tettamanti, Guido

AU - Allevi, Pietro

AU - Anastasia, Luigi

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AB - Previous studies demonstrated that reducing the GM3 content in myoblasts increased the cell resistance to hypoxic stress, suggesting that a pharmacological inhibition of the GM3 synthesis could be instrumental for the development of new treatments for ischemic diseases. Herein, the synthesis of several dephosphonated CMP-Neu5Ac congeners and their anti-GM3-synthase activity is reported. Biological activity testes revealed that some inhibitors almost completely blocked the GM3-synthase activity in vitro and reduced the GM3 content in living embryonic kidney 293A cells, eventually activating the epidermal growth factor receptor (EGFR) signaling cascade.

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Synthesis and biological evaluation of several dephosphonated analogues of CMP-Neu5Ac as inhibitors of GM3-synthase

Abstract

Keywords

ASJC Scopus subject areas

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