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

Research output: Contribution to journalArticlepeer-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 languageEnglish
Pages (from-to)14614-14629
Number of pages16
JournalChemistry - A European Journal
Volume21
Issue number41
DOIs
Publication statusPublished - Oct 5 2015

Keywords

  • glycosides
  • inhibitors
  • sialic acids
  • sphingolipids

ASJC Scopus subject areas

  • Medicine(all)

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