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 journalArticle

7 Citations (Scopus)

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

Fingerprint

Myoblasts
Bioactivity
Epidermal Growth Factor Receptor
Testis
Pharmacology
Kidney
haematoside synthetase
cytidine-5'-monophosphosialic acid
In Vitro Techniques
Epidermal Growth Factor

Keywords

  • glycosides
  • inhibitors
  • sialic acids
  • sphingolipids

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Synthesis and biological evaluation of several dephosphonated analogues of CMP-Neu5Ac as inhibitors of GM3-synthase. / Rota, Paola; Cirillo, Federica; Piccoli, Marco; Gregorio, Antonio; Tettamanti, Guido; Allevi, Pietro; Anastasia, Luigi.

In: Chemistry - A European Journal, Vol. 21, No. 41, 05.10.2015, p. 14614-14629.

Research output: Contribution to journalArticle

@article{fe525dffa3cb43ae897613c69e23232b,
title = "Synthesis and biological evaluation of several dephosphonated analogues of CMP-Neu5Ac as inhibitors of GM3-synthase",
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.",
keywords = "glycosides, inhibitors, sialic acids, sphingolipids",
author = "Paola Rota and Federica Cirillo and Marco Piccoli and Antonio Gregorio and Guido Tettamanti and Pietro Allevi and Luigi Anastasia",
year = "2015",
month = "10",
day = "5",
doi = "10.1002/chem.201501770",
language = "English",
volume = "21",
pages = "14614--14629",
journal = "Chemistry - A European Journal",
issn = "0947-6539",
publisher = "Wiley-VCH Verlag",
number = "41",

}

TY - JOUR

T1 - Synthesis and biological evaluation of several dephosphonated analogues of CMP-Neu5Ac as inhibitors of GM3-synthase

AU - Rota, Paola

AU - Cirillo, Federica

AU - Piccoli, Marco

AU - Gregorio, Antonio

AU - Tettamanti, Guido

AU - Allevi, Pietro

AU - Anastasia, Luigi

PY - 2015/10/5

Y1 - 2015/10/5

N2 - 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.

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.

KW - glycosides

KW - inhibitors

KW - sialic acids

KW - sphingolipids

UR - http://www.scopus.com/inward/record.url?scp=84973410066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973410066&partnerID=8YFLogxK

U2 - 10.1002/chem.201501770

DO - 10.1002/chem.201501770

M3 - Article

VL - 21

SP - 14614

EP - 14629

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

IS - 41

ER -