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.
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, Institution University of Milan, Via Saldini 50, 20133 Milan (Italy).
authors.forename: Paola
authors.initials: P
authors.lastname: Rota
authors.affiliation: Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan (Italy).
authors.forename: Federica
authors.initials: F
authors.lastname: Cirillo
authors.affiliation: Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan (Italy).
authors.forename: Marco
authors.initials: M
authors.lastname: Piccoli
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, Institution University of Milan, Via Saldini 50, 20133 Milan (Italy).
authors.forename: Antonio
authors.initials: A
authors.lastname: Gregorio
authors.affiliation: Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan (Italy).
authors.forename: Guido
authors.initials: G
authors.lastname: Tettamanti
authors.affiliation: Department of Biomedical, Surgical and Dental Sciences, Institution University of Milan, Via Saldini 50, 20133 Milan (Italy).
authors.forename: Pietro
authors.initials: P
authors.lastname: Allevi
authors.affiliation: Department of Biomedical Sciences for Health, Institution University of Milan, Segrate Milan (Italy). luigi.anastasia@unimi.it.|Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan (Italy). luigi.anastasia@unimi.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Anastasia
mesh_terms: D003568:Cytidine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D066246:ErbB Receptors / Q000737:chemistry*; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000201:enzymology*; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D012799:Sialyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D012794:Sialic Acids; C561601:cytidine-5'-monophosphosialic acid; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D012799:Sialyltransferases; C021343:haematoside synthetase; D066246:ErbB Receptors; D003568:Cytidine Monophosphate
keywords: glycosides; inhibitors; sialic acids; sphingolipids