Synthesis and Biological Evaluation of Several Dephosphonated Analogues of CMP‐Neu5Ac as Inhibitors of GM3‐Synthase |
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| Authors: | Dr. Paola Rota Dr. Federica Cirillo Dr. Marco Piccoli Dr. Antonio Gregorio Prof. Guido Tettamanti Prof. Pietro Allevi Prof. Luigi Anastasia |
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| Affiliation: | 1. Department of Biomedical, Surgical and Dental Sciences, Institution University of Milan, Via Saldini 50, 20133 Milan (Italy);2. Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan (Italy);3. Department of Biomedical Sciences for Health, Institution University of Milan, Segrate Milan (Italy) |
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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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| Keywords: | glycosides inhibitors sialic acids sphingolipids |
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