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.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
MeSH terms
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Cytidine Monophosphate / analogs & derivatives*
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Cytidine Monophosphate / chemical synthesis
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Cytidine Monophosphate / chemistry
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Cytidine Monophosphate N-Acetylneuraminic Acid / chemistry*
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Cytidine Monophosphate N-Acetylneuraminic Acid / metabolism
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry*
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ErbB Receptors / chemistry*
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Humans
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Kidney / chemistry
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Kidney / enzymology*
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Sialic Acids / chemical synthesis*
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Sialic Acids / chemistry*
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Sialyltransferases / antagonists & inhibitors*
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Sialyltransferases / chemistry*
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Sialyltransferases / metabolism
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Signal Transduction / drug effects
Substances
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Enzyme Inhibitors
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Sialic Acids
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cytidine-5'-monophosphosialic acid
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Cytidine Monophosphate N-Acetylneuraminic Acid
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Sialyltransferases
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haematoside synthetase
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ErbB Receptors
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Cytidine Monophosphate