Synthesis and chemical characterization of several perfluorinated sialic acid glycals and evaluation of their in vitro antiviral activity against Newcastle disease virus
| Autor: | Pietro Allevi, Marco Piccoli, Federica Cirillo, Paola Rota, Luigi Anastasia, Marco Montefiori, Raffaele Scurati, P. La Rocca, Nadia Papini, Lars Folke Olsen |
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| Přispěvatelé: | Rota, P., Papini, N., La Rocca, P., Montefiori, M., Cirillo, F., Piccoli, M., Scurati, R., Olsen, L., Allevi, P., Anastasia, L. |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
fusion binding Paramyxoviridae receptor Pharmaceutical Science Biochemistry Newcastle disease Virus 03 medical and health sciences chemistry.chemical_compound 3-didehydro-N-acetylneuraminic acid cladosiphon-okamuranu host-cell medicinal chemistry Drug Discovery Pharmacology chemistry.chemical_classification Syncytium biology Chemistry accurate docking Organic Chemistry Hemagglutinin-neuraminidase inhibitor biology.organism_classification In vitro Sialic acid 030104 developmental biology 2-deoxy-2 Docking (molecular) Molecular Medicine protein Glycoprotein |
| Zdroj: | MedChemComm. 8:1505-1513 |
| ISSN: | 2040-2511 2040-2503 |
| DOI: | 10.1039/c7md00072c |
| Popis: | Newcastle Disease Virus (NDV), belonging to the Paramyxoviridae family, causes a serious infectious disease in birds, resulting in severe losses in the poultry industry every year. Haemagglutinin neuraminidase glycoprotein (HN) has been recognized as a key protein in the viral infection mechanism, and its inhibition represents an attractive target for the development of new drugs based on sialic acid glycals, with the 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (Neu5Ac2en) as their backbone. Herein we report the synthesis of several Neu5Ac2en glycals and of their perfluorinated C-5 modified derivatives, including their respective stereoisomers at C-4, together with evaluation of their in vitro antiviral activity. While all synthesized compounds were found to be active HN inhibitors in the micromolar range, we found that their potency was influenced by the chain-length of the C-5 perfluorinated acetamido functionality. Thus, the binding modes of the inhibitors were also investigated by performing a docking study. Moreover, the perfluorinated glycals were found to be more active than the corresponding normal C-5 acylic derivatives. Finally, cell-cell fusion assays on NDV infected cells revealed that the addition of a newly synthesized C-4 alpha heptafluorobutyryl derivative almost completely inhibited NDV-induced syncytium formation. |
| Databáze: | OpenAIRE |
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