Synthesis and chemical characterization of several perfluorinated sialic acid glycals and evaluation of their: In vitro antiviral activity against Newcastle disease virus

TY - JOUR

T1 - Synthesis and chemical characterization of several perfluorinated sialic acid glycals and evaluation of their

T2 - In vitro antiviral activity against Newcastle disease virus

AU - Rota, P.

AU - Papini, N.

AU - La Rocca, P.

AU - Montefiori, M.

AU - Cirillo, F.

AU - Piccoli, M.

AU - Scurati, R.

AU - Olsen, L.

AU - Allevi, P.

AU - Anastasia, L.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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-4α heptafluorobutyryl derivative almost completely inhibited NDV-induced syncytium formation.

AB - 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-4α heptafluorobutyryl derivative almost completely inhibited NDV-induced syncytium formation.

U2 - 10.1039/c7md00072c

DO - 10.1039/c7md00072c

M3 - Journal article

C2 - 30108862

AN - SCOPUS:85025069138

SN - 2040-2503

VL - 8

SP - 1505

EP - 1513

JO - MedChemComm

JF - MedChemComm

IS - 7

ER -