In search for effective inhibitors of sugar processing enzymes the uridine derivatives of (5-amino-2-pyridyl) 1-thioglycosides attract our attention as substrate analogs. Along this line, we have reported different methodology for the synthesis of compounds in which heteroaryl 1-thioglycosides derivatives of D-glucose and D-galactose were connected to selectively protected uridine by amide bond. As a spacer between these two parts we have chosen a succinic acid. In order to obtain uridine with ester bond connected succinic acid in good yield we applied microwave irradiation. The construction of amide bonds was performed using DCC/DMAP [1], ethyl chloroformate [2] or DMTMM as condensing agent [3]. This way we obtained uridine derivatives GP-U1, GP-U2 and GP-U3 and then we tested their biological activity.

The three inhibitors tested by us exhibited relatively low toxic effect on cells in in vitro tests using swine kidney (SK6) cells. High antiviral activity against classical swine fever virus (CSFV) was demonstrated by inhibiting the propagation of the virus. We have investigated the formation of envelope glycoproteins of CSFV after inhibitor treatment by immunoperoxidase monolayer assay and by immunoblotting. We showed that they can influence, not only glycosylation, but also the stability of E2 protein, effectively inhibiting the formation of glycoprotein complexes.

Acknowledgement

Financial support from the Polish State Committee for Scientific Research (Grant No. 1 T09A 08630) is gratefully acknowledged.

[1] Butterworth J.; Moran J. et. al.J. Med. Chem. 1987, 30, 8, 1295-1302
[2] Chaudhary A.; Girgis M.; Prashad M.et. al. Tetrahedron Lett. 2003, 44, 5543-5546
[3] Kunishima, M.; Kawachi, C. et. al. Tetrahedron 2001, 57, 1551-1558

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