Nucleoside analogs as non-substrate inhibitors of herpes simplex viruses thymidine kinase.
We have examined the capacity of a series of 6-substituted pyrimidine and 2-substituted purine derivatives to inhibit mammalian thymidine kinase and the thymidine kinases encoded by type 1 and type 2 herpes simplex viruses. Several N2-substituted guanine and deoxy guanosine derivatives displayed selective inhibitory activity against the HSV-1 and HSV-2 thymidine kinases by competing with the phosphorylation of thymidine, suggesting a possible novel pharmacological approach to herpes viruses infections.
Focher
F
F
Istituto di Genetica Biochimica ed Evoluzionistica, CNR, Pavia, Italy.
Sandoli
D
D
Hildebrand
C
C
Sangalli
S
S
Ciarrocchi
G
G
Rebuzzini
A
A
Pedrali-Noy
G
G
Manservigi
R
R
Wright
G
G
Brown
N
N
D002478:Cells, Cultured; D006367:HeLa Cells; D007700:Kinetics; D009705:Nucleosides / Q000494:pharmacology*; D018139:Simplexvirus / Q000201:enzymology*; D013936:Thymidine / Q000378:metabolism; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors*
D009705:Nucleosides; D013937:Thymidine Kinase; D013936:Thymidine