In vitro metabolism of 1-beta-D-arabinofuranosylcytosine and 1-beta-2'-fluoroarabino-5-iodocytosine in normal and herpes simplex type 1 virus-infected cells

Biochemical Pharmacology
W KreisC Lopez

Abstract

Phosphorylation of 1-beta-D-2'-F-arabino-5-iodocytosine (FIAC), a newly synthesized pyrimidine nucleoside with potent antiherpesvirus activity, was compared with that of its parent compound, 1-beta-D-arabinofuranosylcytosine (ara-C). While ara-C was phosphorylated extensively by homogenates of normal, rapidly proliferating mouse tissues, FIAC was a poor substrate for the nucleoside kinase occurring in such normal tissues. With cell homogenates of noninfected Vero cells, thymidine (TdR) was phosphorylated about fifty and twenty times more efficiently than FIAC and ara-C, while infection of Vero cells with Herpes Simplex Virus Type 1 (HSV-1) resulted in a 23-fold increase of TdR- and a 1270-fold increase of FIAC phosphorylation. In contrast, phosphorylation of ara-C was increased only by a factor of 2.6. While the reaction products obtained with homogenates of normal mouse tissues were 5'-mono-, di- and triphosphates of ara-C and FIAC, the reaction products with noninfected and infected Vero cell homogenates were predominantly monophosphates. In contrast, TdR was efficiently phosphorylated to its 5'-mono-, di- and triphosphates by such homogenates. In intact HSV-1-infected Vero cells. FIAC was rapidly taken up and phosphorylated ...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·G B ElionH J Schaeffer
May 1, 1980·Antimicrobial Agents and Chemotherapy·C LopezJ J Fox
Jan 1, 1964·Proceedings of the Society for Experimental Biology and Medicine·D A BUTHALA
Nov 1, 1974·Antimicrobial Agents and Chemotherapy·C B LauterA M Lerner

Citations

Jan 6, 1999·Archives of Pharmacal Research·J H HongC K Chu
Jan 1, 1985·Advances in Enzyme Regulation·G B Elion
Oct 1, 1983·Antimicrobial Agents and Chemotherapy·J M Colacino, C Lopez

Related Concepts

Fiacitabine, (alpha-D)-isomer
Antiviral Agents
Cytonal
Herpes Simplex Infections
Phosphorylation
Thymidine
In Vitro [Publication Type]

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