bromodeoxycytidine and Sarcoma-180

The 5'-hydroxymethylene function of several uracil and cytosine nucleosides has been modified to produce a variety of uronic acids, uronates, uronamides, and urononitriles of 2'-deoxy-beta-D-erythro-pentofuranosyl- and beta-D-arabino-pentofuranosylpyrimidines. In addition, the 5 position in many of these nucleosides has been substituted by a halogen atom. Twenty-one of the 35 compounds synthesized and examined for biological activity have not been previously reported. The purity of the products was measured by a high-pressure liquid chromatographic method. They were then evaluated as potential growth inhibitors of murine Sarcoma 180 cells in culture, of herpes simplex virus type 1 in vitro, and of Streptococcus faecium, a folic acid or deoxythymidine dependent bacterial strain. The ability of these nucleoside analogues to inhibit the phosphorylation of deoxythymidine by herpes simplex virus type 1 encoded pyrimidine deoxyribonucleoside kinase was also investigated and a structure-activity relationship examined.

Topics: Animals; Cell Division; Cells, Cultured; Chick Embryo; Pyrimidine Nucleosides; Sarcoma 180; Simplexvirus; Streptococcus; Structure-Activity Relationship; Substrate Specificity; Thymidine Kinase; Thymidylate Synthase; Uronic Acids; Virus Replication