6-Azauridine, an Inhibitor of the Purine Salvage Pathway

Abstract

Since the time when the knowledge about nucleic acid metabolism has been extended and the connection to malignant processes was recognized efforts were made to find new inhibitors interfering with different stages of nucleic acid metabolism. One of the pathways involved in these processes is the purine salvage pathway. Henderson (1) and Lau (2) examined different purine and pyrimidine derivatives and analogues for their ability to inhibit the enzymes of the purine-phosphoribosyltransferase. Henderson (1) found 13 compounds out of 116 chemicals which showed more than 75% inhibition of the adenine-phosphoribosyltransferase. Most of them were adenine analogues. Lau (2) on the other hand, investigated different purine and pyrimidine derivatives to inhibit the hypoxanthine- guanine-phosphoribosyltransferase activity of human erythrocytes. There were only some purine and purine nucleoside analogues active inhibitors of these enzymes. Similar experiments were reported by Lau (3) of Ehrlich ascites tumor cells.