Feedback inhibition of purine biosynthesis in ascites tumor cells by purine analogues

Abstract

The ability of 37 purine analogues to inhibit purine biosynthesis de novo in Ehrlich ascites tumor cells in vitro has been examined in an attempt to define structural requirements for this reaction. Only 8 analogues were active feedback inhibitors. 6-Methylthiopurine ribonucleoside was more active than adenine, while 6-methylpurine was as active as adenine. 2,6-Diaminopurine, 6-benzylthiopurine, psicofuranine, 2-amino-6-benzylthiopurine, purine, and thioguanine ribonucleoside were approximately as active as the less active natural purines. No compound tested interfered with feedback inhibition by adenine. Combinations of adenine with purine or 2,6-diaminopurine, or of purine with diaminopurine, inhibited in a potentiative manner. No correlation was observed between feedback inhibitory activity and nucleotide formation by purine analogues.