Inhibitory action of the adenine analog, 4-aminopyrazolo(3,4-d)pyrimidine, in Crithidia fasciculata

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Abstract
The adenine analog 4-aminopyrazolo(3,4-d)pyrimidine inhibits the growth of the kinetoplastic (trypanosomatid) flagellate C. fasciculata. This inhibition is partially overcome only by adenine (of a number of purines tested), with an inhibition index of 0.025. More effective reversal of inhibition is obtained with any of a number of naturally occurring pyrimidine compounds, up to a concentration of 0.18 mM. Higher concentrations of pyrimidines or addition of guanine, as well as adenine and uracil to the medium increases inhibition. The analog (presumably as the ribonucleoprotide) was inhibitory to any enzyme of the pyrimidine biosynthetic pathway that could be tested. It probably competed with adenine for adenine phosphoribosyltransferase (AMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.7), was converted to a ribonucleotide, and was incorporated into nucleic acid.