Antagonists of Growth Inhibition of Crithidia by Allopurinol, a Guanine Analog

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Abstract
SYNOPSIS. Allopurinol, 4‐hydroxypyrazolo[3,4‐d] pyrimidine, a relatively non‐toxic xanthine‐oxidase inhibitor used to treat gout, inhibited growth (ID0–90 1.0 μg/ml) of the trypanosomatid flagellate of insects Crithidia fasciculata in minimal media in respect to biopterin, folic acid and purine. Allopurinol inhibition was antagonized by thymidine (4.0 μg/ml) when a) biopterin (≥ 1.0 ng) was present alone; traces of folate entering from the inoculum or contamination of chemicals probably sufficed here to satisfy the folate requirement; b) biopterin (5% pure) 1.0 ng was added together with either pteroylglutamic acid (PGA) 4.0 ng or hypoxanthine 0.01 mg. With biopterin absent, full growth was permitted by PGA 10 ng + hypoxanthine 0.03 mg, and completely inhibited by the standard concentration of allopurinol, but in this instance thymidine did not release the inhibition.Allopurinol is therefore useful for investigating pteridine function via inhibition analysis with the singularity that folate acts uniquely in trypanosomatids as precursor of biopterin, and the complication that both pteridines catalyze multiple biosyntheses. The biosynthetic step between folate and biopterin is postulated to be a site of inhibition of allopurinol in Crithidia.