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A variety of oxypurines and 6-thiopurines could be transformed by intact erythrocytes to their nucleoside triphosphate forms when incubations were extended for up to 24 hrs. The specific nucleotide monophosphate kinases which accomplish these reactions in erythrocytes were not identified but their ability to utilize 6-thioIMP, 6-thioXMP and 6-methylthioGMP as substrates, albeit very slowly, is clearly implied by these results. S-methylation of 6-thiopurines was demonstrated in erythrocytes incubated with physiological amounts of methionine-(CH3-3H). 6-Methylthioguanosine triphosphate and 6-methylmercaptopurine riboside triphosphate were formed in micromolar amounts, probably from the corresponding thiopurine nucleotides by methyl transfer from S-adenosylmethionine.

HPP-Rib is a potent antileishmanial agent, which has been useful in defining new and unusual purine metabolizing pathways in leishmaniae, in comparison with those in the host. The ribosyl linkage both in the parasite and in the host is resistant to cleavage. In the parasite there is a selective and marked conversion of HPP-Rib to HPP-Rib-5'-P and 4-APP ribonucleotides as well as incorporation into RNA, which does not occur in the host. These findings with HPP-Rib suggest a new chemotherapeutic approach which may be exploited in the treatment of leishmaniasis.

In animals and in humans given high doses of allopurinol, the oxidation of allopurinol to oxipurinol is inhibited, resulting in a higher proportion of unchanged allopurinol and of allopurinol riboside in plasma and urine than is seen at low doses. The dose which produces this inhibition of allopurinol oxidation is higher in rodents than in man or in the dog. Urinary orotate and orotidine increased in proportion to the dose of allopurinol. These increased levels of orotate would be expected to compete more effectively with 5-fluorouracil for conversion to a nucleotide by orotate phosphoribosyltransferase. Since allopurinol and allopurinol riboside are active against leishmaniae in vitro, it may be possible to attain therapeutic levels of allopurinol and allopurinol riboside in vivo by using high doses of allopurinol.