Metabolism and mechanism of action of formycin B in Leishmania.
Formycin B is a potent inhibitor of growth of the promastigote forms of Leishmania tropica, L. mexicana, L. braziliensis, and L. donovani. The metabolic products formed in these organisms are formycin B 5'-monophosphate and formycin A 5'-mono-, di-, and triphosphates, with formycin A 5'-triphosphate predominating. In addition, formycin A is extensively incorporated into RNA. From the metabolic profile, we conclude that formycin B is first converted to the 5'-monophosphate by the nucleoside phosphotransferase found in Leishmania and is subsequently converted to cytotoxic adenosine nucleotide analogs of formycin A that become incorporated into RNA. The metabolism and mechanism of formycin B appears to be qualitatively similar to that of allopurinol riboside, but quantitative differences and species selectivity suggest that these agents may have a different spectrum of activity as potential anti-leishmanial agents.
D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D005573:Formycins / Q000378:metabolism* / Q000627:therapeutic use; D007891:Leishmania / Q000254:growth & development / Q000378:metabolism*; D007896:Leishmaniasis / Q000188:drug therapy; D012265:Ribonucleotides / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D005573:Formycins; D012265:Ribonucleotides