Metabolism and mechanism of action of formycin B in Leishmania.

Abstract

Formycin B is a potent inhibitor of growth of the promastigote forms of L. tropica, L. mexicana, L. braziliensis and L. donovani [mammalian parasite]. The metabolic products formed in these organisms are formycin B 5''-monophosphate anbd formycin A 5''-mono-, di- and triphosphates, with formycin A 5''-triphosphate predominating. Formycin A is extensively incorporated into RNA. From the metabolic profile, it was concluded 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.