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.[1]References
- Metabolism and mechanism of action of formycin B in Leishmania. Rainey, P., Santi, D.V. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
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