Metabolism of formycin B by Leishmania amastigotes in vitro. Comparative metabolism in infected and uninfected human macrophages.
Formycin B is metabolized by cutaneous Leishmania amastigotes within cultured human macrophages to give formycin B 5'-monophosphate and formycin A 5'-mono-, di-, and triphosphates. Formycin A is also incorporated into RNA. The activity of formycin B against amastigotes was correlated with the levels of formycin A metabolites formed in the parasites. Uninfected macrophages also convert formycin B into the same products, but the levels are markedly lower than those seen in infected macrophages. The results suggest that a sufficient therapeutic index exists to warrant consideration of formycin B as an anti-leishmanial drug in humans.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D002478:Cells, Cultured; D005573:Formycins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007891:Leishmania / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D005573:Formycins; C034561:formycin B; D012313:RNA