The metabolism of formycin B in Leishmaniadonovani
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Add time:08/30/2019 Source:sciencedirect.com
Formycin B, a pyrazolo(4,3-d)pyrimidine C-nucleoside, inhibited the growth of Leishmaniadonovani promastigotes in culture with an ED90 of 0.2 μg/ml. Promastigotes incubated for 24 hrs with Formycin B at 10 μg/ml were found to convert it to the ribonucleotide, formycin B 5′-monophosphate. The parasites were also capable of aminating formycin B 5′-monophosphate as evidenced by the appearance of formycin A di- and triphosphate. The RNA contained the formycin A moiety in 3′,5′-polynucleotide linkage. Succino-AMP synthetase from these parasites was able to use formycin B 5′-monophosphate as an alternate-substrate with a K'm of 26 μM and a V'm of about 1% the V'm IMP. Formycin B 5′-monophosphate was also a substrate for mammalian succino-AMP synthetase with a Vm' of 40% the Vm' of IMP.
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