SUMMARYWe have previously shown the presence of various purine salvage enzymes in Trypanosoma cruzi, including phosphoribosyltransferase, aminohydrolase, kinase, phosphorylase and hydrolase activities. We now report that a similar situation occurs in Leishmania mexicana amazonensis and Trypanosoma brucei brucei. In all three organisms we found higher levels of activity for the phosphoribosyltransferase enzymes than for the nucleoside kinases, suggesting a preference for the salvage of purine bases rather than nucleosides. Similarly, absence of inosine phosphorylase activity suggests that only one route for the salvage of hypoxanthine is available to the three organisms. The most striking difference was that whereas T. cruzi and T. brucei possessed adenosine aminohydrolase activity, this was not detected in L. mexicana; instead adenine amino-hydrolase activity was found. The overall similarity, as judged by the distribution of enzyme activities, of purine salvage in these three members of the kinetoplastida suggest a broad spectrum of activity for any inhibitor acting in this area; the plethora of alternative salvage pathways, however, suggests that in no case would such inhibition be cidal.
Nitazoxanide, tizoxanide and a new analogue [4-nitro-N-(5-nitro-1,3-thiazol-2-yl)benzamide; NTB] inhibit the growth of kinetoplastid parasites (Trypanosoma cruzi and Leishmania mexicana) in vitro