Effects of fluorinated inositols on the phosphoinositide metabolism and the proliferation of Trypanosoma cruzi

Inositol has been cited as being essential for the growth of micro-organism s and animals. Its action rests mostly in the formation of a set of inosito l-containing lipids, including phosphatidylinositol and its phosphorylated derivatives. To evaluate the functional responses coupled to the phosphoino sitide metabolism in Trypanosoma cruzi we used myo-inositol and its six flu orinated analogues. Their uptake into epimastigotes \yas characterised usin g tritium-labeled myo-inositol and monodeoxyfluoro-myo-inositols. The analo gues were tested for their ability to inhibit [H-3]-myo-inositol incorporat ion into phosphoinositides and the proliferation of epimastigotes and amast igotes. The results showed differences between T. cruzi and mammalian syste ms in the responses to the fluorinated analogues. We found that the 3-, 5- and 6-fluoro analogues did not enter the cells but had an inhibitory effect on the incorporation of the radioactive inositol into lipids and on the am astigotes' and epimastigotes' replication. The most effective inhibitor, 1- D-6-deoxy-6-myo-inositol, had no effect on mammalian cell division.