Figure 5

Biochemical effect of the bisthiazoliums T4. A- Effect of T4 on the biosynthesis of phospholipids and nucleic acids. P. falciparum trophozoite-infected erythrocytes were incubated in the presence of the indicated concentrations of T4 at time 0 and radioactive choline (5 μM), ethanolamine (2 μM) and hypoxanthine were added at time 30 min. Incorporation of the radioactive precursors into their corresponding macromolecules at time 4 h are expressed as percentage of those measured in infected erythrocytes incubated without T4 and are means of 4 experiments ± SEM. In the absence of drugs, choline incorporation into PC was 4.71 ± 0.26 nmol/10¹⁰ cells/hour, and ethanolamine incorporation into phosphatidylethanolamine PE and into PC (indicated as PC*) was 14.3 ± 0.33 and 1.97 ± 0.16 nmol/10¹⁰ cells/hour. Effects of T4 on choline (B) and ethanolamine (C) water-soluble metabolites. P. falciparum-infected erythrocytes were incubated in the presence of the indicated concentrations of T4 at time 0. Radioactive choline (20 uM) and ethanolamine (2 uM) were added at time 30 min and reactions were stopped at time 2.5 hours. Incorporation of the radioactive precursors into their corresponding metabolites is expressed as percentage of those measures in infected cells incubated without T4 and are means of 4 experiments ± SEM. In the absence of drugs, intracellular choline, phosphocholine and CDP-choline were respectively 1.1 ± 0.1, 23.7 ± 0.5 and 0.30 ± 0.01 nmol/10¹⁰ cells/hour. In C, phosphorylethanolamine and phosphocholine and the sum CDP-choline + CDP ethanolamine were respectively 4.90 ± 0.25 and 1.86 ± 0.07 and 0.77 ± 0.06 nmol/10¹⁰ cells/hour. Incorporation of Eth into P-ETn is not affected by T4.