Antiplasmodial agents

For the determination of the antiplasmodial activity of the compounds, the multi-resistant Dd2 strain of Plasmodium falciparum was used and [8-3H]-hypoxanthine incorporated into the parasitic nucleic acids measured. The plasmodia were incubated with 0.3% parasitemia and an erythrocyte hematocrit of 2.5% in the presence of different concentrations of selected experimental agents in a final volume of 200 xl. The medium employed was RPMI 1640 containing 10% of heat-treated human serum and 3 mg/1 of gentamycin. In the incubations, the concentrations of the compounds varied from 0.3 to 100 xM. After 48 hours, each batch was treated with 50 xl [8-3H]hypoxanthine and incubated additional 18 hours. Testing results are provided in Table 1. 

We have defined the antiplasmodial selectivity index of a test substance in terms of mammalian KB cells. These cells were selected by precedent (123) and also because, in our experience, this line exhibits an intermediate sensitivity to a large number of cytotoxic agents when compared to cell lines derived from a variety of other human tumors. At the present time, we are not certain if the selectivity index can be properly defined by utilizing cultured KB cells... 

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