Figure 6.

Speed and basis of killing of selected compounds. (a) IC₅₀ values for test compounds washed out at various times (IC₅₀^t) relative to that with no washout (IC₅₀^72h). Where no bar is shown, there was no inhibition of parasite growth after that length of exposure. (b) Trend of increasing exchangeable heme levels as a function of prolonged duration of killing. (c) Effects of externally introduced Fe(III)PPIX and Zn(II)PPIX on parasite survival with and without NAC. (d) Effects of varying concentration of NAC on the relative IC₅₀ of chloroquine (1). (e) Lack of effect of NAC on toxicity of chloroquine (1) in CHO cells. (f) Protective effect of NAC and potentiating effect of Luperox® on parasites in the presence of chloroquine (1). NAC was found to abrogate the effect of Luperox®. (g) Isobolograms showing strong antagonism between compound 4 & chloroquine (1) and compound 13 & chloroquine (1) but an additive effect between the non-hemozoin inhibitor 5 & chloroquine (1). Dotted line represents one standard deviation about the line. (h) Protective effect of NAC on the effects of compound 4 and potentiating effect of Luperox®, but lack of effect of either NAC or Luperox® on the activities of compounds 5 and 13. Statistical significance, calculated using a two-tailed t-test (error bars showing 95% CI) is expressed using asterisks. * P < 0.05, ** P < 0.01, *** P < 0.001.