Fig. 5.

Chemical validation of PSAC as an antimalarial target with a family of dibenzothiazepinone derivatives. In vitro parasite growth inhibition pIC₅₀ values for each of 72 dibenzothiazepinone derivatives is plotted against pK_0.5 values determined from dose responses for inhibition of osmotic lysis in the sorbitol lysis solution supplemented with 5% human serum. pIC₅₀ and pK_0.5 were calculated as −log(IC₅₀) and −log(K_0.5) in molar units, respectively; the most effective compounds are at the top right of the plot. Compound 2, the parent compound for this family, is shown as a star. Although some derivatives have additional “off-target” effects (e.g., compounds to the upper left of the profile), there is a significant correlation between channel inhibition and parasite killing.