Antimalarial activity of thioacridone compounds related to the acronycine alkaloid Original Research Article

A series of thioacridone compounds that were previously shown to have DNA binding interaction, were screened for antimalarial activity. The new compounds were assessed for in vitro antimalarial activity against a chloroquine sensitive (D10) strain of the malaria parasite Plasmodium falciparum, using a lactate dehydrogenase (PfLDH) assay. In the series, the IC50 values ranged from 0.4 to 27 μg/ml. 1-(2-Dimethylaminoethylamino)-9(10H)-thioacridone was found to be the most potent against P. falciparum (D10) with an IC50 value of 0.4 μg/ml. This compound was also evaluated against a South African chloroquine resistant (RSA 11) P. falciparum strain and was found to have an IC50 value of 1 μg/ml, compared with 0.16 μg/ml for chloroquine. Quantitative structure–activity relationships of this series were also investigated and a multiple linear regression r2 of 0.58 was found for the best fit equation. The most potent compound, 1-(2-dimethylaminoethylamino)-9(10H)-thioacridone, was docked into the chloroquine binding site of PfLDH and it was found that the slightly lower activity of this compound, compared with chloroquine, is likely due to steric interference within a restricted binding pocket.