Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity

Abstract

A series of novel imidazoisoquinolinone derivatives were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive GHA strain of Plasmodium falciparum. Compounds 2, 4, 6, 9, and 17 revealed moderate to good activities in the micromolar range. Binding interaction between these active compounds and heme were determined and correlated with antimalarial activity. A good correlation (r = 0.98) was observed between antimalarial activity and the heme dissociation constants (K d). These suggest that antimalarial mode of action of this class of compounds appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation.