Comparison of hematin-targeting properties of pynacrine, an acridine analog of the benzonaphthyridine antimalarial pyronaridine

The hematin-targeting properties of pynacrine, an acridine analog of the schizontocidal antimalarial drug, pyronaridine, were evaluated to probe the role of the latterʹs benzonaphthyridine moiety. Pynacrine was as active as pyronaridine in inhibiting glutathione-induced hematin degradation and in enhancing hematin-mediated membrane lysis. It formed a 1:2 complex with hematin but was 50-fold less effective in inhibiting β-hematin formation. However, pynacrine was as potent as pyronaridine in inhibiting intra-erythrocytic Plasmodium falciparum growth in culture, suggesting that it has other off-target(s) effects.