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

Abstract

© 2014 Elsevier B.V. The hematin-targeting properties of pynacrine, an acridine analog of the schizontocidal antimalarial drug, pyronaridine, were evaluated to probe the role of the latter's 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 intraerythrocytic Plasmodium falciparum growth in culture, suggesting that it has other off-target(s) effects.