Abstract
Pyronaridine, an acridine derivative, has been found effective in China for the treatment of drug-resistant falciparum malaria. The activities of pyronaridine and mepacrine were compared with those of standard antimalarial drugs in vitro against chloroquine-sensitive (CS) and chloroquine-resistant (CR) Plasmodium falciparum isolates to investigate cross resistance. The 50% inhibitory concentrations (IC(50)) against the resistant isolates were 2.8-fold higher than the sensitive isolates for pyronaridine (CS = 7.3 nM; CR = 20.5 nM) and 3.2-fold higher for mepacrine (CS = 13.3 nM; CR = 42.6 nM). These same isolates showed an 11-fold difference in sensitivity to chloroquine with mean IC(50) values of 21 nM for sensitive and 239 nM for resistant parasites. A significant correlation was observed between parasite sensitivity (IC(50)) to pyronaridine and the drugs, mepacrine, amodiaquine and chloroquine. However, the high level of activity seen with pyronaridine, even against the CR isolates, should encourage further field trials with this drug.
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