Antimalarial effect of synthetic endoperoxide on synchronized Plasmodium chabaudi infected mice

Abstract

The discovery of new antimalarial drugs can be developed using asynchronized <i>Plasmodium berghei</i> malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on <i>P. chabaudi</i> parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich <i>P. chabaudi</i> parasites and asynchronized <i>P. berghei</i> parasites using the 4-day suppressive test. The ED₅₀ values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich <i>P. chabaudi</i> parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using <i>P. chabaudi</i> in mice. The results show that <i>P. chabaudi</i> is a reliable model for the characterization of stage-specific antimalarial effects.