Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies

Due to the recent advances of atovaquone, a naphthoquinone, through clinical trialsas treatment for malarial infection, 19 quinone derivatives with previously reportedstructures were also evaluated for blood schizonticide activity against the malariaparasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylaminonaphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol(13) and phenazines (12-20). Their cytotoxicities were also evaluated against humanhepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highestactivity against P. falciparum chloroquine-resistant blood-stage parasites (cloneW2), indicated by their low inhibitory concentration for 50% (IC₅₀) ofparasite growth. The therapeutic potential of the active compounds was evaluatedaccording to the selectivity index, which is a ratio of the cytotoxicity minimumlethal dose which eliminates 50% of cells and the in vitro IC₅₀.Naphthoquinones 2 and 5, with activities similar to the reference antimalarialchloroquine, were also active against malaria in mice and suppressed parasitaemia bymore than 60% in contrast to compound 11 which was inactive. Based on their in vitroand in vivo activities, compounds 2 and 5 are considered promising molecules forantimalarial treatment and warrant further study.