Malaria remains a major cause of childhood deaths in resource-limited settings. In the absence of an effective vaccine, drugs and other interventions have played very significant roles in combating the scourge of malaria. The recent reports of resistance to artemisinin necessitate the need for new antimalarial drugs with novel mechanisms of action. Towards the development of new, affordable and easily accessible antimalarial drugs for endemic regions, the Medicines for Malaria Venture (MMV) assembled a total of 400 active antimalarial compounds called the Malaria Box. The potency and the efficacy of the Malaria Box Compounds have been determined mainly using laboratory strains of P. falciparum . This study investigated the potency of twenty compounds from the Malaria Box against four clinical isolates from Ghana, using optimized in vitro growth inhibitory assays. Seven out of the 20 compounds screened had 50% inhibitory concentration (IC 50 ) below 500 nM. The most active among the selected compounds was MMV006087 (average IC 50 of 30.79 nM). Variations in the potency of the Malaria Box Compounds were observed between P. falciparum clinical isolates and Dd2 strain. We also investigated the sensitivity of the clinical isolates to chloroquine and artesunate. The N093 clinical isolate was found to be resistant to chloroquine but showed high sensitivity to artesunate. The results underscore the importance of including clinical isolates with different drug-resistant backgrounds, in addition to laboratory strains, in validating potential compounds during antimalarial compound screening programs. Graphical abstract Image 1 Highlights • MMV006087, MMV085203, MMV008956 and MMV665977 were most potent compounds in this study. • MMV006087 was the best compound in this study. • N093 clinical isolate harboured K76T mutation and was sensitive to artesunate but resistant to chloroquine. • Malaria Box Compounds have varied potency in clinical isolates and laboratory strains of P. falciparum .
【저자키워드】 clinical isolates, compounds, erythrocytes, potency, Plasmodium, malaria box,