Open-source discovery of chemical leads for next-generation chemoprotective antimalarials.

ABSTRACT: To discover leads for next-generation chemoprotective antimalarial drugs, we tested more than 500,000 compounds for their ability to inhibit liver-stage development of luciferase-expressing Plasmodium spp. parasites (681 compounds showed a half-maximal inhibitory concentration of less than 1 micromolar). Cluster analysis identified potent and previously unreported scaffold families as well as other series previously associated with chemoprophylaxis. Further testing through multiple phenotypic assays that predict stage-specific and multispecies antimalarial activity distinguished compound classes that are likely to provide symptomatic relief by reducing asexual blood-stage parasitemia from those which are likely to only prevent malaria. Target identification by using functional assay

SUBMITTER: Antonova-Koch Y 

PROVIDER: S-EPMC6516198 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature