Fig. 1: High-throughput screening based on mitochondrial staining and cell deformability identifies compounds with both killing effect and stiffening activity on P. falciparum late gametocytes.

Screening progression cascade of three different libraries: Malaria Pathogen Box (A), Kinase Inhibitors Box (B), and ReFrame library (C). A 3 hits from primary screening were submitted to dose-response analysis along with 12 compounds found active in some but not all screening replicates. The 3 hits were confirmed but none of them was selected for further post-screening validation. B Four hits from primary screening along with 5 compounds found active in some but not all screening replicates were submitted to dose-response analysis raising 3 confirmed hits. None of them was selected for further post-screening validation. C 112 hits from primary screening were submitted to dose-response analysis, raising 74 confirmed hits. 63 compounds with uninterpretable results during primary screening were added to the hits for dose-response analysis raising additional two confirmed hits. The 76 confirmed hits were allocated to seven groups (panels on the right), based on their activity and molecular target. For each group, one representative hit has been selected for illustration. Hit scoring based on route of administration, safety in human subjects, and pharmacokinetics resulted in the selection of 3 drugs submitted to final confirmation experiments (dark blue).