Calcium dysregulation is the critical initiator in high dose chloroquine-induced programmed cell death of Plasmodium falciparum

We investigated an alternative cell death mechanism triggered by micromolar concentrations of the antimalarial chloroquine (CQ) in Plasmodium falciparum. Three “hit” compounds from the Medicines for Malaria Venture (MMV) Pathogen Box were further characterized, leading to the identification of the top-hit compound, MMV085071. Ten analogues of this compound were evaluated using dose-response assays, and one lead analogue, MMV1545561, was selected as the top lead. Transcriptomic changes were analyzed following treatment of parasites with 3 µM of CQ, MMV085071, and MMV1545561 for 4 hours, starting at 32 hours-post-invasion. The raw RNA-seq data from this study is provided below.

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