Rocaglates as dual-targeting agents for experimental cerebral malaria

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Abstract
Significance: Severe complications of malaria, such as anemia and cerebral malaria (CM) (neuroinflammation), are responsible for ∼25% of infant mortality in certain regions of Africa. Notwithstanding current effective antiplasmodial treatment, drug resistance is on the increase in the Plasmodium parasites, and therapy to treat CM is nonexistent. Here, we show that rocaglates derived from a natural product originally identified from plants of the Aglaia species, effectively block blood-stage parasite replication in several mouse models and in infected human RBCs. Importantly, neurological inflammation is mitigated and survival is promoted in experimental CM, highlighting the strong potential of this class of compounds to treat complicated malaria.
Funding Information
  • Gouvernement du Canada | Canadian Institutes of Health Research (Foundation Grant to Dr Philippe Gros)
  • Gouvernement du Canada | Canadian Institutes of Health Research (FDN-148366)
  • HHS | National Institutes of Health (R35 GM118173)
  • HHS | National Institutes of Health (R24 GM111625)
  • Gouvernement du Canada | Canadian Institutes of Health Research (FDN-148439)
  • Gouvernement du Canada | Canadian Institutes of Health Research (FDN-148472)

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