A Novel Antiparasitic Compound Kills Ring-Stage Plasmodium falciparum and Retains Activity Against Artemisinin-Resistant Parasites.

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Journal:
The Journal of infectious diseases, Volume: 221, Issue: 6
Published:
March 2, 2020
PMID:
31616928
Authors:
Rebecca L Clements RL, Vincent Streva V, Peter Dumoulin P, Weigang Huang W, Edward Owens E, Dipak K Raj DK, Barbara Burleigh B, Manuel Llinás M, Elizabeth A Winzeler EA, Qisheng Zhang Q, Jeffrey D Dvorin JD
Abstract:

Spreading antimalarial resistance threatens effective treatment of malaria, an infectious disease caused by Plasmodium parasites. We identified a compound, BCH070, that inhibits asexual growth of multiple antimalarial-resistant strains of Plasmodium falciparum (half maximal inhibitory concentration [IC50] = 1-2 µM), suggesting that BCH070 acts via a novel mechanism of action. BCH070 preferentially kills early ring-form trophozoites, and, importantly, equally inhibits ring-stage survival of wild-type and artemisinin-resistant parasites harboring the PfKelch13:C580Y mutation. Metabolomic analysis demonstrates that BCH070 likely targets multiple pathways in the parasite. BCH070 is a promising lead compound for development of new antimalarial combination therapy that retains activity against artemisinin-resistant parasites.