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

Rebecca L. Clements, Vincent Streva, Peter Dumoulin, Weigang Huang, Edward Owens, Dipak K. Raj, Barbara Burleigh, Manuel Llinás, Elizabeth A. Winzeler, Qisheng Zhang, Jeffrey D. Dvorin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)956-962
Number of pages7
JournalJournal of Infectious Diseases
Volume221
Issue number6
DOIs
StatePublished - Mar 15 2020

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

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    Clements, R. L., Streva, V., Dumoulin, P., Huang, W., Owens, E., Raj, D. K., Burleigh, B., Llinás, M., Winzeler, E. A., Zhang, Q., & Dvorin, J. D. (2020). A Novel Antiparasitic Compound Kills Ring-Stage Plasmodium falciparum and Retains Activity against Artemisinin-Resistant Parasites. Journal of Infectious Diseases, 221(6), 956-962. https://doi.org/10.1093/infdis/jiz534