| Literature DB >> 31616928 |
Rebecca L Clements1,2, Vincent Streva2, Peter Dumoulin3, Weigang Huang4, Edward Owens5, Dipak K Raj6, Barbara Burleigh3, Manuel Llinás5,7, Elizabeth A Winzeler8, Qisheng Zhang4, Jeffrey D Dvorin2,9.
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.Entities:
Keywords: zzm321990 Plasmodium falciparumzzm321990 ; antimalarial; artemisinin resistance; malaria; ring-stage survival
Mesh:
Substances:
Year: 2020 PMID: 31616928 PMCID: PMC7050989 DOI: 10.1093/infdis/jiz534
Source DB: PubMed Journal: J Infect Dis ISSN: 0022-1899 Impact factor: 5.226