Novel diaryl ureas with efficacy in a mouse model of malaria

John W. Anderson, Dimitri Sarantakis, Jacek Terpinski, T. R. Santha Kumar, Han Chun Tsai, MacK Kuo, Arba L. Ager, William R. Jacobs, Guy A. Schiehser, Sean Ekins, James C. Sacchettini, David P. Jacobus, David A. Fidock, Joel S. Freundlich

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16 Scopus citations

Abstract

Exploration of triclosan analogs has led to novel diaryl ureas with significant potency against in vitro cultures of drug-resistant and drug-sensitive strains of the human malaria parasite Plasmodium falciparum. Compound 18 demonstrated EC50 values of 37 and 55 nM versus in vitro cultured parasite strains and promising in vivo efficacy in a Plasmodium berghei antimalarial mouse model, with >50% survival at day 31 post-treatment when administered subcutaneously at 256 mg/kg. This series of compounds provides a chemical scaffold of novel architecture, as validated by cheminformatics analysis, to pursue antimalarial drug discovery efforts.

Original languageEnglish (US)
Pages (from-to)1022-1025
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number4
DOIs
Publication statusPublished - Feb 15 2013

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Keywords

  • Diaryl urea
  • Drug discovery
  • Malaria
  • Plasmodium falciparum

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Anderson, J. W., Sarantakis, D., Terpinski, J., Santha Kumar, T. R., Tsai, H. C., Kuo, M., ... Freundlich, J. S. (2013). Novel diaryl ureas with efficacy in a mouse model of malaria. Bioorganic and Medicinal Chemistry Letters, 23(4), 1022-1025. https://doi.org/10.1016/j.bmcl.2012.12.022