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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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
StatePublished - Feb 15 2013

Fingerprint

Antimalarials
Malaria
Urea
Parasites
Triclosan
Plasmodium berghei
Falciparum Malaria
Drug Discovery
Scaffolds
Pharmaceutical Preparations
Survival
In Vitro Techniques
compound 18

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

Novel diaryl ureas with efficacy in a mouse model of malaria. / Anderson, John W.; Sarantakis, Dimitri; Terpinski, Jacek; Santha Kumar, T. R.; Tsai, Han Chun; Kuo, MacK; Ager, Arba L.; Jacobs, William R.; Schiehser, Guy A.; Ekins, Sean; Sacchettini, James C.; Jacobus, David P.; Fidock, David A.; Freundlich, Joel S.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 4, 15.02.2013, p. 1022-1025.

Research output: Contribution to journalArticle

Anderson, JW, Sarantakis, D, Terpinski, J, Santha Kumar, TR, Tsai, HC, Kuo, M, Ager, AL, Jacobs, WR, Schiehser, GA, Ekins, S, Sacchettini, JC, Jacobus, DP, Fidock, DA & Freundlich, JS 2013, 'Novel diaryl ureas with efficacy in a mouse model of malaria', Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 4, pp. 1022-1025. https://doi.org/10.1016/j.bmcl.2012.12.022
Anderson JW, Sarantakis D, Terpinski J, Santha Kumar TR, Tsai HC, Kuo M et al. Novel diaryl ureas with efficacy in a mouse model of malaria. Bioorganic and Medicinal Chemistry Letters. 2013 Feb 15;23(4):1022-1025. https://doi.org/10.1016/j.bmcl.2012.12.022
Anderson, John W. ; Sarantakis, Dimitri ; Terpinski, Jacek ; Santha Kumar, T. R. ; Tsai, Han Chun ; Kuo, MacK ; Ager, Arba L. ; Jacobs, William R. ; Schiehser, Guy A. ; Ekins, Sean ; Sacchettini, James C. ; Jacobus, David P. ; Fidock, David A. ; Freundlich, Joel S. / Novel diaryl ureas with efficacy in a mouse model of malaria. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 4. pp. 1022-1025.
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