Identification of Fast-Acting 2,6-Disubstituted Imidazopyridines That Are Efficacious in the in Vivo Humanized Plasmodium falciparum NODscidIL2R?null Mouse Model of Malaria Articles uri icon

authors

  • NCHINDA, ALOYSIUS T.
  • LE MANACH, CLAIRE
  • PAQUET, TANYA
  • CABRERA, DIEGO GONZALEZ
  • WICHT, KATHRYN J.
  • BRUNSCHWIG, CHRISTEL
  • NJOROGE, MATHEW
  • ABAY, EFREM
  • TAYLOR, DALE
  • LAWRENCE, NINA
  • WITTLIN, SERGIO
  • JIMÉNEZ DÍAZ, MARÍA BELÉN
  • SANTOS MARTINEZ, MARIA
  • FERRER BAZAGA, SANTIAGO
  • ANGULO BARTUREN, ÍÑIGO
  • LAFUENTE-MONASTERIO, MARIA JOSE
  • DUFFY, JAMES
  • BURROWS, JEREMY
  • STREET, LESLIE J.
  • CHIBALE, KELLY

publication date

  • May 2018

start page

  • 4213

end page

  • 4227

issue

  • 9

volume

  • 61

International Standard Serial Number (ISSN)

  • 0022-2623

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

abstract

  • Optimization of a chemical series originating from whole-cell phenotypic screening against the human malaria parasite, Plasmodium falciparum, led to the identification of two promising 2,6-disubstituted imidazopyridine compounds, 43 and 74. These compounds exhibited potent activity against asexual blood stage parasites that, together with their in vitro absorption, distribution, metabolism, and excretion (ADME) properties, translated to in vivo efficacy with clearance of parasites in the PfSCID mouse model for malaria within 48 h of treatment.

subjects

  • Biology and Biomedicine
  • Medicine

keywords

  • optimization; assay