5-Aminopyrazole-4-carboxamide-based compounds prevent the growth of Cryptosporidium parvum

Wenlin Huang, Ryan Choi, Matthew A. Hulverson, Zhongsheng Zhang, Molly C. McCloskey, Deborah A. Schaefer, Grant R. Whitman, Lynn K. Barrett, Rama Subba Rao Vidadala, Michael W Riggs, Dustin J. Maly, Wesley C. Van Voorhis, Kayode K. Ojo, Erkang Fan

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5 Scopus citations

Abstract

Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) is a promising target for drug development against cryptosporidiosis. We report a series of low-nanomolar CpCDPK1 5-aminopyrazole-4-carboxamide (AC) scaffold inhibitors that also potently inhibit C. parvum growth in vitro. Correlation between anti-CpCDPK1 and C. parvum growth inhibition, as previously reported for pyrazolopyrimidines, was not apparent. Nonetheless, lead AC compounds exhibited a substantial reduction of parasite burden in the neonatal mouse cryptosporidiosis model when dosed at 25 mg/kg.

Original languageEnglish (US)
Article numbere00020
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number8
DOIs
StatePublished - Aug 1 2017

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Keywords

  • 5-aminopyrazole-4-carboxamide
  • Bumped kinase inhibitors
  • Cryptosporidium parvum

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Huang, W., Choi, R., Hulverson, M. A., Zhang, Z., McCloskey, M. C., Schaefer, D. A., Whitman, G. R., Barrett, L. K., Vidadala, R. S. R., Riggs, M. W., Maly, D. J., Van Voorhis, W. C., Ojo, K. K., & Fan, E. (2017). 5-Aminopyrazole-4-carboxamide-based compounds prevent the growth of Cryptosporidium parvum. Antimicrobial Agents and Chemotherapy, 61(8), [e00020]. https://doi.org/10.1128/AAC.00020-17