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

Research output: Research - peer-reviewArticle

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.

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

Fingerprint

Cryptosporidium parvum
Growth
5-aminopyrazole
calcium-dependent protein kinase
Cryptosporidiosis
Protein Kinase C
Parasites
Pharmaceutical Preparations
In Vitro Techniques

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., ... Fan, E. (2017). 5-Aminopyrazole-4-carboxamide-based compounds prevent the growth of Cryptosporidium parvum. Antimicrobial Agents and Chemotherapy, 61(8), [e00020]. DOI: 10.1128/AAC.00020-17

5-Aminopyrazole-4-carboxamide-based compounds prevent the growth of Cryptosporidium parvum. / Huang, Wenlin; Choi, Ryan; Hulverson, Matthew A.; Zhang, Zhongsheng; McCloskey, Molly C.; Schaefer, Deborah A.; Whitman, Grant R.; Barrett, Lynn K.; Vidadala, Rama Subba Rao; Riggs, Michael W.; Maly, Dustin J.; Van Voorhis, Wesley C.; Ojo, Kayode K.; Fan, Erkang.

In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 8, e00020, 01.08.2017.

Research output: Research - peer-reviewArticle

Huang, W, Choi, R, Hulverson, MA, Zhang, Z, McCloskey, MC, Schaefer, DA, Whitman, GR, Barrett, LK, Vidadala, RSR, Riggs, MW, Maly, DJ, Van Voorhis, WC, Ojo, KK & Fan, E 2017, '5-Aminopyrazole-4-carboxamide-based compounds prevent the growth of Cryptosporidium parvum' Antimicrobial Agents and Chemotherapy, vol 61, no. 8, e00020. DOI: 10.1128/AAC.00020-17
Huang W, Choi R, Hulverson MA, Zhang Z, McCloskey MC, Schaefer DA et al. 5-Aminopyrazole-4-carboxamide-based compounds prevent the growth of Cryptosporidium parvum. Antimicrobial Agents and Chemotherapy. 2017 Aug 1;61(8). e00020. Available from, DOI: 10.1128/AAC.00020-17
Huang, Wenlin ; Choi, Ryan ; Hulverson, Matthew A. ; Zhang, Zhongsheng ; McCloskey, Molly C. ; Schaefer, Deborah A. ; Whitman, Grant R. ; Barrett, Lynn K. ; Vidadala, Rama Subba Rao ; Riggs, Michael W. ; Maly, Dustin J. ; Van Voorhis, Wesley C. ; Ojo, Kayode K. ; Fan, Erkang. / 5-Aminopyrazole-4-carboxamide-based compounds prevent the growth of Cryptosporidium parvum. In: Antimicrobial Agents and Chemotherapy. 2017 ; Vol. 61, No. 8.
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