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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.
Affiliation
  • Huang W; Department of Biochemistry, University of Washington, Seattle, Washington, USA.
  • Choi R; Division of Allergy & Infectious Diseases, Center for Emerging & Reemerging Infectious Diseases (CERID), University of Washington, Seattle, Washington, USA.
  • Hulverson MA; Division of Allergy & Infectious Diseases, Center for Emerging & Reemerging Infectious Diseases (CERID), University of Washington, Seattle, Washington, USA.
  • Zhang Z; Department of Biochemistry, University of Washington, Seattle, Washington, USA.
  • McCloskey MC; Division of Allergy & Infectious Diseases, Center for Emerging & Reemerging Infectious Diseases (CERID), University of Washington, Seattle, Washington, USA.
  • Schaefer DA; School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, Arizona, USA.
  • Whitman GR; Division of Allergy & Infectious Diseases, Center for Emerging & Reemerging Infectious Diseases (CERID), University of Washington, Seattle, Washington, USA.
  • Barrett LK; Division of Allergy & Infectious Diseases, Center for Emerging & Reemerging Infectious Diseases (CERID), University of Washington, Seattle, Washington, USA.
  • Vidadala RSR; Department of Chemistry, University of Washington, Seattle, Washington, USA.
  • Riggs MW; School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, Arizona, USA.
  • Maly DJ; Department of Biochemistry, University of Washington, Seattle, Washington, USA.
  • Van Voorhis WC; Department of Chemistry, University of Washington, Seattle, Washington, USA.
  • Ojo KK; Division of Allergy & Infectious Diseases, Center for Emerging & Reemerging Infectious Diseases (CERID), University of Washington, Seattle, Washington, USA.
  • Fan E; Division of Allergy & Infectious Diseases, Center for Emerging & Reemerging Infectious Diseases (CERID), University of Washington, Seattle, Washington, USA ojo67kk@u.washington.edu erkang@u.washington.edu.
Antimicrob Agents Chemother ; 61(8)2017 08.
Article in En | MEDLINE | ID: mdl-28533246
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Kinases / Cryptosporidium parvum / Cryptosporidiosis / Protein Kinase Inhibitors / Antiprotozoal Agents Limits: Animals Language: En Journal: Antimicrob Agents Chemother Year: 2017 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein Kinases / Cryptosporidium parvum / Cryptosporidiosis / Protein Kinase Inhibitors / Antiprotozoal Agents Limits: Animals Language: En Journal: Antimicrob Agents Chemother Year: 2017 Type: Article Affiliation country: United States