TY - JOUR
T1 - 5-Aminopyrazole-4-carboxamide-based compounds prevent the growth of Cryptosporidium parvum
AU - Huang, Wenlin
AU - Choi, Ryan
AU - Hulverson, Matthew A.
AU - Zhang, Zhongsheng
AU - McCloskey, Molly C.
AU - Schaefer, Deborah A.
AU - Whitman, Grant R.
AU - Barrett, Lynn K.
AU - Vidadala, Rama Subba Rao
AU - Riggs, Michael W.
AU - Maly, Dustin J.
AU - Van Voorhis, Wesley C.
AU - Ojo, Kayode K.
AU - Fan, Erkang
N1 - Publisher Copyright:
© 2017 American Society for Microbiology. All Rights Reserved.
PY - 2017/8
Y1 - 2017/8
N2 - 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.
AB - 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.
KW - 5-aminopyrazole-4-carboxamide
KW - Bumped kinase inhibitors
KW - Cryptosporidium parvum
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UR - http://www.scopus.com/inward/citedby.url?scp=85026375904&partnerID=8YFLogxK
U2 - 10.1128/AAC.00020-17
DO - 10.1128/AAC.00020-17
M3 - Article
C2 - 28533246
AN - SCOPUS:85026375904
SN - 0066-4804
VL - 61
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 8
M1 - e00020
ER -