5-Aminopyrazole-4-Carboxamide-Based Compounds Prevent the Growth of Cryptosporidium parvum

被引：11

作者：

Huang, Wenlin ^{[1
]}

Choi, Ryan ^{[2
]}

Hulverson, Matthew A. ^{[2
]}

Zhang, Zhongsheng ^{[1
]}

McCloskey, Molly C. ^{[2
]}

Schaefer, Deborah A. ^{[3
]}

Whitman, Grant R. ^{[2
]}

Barrett, Lynn K. ^{[2
]}

Vidadala, Rama Subba Rao ^{[4
]}

Riggs, Michael W. ^{[3
]}

Maly, Dustin J. ^{[1
,4
]}

Van Voorhis, Wesley C. ^{[2
]}

Ojo, Kayode K. ^{[2
]}

Fan, Erkang ^{[1
]}

机构：

[1] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[2] Univ Washington, CERID, Div Allergy & Infect Dis, Seattle, WA 98195 USA

[3] Univ Arizona, Coll Agr & Life Sci, Sch Anim & Comparat Biomed Sci, Tucson, AZ USA

[4] Univ Washington, Dept Chem, Seattle, WA 98195 USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2017年 / 61卷 / 08期

基金：

美国食品与农业研究所; 美国国家卫生研究院;

关键词：

5-aminopyrazole-4-carboxamide; bumped kinase inhibitors; Cryptosporidium parvum; BUMPED-KINASE INHIBITORS; SELECTIVE INHIBITORS; T; GONDII; C; PARVUM; BURDEN; POTENT; CDPK1; THERAPEUTICS; DISEASE; ANALOGS;

D O I：

10.1128/AAC.00020-17

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 pyrazol-opyrimidines, 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.

引用

页数：6

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