5-Aminopyrazole-4-Carboxamide-Based Compounds Prevent the Growth of Cryptosporidium parvum
5-Aminopyrazole-4-Carboxamide-Based Compounds Prevent the Growth of Cryptosporidium parvum
复制标题
DOI：
10.1128/aac.00020-17
复制
发表时间：
2017-08-01
影响因子：
4.9
通讯作者：
Fan, Erkang
中科院分区：
文献类型：
--
作者：
Huang, Wenlin;Choi, Ryan;Fan, Erkang
微小隐孢子虫钙依赖蛋白激酶1（CpCDPK 1）是一个很有前途的抗隐孢子虫病药物开发靶点。我们报道了一系列低纳摩尔CpCDPK 1 5-氨基吡唑-4-甲酰胺（AC）支架抑制剂，也有效抑制C。小孢子体外生长。抗CpCDPK 1抗体与C.如先前报道的吡唑-嘧啶类对小孢子生长的抑制作用不明显。尽管如此，当以25 mg/kg剂量给药时，AC铅化合物在新生小鼠隐孢子虫病模型中表现出寄生虫负荷的显著降低。
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.