Potent and Selective Inhibitors of CDPK1 from T. gondii and C. parvum Based on a 5-Aminopyrazole-4-carboxamide Scaffold

作者：Zhang Zhongsheng; Ojo Kayode K; Vidadala RamaSubbaRao; Huang Wenlin; Geiger Jennifer A; Scheele Suzanne; Choi Ryan; Reid Molly C; Keyloun Katelyn R; Rivas Kasey; Siddaramaiah Latha Kallur; Comess Kenneth M; Robinson Kenneth P; Merta Philip J; Kifle Lemma; Hol Wim G J; Parsons Marilyn; Merritt Ethan A; Maly Dustin J; Verlinde Christophe L M J; Van Voorhis Wesley C^*; Fan Erkang

来源：ACS Medicinal Chemistry Letters, 2014, 5(1): 40-44.

DOI：10.1021/ml400315s

• Toxoplasma gondii
• Cryptosporidium parvum
• calcium-dependent protein kinase-1
• enzyme inhibitor
• selectivity

5-Aminopyrazole-4-carboxamide was used as an alternative scaffold to substitute for the pyrazolopyrimidine of a known "bumped kinase inhibitor" to create selective inhibitors of calcium-dependent protein kinase-1 from both Toxoplasma gondii and Cryptosporidium parvum. Compounds with low nanomolar inhibitory potencies against the target enzymes were obtained. The most selective inhibitors also exhibited submicromolar activities in T. gondii cell proliferation assays and were shown to be nontoxic to mammalian cells.

• 出版日期2014-1