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

Abstract

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 <i>Toxoplasma gondii</i> and <i>Cryptosporidium parvum</i>. Compounds with low nanomolar inhibitory potencies against the target enzymes were obtained. The most selective inhibitors also exhibited submicromolar activities in <i>T. gondii</i> cell proliferation assays and were shown to be non-toxic to mammalian cells.