ACS Med Chem Lett. 2014 Jan 9;5(1):40-44.

Potent and selective inhibitors of CDPK1 from T. gondii and C. parvum based on a 5-aminopyrazole-4-carboxamide scaffold

Zhang Z1, Ojo KK2, Vidadala R3, Huang W1, Geiger JA4, Scheele S4, Choi R2, Reid MC2, Keyloun KR2, Rivas K2, Siddaramaiah LK1, Comess KM5, Robinson KP5, Merta PJ5, Kifle L5, Hol WG1, Parsons M4, Merritt EA1, Maly DJ3, Verlinde CL1, Van Voorhis WC2, Fan E1.

Author information

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 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 non-toxic to mammalian cells.

KEYWORDS:

Calcium-dependent protein kinase-1, Cryptosporidium parvum, Enzyme inhibitor, Selectivity, Toxoplasma gondii

PMID:

 

24494061

 

[PubMed]