ml400315s_si_001.pdf (326.89 kB)
Potent and Selective Inhibitors of CDPK1 from T. gondii and C. parvum Based on a 5‑Aminopyrazole-4-carboxamide Scaffold
journal contribution
posted on 2014-01-09, 00:00 authored by Zhongsheng Zhang, Kayode
K. Ojo, RamaSubbaRao Vidadala, Wenlin Huang, Jennifer A. Geiger, Suzanne Scheele, Ryan Choi, Molly C. Reid, Katelyn R. Keyloun, Kasey Rivas, Latha Kallur Siddaramaiah, Kenneth M. Comess, Kenneth P. Robinson, Philip J. Merta, Lemma Kifle, Wim G. J. Hol, Marilyn Parsons, Ethan A. Merritt, Dustin J. Maly, Christophe L. M. J. Verlinde, Wesley C. Van Voorhis, Erkang Fan5-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.