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Home ยป Benzoylbenzimidazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1.

Benzoylbenzimidazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1.

TitleBenzoylbenzimidazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1.
Publication TypeJournal Article
Year of Publication2012
AuthorsZhang, Z, Ojo, KK, Johnson, SM, Larson, ET, He, P, Geiger, JA, Castellanos-Gonzalez, A, White, CA, Parsons, M, Merritt, EA, Maly, DJ, Verlinde, CLMJ, Van Voorhis, WC, Fan, E
JournalBioorg Med Chem Lett
Volume22
Issue16
Pagination5264-7
Date Published2012 Aug 15
ISSN1464-3405
KeywordsBenzimidazoles, Cryptosporidium parvum, Drug Design, Humans, Protein Binding, Protein Kinase Inhibitors, Protein Kinases, Proto-Oncogene Proteins c-abl, Protozoan Proteins, Solubility, src-Family Kinases, Structure-Activity Relationship, Toxoplasma
Abstract

Calcium-dependent protein kinase-1 (CDPK1) from Cryptosporidium parvum (CpCDPK1) and Toxoplasma gondii (TgCDPK1) have become attractive targets for discovering selective inhibitors to combat infections caused by these protozoa. We used structure-based design to improve a series of benzoylbenzimidazole-based compounds in terms of solubility, selectivity, and potency against CpCDPK1 and TgCDPK1. The best inhibitors show inhibitory potencies below 50 nM and selectivity well above 200-fold over two human kinases with small gatekeeper residues.
DOI10.1016/j.bmcl.2012.06.050
Alternate JournalBioorg. Med. Chem. Lett.
PubMed ID22795629