Benzoylbenzimidazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1.
Bioorg Med Chem Lett
; 22(16): 5264-7, 2012 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-22795629
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.
Full text:
1
Database:
MEDLINE
Main subject:
Protein Kinases
/
Toxoplasma
/
Benzimidazoles
/
Protozoan Proteins
/
Cryptosporidium parvum
/
Protein Kinase Inhibitors
Limits:
Humans
Language:
En
Year:
2012
Type:
Article