Title
Benzoylbenzimidazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1
Date Issued
15 August 2012
Access level
open access
Resource Type
research article
Author(s)
Zhang Z.
Ojo K.K.
Johnson S.M.
Larson E.T.
He P.
Geiger J.A.
Castellanos-Gonzalez A.
Parsons M.
Merritt E.A.
Maly D.J.
Verlinde C.L.M.J.
Van Voorhis W.C.
Fan E.
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. © 2012 Elsevier B.V. All rights reserved.
Start page
5264
End page
5267
Volume
22
Issue
16
Language
English
OCDE Knowledge area
Bioquímica, Biología molecular
Subjects
Scopus EID
2-s2.0-84864397034
PubMed ID
Source
Bioorganic and Medicinal Chemistry Letters
ISSN of the container
0960894X
Sponsor(s)
Funding text
This work is supported by the National Institutes of Health grants R01AI089441 (E.A.M. and W.C.V.V.) and R01GM086858 (D.J.M.). J.A.G. was supported by a training grant from the National Institute of Allergy and Infectious Diseases (Grant T32AI007509). We thank Dr. Suzanne Scheele for technical assistance.
Sources of information:
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