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J Med Chem. 2012 Mar 8;55(5):2416-26. doi: 10.1021/jm201713h. Epub 2012 Feb 27.

Development of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) inhibitors with potent anti-toxoplasma activity.

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1
Department of Chemistry, University of Washington, Seattle, Washington, USA.

Abstract

Toxoplasmosis is a disease of prominent health concern that is caused by the protozoan parasite Toxoplasma gondii. Proliferation of T. gondii is dependent on its ability to invade host cells, which is mediated in part by calcium-dependent protein kinase 1 (CDPK1). We have developed ATP competitive inhibitors of TgCDPK1 that block invasion of parasites into host cells, preventing their proliferation. The presence of a unique glycine gatekeeper residue in TgCDPK1 permits selective inhibition of the parasite enzyme over human kinases. These potent TgCDPK1 inhibitors do not inhibit the growth of human cell lines and represent promising candidates as toxoplasmosis therapeutics.

PMID:
22320388
PMCID:
PMC3306180
DOI:
10.1021/jm201713h
[Indexed for MEDLINE]
Free PMC Article

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