Development of Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1) Inhibitors with Potent Anti-Toxoplasma Activity

详细信息    查看全文

• 作者：Steven M. Johnson ; Ryan C. Murphy ; Jennifer A. Geiger ; Amy E. DeRocher ; Zhongsheng Zhang ; Kayode K. Ojo ; Eric T. Larson ; B. Gayani K. Perera ; Edward J. Dale ; Panqing He ; Molly C. Reid ; Anna M. W. Fox ; Natascha R. Mueller ; Ethan A. Merritt ; Erkang Fan ; Marilyn Parsons ; Wesley C. Van Voorhis ; Dustin J. Maly
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：March 8, 2012
• 年：2012
• 卷：55
• 期：5
• 页码：2416-2426
• 全文大小：570K
• 年卷期：v.55,no.5(March 8, 2012)
• ISSN：1520-4804

文摘

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.