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

被引：41

作者：

Zhang, Zhongsheng ^{[2
]}

Ojo, Kayode K. ^{[1
]}

Johnson, Steven M. ^{[3
]}

Larson, Eric T. ^{[2
]}

He, Penqing ^{[1
]}

Geiger, Jennifer A. ^{[4
]}

Castellanos-Gonzalez, Alejandro ^{[5
]}

White, A. Clinton, Jr. ^{[5
]}

Parsons, Marilyn ^{[4
]}

Merritt, Ethan A. ^{[2
]}

Maly, Dustin J. ^{[3
]}

Verlinde, Christophe L. M. J. ^{[2
]}

Van Voorhis, Wesley C. ^{[1
]}

Fan, Erkang ^{[2
]}

机构：

[1] Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA

[2] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[3] Univ Washington, Dept Chem, Seattle, WA 98195 USA

[4] Seattle Biomed Res Inst, Seattle, WA 98109 USA

[5] Univ Texas Med Branch, Dept Internal Med, Div Infect Dis, Galveston, TX 77555 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 16期

基金：

美国国家卫生研究院;

关键词：

Cryptosporidium parvum; Toxoplasma gondii; Calcium-dependent protein kinase-1; Enzyme inhibitor; Selectivity; DESIGN; POTENT; CDPK1;

D O I：

10.1016/j.bmcl.2012.06.050

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：5264 / 5267

页数：4

共 39 条

[1] Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors
Ojo, Kayode K.
Larson, Eric T.
Keyloun, Katelyn R.
Castaneda, Lisa J.
DeRocher, Amy E.
Inampudi, Krishna K.
Kim, Jessica E.
Arakaki, Tracy L.
Murphy, Ryan C.
Zhang, Li
Napuli, Alberto J.
Maly, Dustin J.
Verlinde, Christophe L. M. J.
Buckner, Frederick S.
Parsons, Marilyn
Hol, Wim G. J.
Merritt, Ethan A.
Van Voorhis, Wesley C.
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (05) : 602 - U102
[2] A novel toxoplasma gondii calcium-dependent protein kinase
Tzen, M.
Benarous, R.
Dupouy-Camet, J.
Roisin, M. P.
PARASITE, 2007, 14 (02) : 141 - 147
[3] The calcium-dependent protein kinase 1 from Toxoplasma gondii as target for structure-based drug design
Cardew, Emily M.
Verlinde, Christophe L. M. J.
Pohl, Ehmke
PARASITOLOGY, 2018, 145 (02) : 210 - 218
[4] Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii
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Zhang, Chao
Lopez, Michael S.
Tang, Keliang
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Wang, Qiuling
Wildman, Scott A.
Shokat, Kevan M.
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JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (07) : 3068 - 3077
[5] Characterization of Three Calcium-Dependent Protein Kinases of Cryptosporidium parvum
Zhang, Qiang
Shao, Qian
Guo, Yaqiong
Li, Na
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Su, Jiayuan
Xu, Rui
Zhang, Ziding
Xiao, Lihua
Feng, Yaoyu
FRONTIERS IN MICROBIOLOGY, 2021, 11
[6] Imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1 decrease the parasite burden in mice with acute toxoplasmosis
Moine, Esperance
Moire, Nathalie
Dimier-Poisson, Isabelle
Brunet, Kevin
Couet, William
Colas, Cyril
Van Langendonck, Nathalie
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Heraut, Bruno
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INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2018, 48 (07) : 561 - 568
[7] Development of new highly potent imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1
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[8] A Novel Calcium-Dependent Protein Kinase 1 Inhibitor Potently Prevents Toxoplasma gondii Transmission to Foetuses in Mouse
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Moire, Nathalie
Baron, Firmin
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MOLECULES, 2021, 26 (14):
[9] Characterization of Calcium-Dependent Protein Kinases 3, a Protein Involved in Growth of Cryptosporidium parvum
Zhang, Qiang
Guo, Yaqiong
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Li, Yu
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[10] Toxoplasma Calcium-Dependent Protein Kinase 1 Inhibitors: Probing Activity and Resistance Using Cellular Thermal Shift Assays
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Geiger, Jennifer A.
DeRocher, Amy E.
Choi, Ryan
Smith, Tess R.
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Vidadala, Rama Subba Rao
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Ojo, Kayode K.
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ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2018, 62 (06) : e00051 - e00118

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