Potent and Selective Inhibition of Cysteine Proteases from Plasmodium falciparum and Trypanosoma brucei

被引：32

作者：

Ehmke, Veronika ^{[1
]}

Heindl, Cornelia ^{[2
]}

Rottmann, Matthias ^{[3
,4
]}

Freymond, Celine ^{[3
,4
]}

Schweizer, W. Bernd ^{[1
]}

Brun, Reto ^{[3
,4
]}

Stich, August ^{[5
]}

Schirmeister, Tanja ^{[2
]}

Diederich, Francois ^{[1
]}

机构：

[1] Swiss Fed Inst Technol, Organ Chem Lab, CH-8093 Zurich, Switzerland

[2] Univ Wurzburg, Inst Pharm & Food Chem, D-97074 Wurzburg, Germany

[3] Swiss Trop & Publ Hlth Inst, CH-4002 Basel, Switzerland

[4] Univ Basel, CH-4003 Basel, Switzerland

[5] Med Mission Inst, Dept Trop Med, D-97074 Wurzburg, Germany

来源：

CHEMMEDCHEM | 2011年 / 6卷 / 02期

基金：

瑞士国家科学基金会;

关键词：

African trypanosomiasis; cysteine proteases; inhibitors; malaria; structure-based design; VACUOLE PLASMEPSINS; HEMOGLOBINASE; RHODESAIN;

D O I：

10.1002/cmdc.201000449

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Treating tropical diseases: Structure-based design afforded highly active triazine nitrile inhibitors of the protozoan cysteine proteases falcipain-2 and rhodesain. Optimization of the occupancy of the S1, S2, and S3 pockets of these enzymes yielded inhibitory constants in the low nanomolar activity range. The new ligands are selective against other related proteases and exhibit in vitro activities against the protozoan parasites. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：273 / 278

页数：6

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