Achiral, Cheap, and Potent Inhibitors of Plasmepsins I, II, and IV

Authors

  • Christoph Boss Dr.,

    1. Drug Discovery, Chemistry & Biology, Actelion Pharmaceuticals Ltd. Gewerbestrasse 16, 4123 Allschwil, Switzerland, Fax: (+41) 61-565-6500
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  • Olivier Corminboeuf Dr.,

    1. Drug Discovery, Chemistry & Biology, Actelion Pharmaceuticals Ltd. Gewerbestrasse 16, 4123 Allschwil, Switzerland, Fax: (+41) 61-565-6500
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  • Corinna Grisostomi Dr.,

    1. Drug Discovery, Chemistry & Biology, Actelion Pharmaceuticals Ltd. Gewerbestrasse 16, 4123 Allschwil, Switzerland, Fax: (+41) 61-565-6500
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  • Solange Meyer Dr.,

    1. Drug Discovery, Chemistry & Biology, Actelion Pharmaceuticals Ltd. Gewerbestrasse 16, 4123 Allschwil, Switzerland, Fax: (+41) 61-565-6500
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  • Andrew F. Jones Dr.,

    1. Drug Discovery, Chemistry & Biology, Actelion Pharmaceuticals Ltd. Gewerbestrasse 16, 4123 Allschwil, Switzerland, Fax: (+41) 61-565-6500
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  • Lars Prade Dr.,

    1. Drug Discovery, Chemistry & Biology, Actelion Pharmaceuticals Ltd. Gewerbestrasse 16, 4123 Allschwil, Switzerland, Fax: (+41) 61-565-6500
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  • Christoph Binkert Dr.,

    1. Drug Discovery, Chemistry & Biology, Actelion Pharmaceuticals Ltd. Gewerbestrasse 16, 4123 Allschwil, Switzerland, Fax: (+41) 61-565-6500
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  • Walter Fischli Dr.,

    1. Drug Discovery, Chemistry & Biology, Actelion Pharmaceuticals Ltd. Gewerbestrasse 16, 4123 Allschwil, Switzerland, Fax: (+41) 61-565-6500
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  • Thomas Weller Dr.,

    1. Drug Discovery, Chemistry & Biology, Actelion Pharmaceuticals Ltd. Gewerbestrasse 16, 4123 Allschwil, Switzerland, Fax: (+41) 61-565-6500
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  • Daniel Bur Dr.

    1. Drug Discovery, Chemistry & Biology, Actelion Pharmaceuticals Ltd. Gewerbestrasse 16, 4123 Allschwil, Switzerland, Fax: (+41) 61-565-6500
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  • We gratefully acknowledge the excellent work by Prof. Reto Brun, Dr. Sergio Wittlin, and Christian Scheurer from the Swiss Tropical Institute.

Abstract

original image

A novel class of molecules targeting aspartic proteinases from P. falciparum is described. Synthesis of these easily available, achiral, and highly potent molecules was supported by structural information and eventually allowed the identification of compounds highly active against three vacuolar aspartic proteinases. In a red blood cell assay, the growth of P. falciparum (strain K1) could be effectively prevented.

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