Allicin and derivates are cysteine protease inhibitors with antiparasitic activity

Thilo Waag; Christoph Gelhaus; Jennifer Rath; August Stich; Matthias Leippe; Tanja Schirmeister

doi:10.1016/j.bmcl.2010.07.062

Allicin and derivates are cysteine protease inhibitors with antiparasitic activity

Bioorg Med Chem Lett. 2010 Sep 15;20(18):5541-3. doi: 10.1016/j.bmcl.2010.07.062. Epub 2010 Aug 6.

Authors

Thilo Waag¹, Christoph Gelhaus, Jennifer Rath, August Stich, Matthias Leippe, Tanja Schirmeister

Affiliation

¹ Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.

PMID: 20692829
DOI: 10.1016/j.bmcl.2010.07.062

Abstract

Allicin and derivatives thereof inhibit the CAC1 cysteine proteases falcipain 2, rhodesain, cathepsin B and L in the low micromolar range. The structure-activity relationship revealed that only derivatives with primary carbon atom in vicinity to the thiosulfinate sulfur atom attacked by the active-site Cys residue are active against the target enzymes. Some compounds also show potent antiparasitic activity against Plasmodium falciparum and Trypanosoma brucei brucei.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiparasitic Agents / chemistry*
Antiparasitic Agents / pharmacology*
Cysteine Endopeptidases / metabolism
Cysteine Proteinase Inhibitors / chemistry*
Cysteine Proteinase Inhibitors / pharmacology*
Disulfides
Garlic / chemistry
Humans
Malaria, Falciparum / drug therapy
Plasmodium falciparum / drug effects
Plasmodium falciparum / enzymology*
Sulfinic Acids / chemistry*
Sulfinic Acids / pharmacology*
Trypanosoma brucei brucei / drug effects
Trypanosoma brucei brucei / enzymology*
Trypanosomiasis, African / drug therapy

Substances

Antiparasitic Agents
Cysteine Proteinase Inhibitors
Disulfides
Sulfinic Acids
allicin
Cysteine Endopeptidases