New non-peptidic Inhibitors of Papain Derived from Etacrynic Acid

Title: New non-peptidic Inhibitors of Papain Derived from Etacrynic Acid

Volume: 1 Issue: 4

Author(s): U. Kaeppler and T. Schirmeister

Affiliation:

Keywords: cysteine protease inhibitor, michael addition, papain, etacrynic acid

Abstract: Cysteine proteases are connected to various viral and parasitic infections, as well as to other severe diseases like arthritis, stroke and cancer. Due to its α,β-unsaturated carbonyl moiety etacrynic acid, a well known diuretic, can inhibit cysteine proteases in a Michael-type reaction by reaction with the nucleophilic cysteine residue of the active site. For first structure-activity-relationship studies modifications at various positions of the etacrynic acid structure have been investigated concerning inhibition potency against the CAC1 protease papain: length of the side chain, substitution pattern of the aromatic ring as well as influence and necessity of acidic groups, esters or amides. Additionally, the effect of the aromatic ring was evaluated by replacement with a cyclohexyl moiety.

Cite this article as:

Kaeppler U. and Schirmeister T., New non-peptidic Inhibitors of Papain Derived from Etacrynic Acid, Medicinal Chemistry 2005; 1 (4) . https://dx.doi.org/10.2174/1573406054368701