Synthesis and biological evaluation of reversible inhibitors of IdeS, a bacterial cysteine protease and virulence determinant

Analogues of the irreversible protease inhibitors TPCK and TLCK have been synthesized and tested as inhibitors of the bacterial cysteine protease IdeS excreted by Streptococcuspyogenes. Eight compounds were identified as inhibitors of IdeS in an in vitro assay. The most potent compounds contained an aldehyde function, thus acting as efficient reversible inhibitors, nitrile and azide derivatives showed moderate activity.

Potential inhibitors of the bacterial cysteine protease IdeS were synthesized and tested. Derivatives with azide, nitrile and aldehyde functionalities showed moderate to high inhibitory activity.Figure optionsDownload as PowerPoint slide