Vinyl Sulfone Containing Parasitic Cysteinyl Protease Inhibitors

Elizabeth      Dunny; Paul      Evans

doi:10.2174/157340711798375859

Abstract

Cysteine proteases are important therapeutic targets for numerous disease states including arthritis, osteoporosis, African sleeping sickness and Chagas disease. They have been shown to be viable drug targets for parasitic diseases through in vitro and animal model studies. This review examines the development of vinyl sulfone containing cysteine protease inhibitors. Peptidyl vinyl sulfones are superior inhibitors as they comprise the reactive vinyl sulfone warhead in addition to the peptide backbone, which has complementarity with the enzyme active site. The design, synthesis and activity of these protease inhibitors are discussed. Additionally, different methods for the preparation of vinyl sulfones are presented.

Keywords: Cruzain, cysteine proteases, parasitic inhibiotrs, peptides, rhodesain, vinyl sulfones, therapeutics targets, drug targets, parasitic diseases, metalloproteases