Cysteine proteases belonging to the papain superfamily have been recognized as interesting therapeutic targets for the search for new drugs against infectious tropical diseases such as malaria (falcipain), Chagas’ disease (curtain), leishmaniasis, and Sleeping sickness (rhodesian), and a number of human pathologies, including cancer, Alzheimer’s disease, and osteoporosis (cathepsins). We have reported irreversible inhibitors Dipeptidyl epoxyesters (kinac/KI up to 92,090 M−1/s−1) [1], Dipeptidyl enoates (kinac/KI up to 1,530,000 M−1/s−1) [2,3], Aminoacyl epoxysulfones [4], and also reversible inhibitors Dipeptidyl nitroalkenes (IC50 up to 0.44 nM) [5] as inhibitors of parasitic cysteine proteases and cathepsins. Inhibition kinetics and computational studies have been used to study the mode of action of these inhibitors.
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