Asymmetric synthesis and evaluation of epoxy-α-acyloxycarboxamides as selective inhibitors of cathepsin L


dos Santos, Deborah A.1 ; Deobald, Anna Maria1 ; Cornelio, Vivian E.1 ; Avila, Roberta M. D.1 ; Cornea, Renata C.2 ; Bernasconi, Gilberto C. R.2 ; Paixao, Marcio W.1 ; Vieira, Paulo C.1 ; Correa, Arlene G.1


Cathepsin L plays important roles in physiological processes as well as in the development of many pathologies. Recently the attentions were turned to its association with tumor progress what makes essential the development of more potent and selective inhibitors. In this work, epoxipeptidomimetics were investigated as new cathepsin inhibitors. This class of compounds is straightforward obtained by using a green one-pot asymmetric epoxidation/Passerini 3-MCR. A small library of 17 compounds was evaluated against cathepsin L, and among them LSPN423 showed to be the most potent. Investigations of the mechanism suggested a tight binding uncompetitive inhibition.

1  Centre of Excellence for Research in Sustainable Chemistry – CERSusChem, Department of Chemistry, Federal University of São Carlos, São Carlos, SP, Brazil

2  Advanced Centre for Study and Research – Campinas, SP, Brazil

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