RESUMO

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.

Assuntos

Amidas/química , Catepsina L/antagonistas & inibidores , Inibidores de Cisteína Proteinase/síntese química , Amidas/metabolismo , Amidas/farmacologia , Animais , Antiparasitários/química , Antiparasitários/metabolismo , Antiparasitários/farmacologia , Catepsina L/metabolismo , Inibidores de Cisteína Proteinase/metabolismo , Inibidores de Cisteína Proteinase/farmacologia , Concentração Inibidora 50 , Parasitos/efeitos dos fármacos , Parasitos/enzimologia , Estereoisomerismo , Relação Estrutura-Atividade