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

Author(s)

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

• Document type: Journal article
• Source: Bioorganic & Medicinal Chemistry; v. 25, n. 17, p. 4620-4627, SEP 1 2017.
• Web of Science Citations: 5

Abstract

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. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 14/50249-8 - Green chemistry: sustainable synthetic methods employing benign solvents, safer reagents, and bio-renewable feedstock
• Grantee: Arlene Gonçalves Corrêa
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC