Discovery of a new isomannide-based peptidomimetic synthetized by Ugi multicomponent reaction as human tissue kallikrein 1 inhibitor

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Barros, Thalita G. ; Santos, Jorge A. N. ; de Souza, Bruno E. G. ; Sodero, Ana Carolina R. ; de Souza, Alessandra M. T. ; da Silva, Dayane P. ; Rodrigues, Carlos Rangel ; Pinheiro, Sergio ; Dias, Luiza R. S. ; Abrahim-Vieira, Barbara ; Puzer, Luciano ; Muri, Estela M. F.

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry Letters; v. 27, n. 2, p. 314-318, JAN 15 2017.
• Citações Web of Science: 4

Resumo

Human kallikrein 1 (KLK1) is the most extensively studied member of this family and plays a major role in inflammation processes. From Ugi multicomponent reactions, isomannide-based peptidomimetic 10 and 13 where synthesized and showed low micromolar values of IC50 for KLK1 The most active compound (10) presented competitive mechanism, with three structural modifications important to interact with active site residues which corroborates its KLK1 inhibition. Finally, the most active compound also showed good ADMET profile, which indicates compound 10 as a potential hit in the search for new KLK1 inhibitors with low side effects. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 13/10548-3 - Desenvolvimento de serpinas mutantes para inibição de calicreínas teciduais humanas
• Beneficiário: Luciano Puzer
• Modalidade de apoio: Auxílio à Pesquisa - Regular