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Type: Artigo
Title: Synthesis, biological evaluation, and structure-activity relationships of potent noncovalent and nonpeptidic cruzain Inhibitors as anti-trypanosoma cruzi agents
Author: Ferreira, R. S.
Oliva, G.
Dessoy, M. A.
Sales, A. I. L.
Krogh, R.
Pauli, I.
Andricopulo, A. D.
Dias, L. C.
Souza, M. L.
Abstract: The development of cruzain inhibitors has been driven by the urgent need to develop novel and more effective drugs for the treatment of Chagas' disease. Herein, we report the lead optimization of a class of noncovalent cruzain inhibitors, starting from an inhibitor previously cocrystallized with the enzyme (K-i = 0.8 mu M). With the goal of achieving a better understanding of the structure-activity relationships, we have synthesized and evaluated a series of over 40 analogues, leading to the development of a very promising competitive inhibitor (8r, IC50 = 200 nM, K-i = 82 nM). Investigation of the in vitro trypanocidal activity and preliminary cytotoxicity revealed the potential of the most potent cruzain inhibitors in guiding further medicinal chemistry efforts to develop drug candidates for Chagas' disease
Subject: Doença de Chagas
Invasão celular
Country: Estados Unidos
Editor: American Chemical Society
Rights: Aberto
Identifier DOI: 10.1021/jm401709b
Date Issue: 2014
Appears in Collections:IQ - Artigos e Outros Documentos

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