Synthesis and trypanocidal activity of a library of 4-substituted 2-(1H-pyrrolo[3,2-c]pyridin-2-yl)propan-2-ols

Autor(es)

Balfour, Michael N. ; Franco, Caio H. ; Moraes, Carolina B. ; Freitas-Junior, Lucio H. ; Stefani, Helio A.

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 128, p. 202-212, MAR 10 2017.
• Citações Web of Science: 4

Resumo

A library of 16 4-substituted 2-(1H-pyrrolo{[}3,2-c]pyridin-2-yl)propan-2-ols 17-32 has been synthesized for use in biological testing against Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. The 4-substituted 2-(1H-pyrrolo{[}3,2-c]pyridin-2-yl)propan-2-ols 17-32 were subjected to biological testing to evaluate their efficacy against intracellular Trypanosoma cruzi (Y strain) amastigotes infecting U2OS human cells, with benznidazole as a reference compound. The assay was performed in duplicate (two independent experiments) and submitted to High Content Analysis (HCA) for determination of trypanocidal activity. Three of the tested compounds presented relatively high trypanocidal activity (19, 22 and 29), however severe host cell toxicity was observed concomitantly. Chemical optimization of the highly active compounds and the synthesis of more compounds for biological testing against Trypanosoma cruzi will be required to improve selectivity and so that a structure-activity relationship can be generated to provide a more insightful analysis of both chemical and biological aspects. (C) 2017 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 12/00424-2 - Síntese de pequenas bibliotecas empregando organotrifluoroboratos de potássio em reações de Suzuki-Miyaura
• Beneficiário: Helio Alexandre Stefani
• Modalidade de apoio: Auxílio à Pesquisa - Temático