title: Synthesis and trypanocidal activity of a library of 4-substituted 2-(1H-pyrrolo[3,2-c]pyridin-2-yl)propan-2-ols.
abstract: 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.
authors.affiliation: Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Balfour
authors.affiliation: Laboratório Nacional de Biociências (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, SP, Brazil.
authors.forename: Caio H
authors.initials: CH
authors.lastname: Franco
authors.affiliation: Laboratório Nacional de Biociências (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, SP, Brazil.
authors.forename: Carolina B
authors.initials: CB
authors.lastname: Moraes
authors.affiliation: Laboratório Nacional de Biociências (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, SP, Brazil. Electronic address: luciofreitasjunior@gmail.com.
authors.forename: Lucio H
authors.initials: LH
authors.lastname: Freitas-Junior
authors.affiliation: Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: hstefani@usp.br.
authors.forename: Hélio A
authors.initials: HA
authors.lastname: Stefani
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: C000617224:2-(4-(2-fluoro-(1,1'-biphenyl)-4-yl)-1H-pyrrolo(3,2-c)pyridin-2-yl)propan-2-ol; C000617223:2-(4-(4-(ethylthio)phenyl)-1H-pyrrolo(3,2-c)pyridin-2-yl)propan-2-ol; D009593:Nitroimidazoles; D011725:Pyridines; D011758:Pyrroles; D014344:Trypanocidal Agents; C475261:pyrrolo(3,2-c)pyridine; C009999:benzonidazole
keywords: 5-Endo-dig; Chagas disease; Sonogashira; Suzuki-Miyaura; Trypanosoma