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RUTHENIUM(II)- AND PALLADIUM(II)-CATALYZED POSITION-DIVERGENT C–H OXYGENATIONS OF ARYLATED QUINONES: IDENTIFICATION OF HYDROXYLATED QUINONOID COMPOUNDS WITH POTENT TRYPANOCIDAL ACTIVITY
Gontijo, Talita B. et al. | Date Issued: 2021
Author
Gontijo, Talita B.
Carvalho, Renato L. de
Pereira, Luiza Dantas
Menna-Barreto, Rubem F. S.
Rogge, Torben
Ackermann, Lutz
Silva Junior, Eufrânio N. da
Affilliation
Institut für Organische und Biomolekulare Chemie, Georg-August-Universit¨at Göttingen. Tammannstraße 2, 37077 Göttingen, Germany / Universidade Federal de Minas Gerais. Departamento de Química. Instituto de Ciências Exatas. Belo Horizonte, MG, Brasil.
Institut für Organische und Biomolekulare Chemie, Georg-August-Universit¨at Göttingen. Tammannstraße 2, 37077 Göttingen, Germany / Universidade Federal de Minas Gerais. Departamento de Química. Instituto de Ciências Exatas. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen. Tammannstraße 2, 37077 Göttingen, Germany.
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen. Tammannstraße 2, 37077 Göttingen, Germany / DZHK (German Center for Cardiovascular Research). Potsdamer Strasse 58, 10785 Berlin, Germany.
Universidade Federal de Minas Gerais. Departamento de Química. Instituto de Ciências Exatas. Belo Horizonte, MG, Brasil.
Abstract
A diversity-oriented synthesis of hydroxylated aryl-quinones via C–H oxygenation reactions and their evaluation against Trypanosoma cruzi, the etiological agent of Chagas disease, was accomplished. With the use of ruthenium (II)- or palladium(II)-based catalysts, complementary regioselectivities were observed in the hydroxylation reactions and we have identified 9 compounds more potent than benznidazole (Bz) among these novel arylated and hydroxylated quinones. For instance, 5-hydroxy-2-[4-(trifluoromethyl)phenyl]-1,4-naphthoquinone (4h) with an IC50/24 h value of 22.8 μM is 4.5-fold more active than the state-of-the-art drug Bz. This article provides the first example of the application of C–H activation for the position-selective hydroxylation of arylated quinones and the identification of these compounds as trypanocidal drug candidates.
Keywords in Portuguese
Quinones
Doença de Chagas
Ruthenium
Palladium
Oxigenação C – H
 
Keywords
Quinones
Chagas disease
Ruthenium
Palladium
C–H Oxygenation
 
Publisher
Elsevier
Citation
GONTIJO, Talita B. et al. Ruthenium(II)- and Palladium(II)-catalyzed position-divergent C–H oxygenations of arylated quinones: Identification of hydroxylated quinonoid compounds with potent trypanocidal activity. Bioorganic & Medicinal Chemistry, v. 40, 116164, p. 1 -11, Apr. 2021.
DOI
10.1016/j.bmc.2021.116164
ISSN
0968-0896