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Title: Design, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi.
Authors: Coelho, Gleicekelly Silva
Andrade, Josimara Souza
Xavier, Viviane Flores
Sales Júnior, Policarpo Ademar
Araújo, Bárbara Caroline Rodrigues de
Fonseca, Kátia da Silva
Caetano, Melissa Soares
Murta, Silvane Maria Fonseca
Vieira, Paula Melo de Abreu
Carneiro, Cláudia Martins
Taylor, Jason Guy
Keywords: Chagas disease
In silico
Triosephosphate isomerase
Issue Date: 2019
Citation: COELHO, G. S. et al. Design, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi. Chemical Biology & Drug Design, v. 93, p. 337-335, mar. 2019. Disponível em: <>. Acesso em: 21 fev. 2019.
Abstract: Chagas disease is caused by infection with the parasite protozoan Trypanosoma cruzi and affects about 8 million people in 21 countries in Latin America. The main form of treatment of this disease is still based on the use of two drugs, benznidazole and nifurtimox, which both present low cure rates in the chronic phase and often have serious side-effects. Herein, we describe the synthesis of tricyclic coumarins that were obtained via NHC organocatalysis and evaluation of their trypanocidal activity. Molecular docking studies against trypanosomal enzyme triosephosphate isomerase (TIM) were carried out, as well as a theoretical study of the physicochemical parameters. The tricyclic coumarins were tested in vitro against the intracellular forms of Trypanosoma cruzi. Among the 18 compounds tested, 10 were more active than the reference drug benznidazole. The trypanocidal activity of the lead compound was rationalized by molecular docking study which suggested the strong interaction with the enzyme TIM by T. cruzi and therefore indicating a possible mode of action. Furthermore, the selectivity index of eight tricyclic coumarins with high anti-T. cruzi activity was above 50 and thus showing that these lead compounds are viable candidates for further in vivo assays.
ISSN: 17470285
Appears in Collections:DEACL - Artigos publicados em periódicos

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