Design, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi.

Simple item page
dc.contributor.authorCoelho, Gleicekelly Silva
dc.contributor.authorAndrade, Josimara Souza
dc.contributor.authorXavier, Viviane Flores
dc.contributor.authorSales Júnior, Policarpo Ademar
dc.contributor.authorAraújo, Bárbara Caroline Rodrigues de
dc.contributor.authorFonseca, Kátia da Silva
dc.contributor.authorCaetano, Melissa Soares
dc.contributor.authorMurta, Silvane Maria Fonseca
dc.contributor.authorVieira, Paula Melo de Abreu
dc.contributor.authorCarneiro, Cláudia Martins
dc.contributor.authorTaylor, Jason Guy
dc.date.accessioned2019-03-27T16:36:25Z
dc.date.available2019-03-27T16:36:25Z
dc.date.issued2019
dc.description.abstractChagas 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.pt_BR
dc.identifier.citationCOELHO, 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: <https://onlinelibrary.wiley.com/doi/full/10.1111/cbdd.13420>. Acesso em: 21 fev. 2019.pt_BR
dc.identifier.issn17470285
dc.identifier.urihttp://www.repositorio.ufop.br/handle/123456789/10838
dc.identifier.uri2https://onlinelibrary.wiley.com/doi/full/10.1111/cbdd.13420pt_BR
dc.language.isoen_USpt_BR
dc.rightsrestritopt_BR
dc.subjectChagas diseasept_BR
dc.subjectIn silicopt_BR
dc.subjectIsocoumarinspt_BR
dc.subjectOrganocatalysispt_BR
dc.subjectTriosephosphate isomerasept_BR
dc.titleDesign, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi.pt_BR
dc.typeArtigo publicado em periodicopt_BR
Files
Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
ARTIGO_DesignSynthesisMolecular.pdf
Size:
1.27 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
924 B
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
DEACL - Artigos publicados em periódicos