New aryloxy-quinone derivatives as potential anti-Chagasic agents: synthesis, trypanosomicidal activity, electrochemical properties, pharmacophore elucidation and 3D-QSAR analysis

Karina Vázquez, Christian Espinosa-Bustos, Jorge Soto-Delgado, Ricardo A. Tapia, Javier Varela, Estefanía Birriel, Rodrigo Segura, Jaime Pizarro, Hugo Cerecetto, Mercedes González, Margot Paulino, Cristian O. Salas

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

23 Citas (Scopus)

Resumen

A set of new aryloxy-quinones were synthesized and evaluated in vitro against the epimastigote form of Trypanosoma cruzi and their unspecific cytotoxicity was tested on murine macrophages J-774 cells. Most of these novel compounds were found to be much more potent and selective than the standard drug nifurtimox. Interestingly, 2-phenoxy-naphthoquinone 3b displayed a remarkable nanomolar inhibitory activity, IC50 = 20 nM, and a high selectivity index, SI = 625. The Epc1 was determined for the most interesting compounds and no correlation with the trypanosomicidal effect was found. Therefore, an in silico study was carried out to obtain a pharmacophoric model and quantitative structure-trypanosomicidal activity relationship. The designed pharmacophore recognized the more potent and selective molecules, exhibiting five pharmacophoric features. A correlation coefficient R2 of 0.99 of pIC50 plotted against the predicted values indicated that the 3D-QSAR equation could be applied to further predictions of newly designed trypanosomicidal compounds.

Idioma originalInglés
Páginas (desde-hasta)65153-65166
Número de páginas14
PublicaciónRSC Advances
Volumen5
N.º80
DOI
EstadoPublicada - 22 jul. 2015

Áreas temáticas de ASJC Scopus

  • Ingeniería química (todo)
  • Química (todo)

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