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

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)65153-65166
Number of pages14
JournalRSC Advances
Volume5
Issue number80
DOIs
Publication statusPublished - 22 Jul 2015

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Chemistry(all)

Fingerprint

Dive into the research topics of 'New aryloxy-quinone derivatives as potential anti-Chagasic agents: synthesis, trypanosomicidal activity, electrochemical properties, pharmacophore elucidation and 3D-QSAR analysis'. Together they form a unique fingerprint.

Cite this