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

作者：Vazquez Karina; Espinosa Bustos Christian; Soto Delgado Jorge; Tapia Ricardo A; Varela Javier; Birriel Estefania; Segura Rodrigo; Pizarro Jaime; Cerecetto Hugo; Gonzalez Mercedes; Paulino Margot; Salas Cristian O^*

来源：RSC Advances, 2015, 5(80): 65153-65166.

DOI：10.1039/c5ra10122k

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 E-pc1 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 structuretrypanosomicidal activity relationship. The designed pharmacophore recognized the more potent and selective molecules, exhibiting five pharmacophoric features. A correlation coefficient R-2 of 0.99 of pIC(50) plotted against the predicted values indicated that the 3D-QSAR equation could be applied to further predictions of newly designed trypanosomicidal compounds.

• 出版日期2015
• 单位上海生物信息技术研究中心