RESUMEN

In this study the rational design, synthesis, and anticancer activity of quinoline-derived trifluoromethyl alcohols were evaluated. Members of this novel class of trifluoromethyl alcohols were identified as potent growth inhibitors in a zebrafish embryo model. Synthesis of these compounds was carried out with an sp(3) -C-H functionalization strategy of methyl quinolines with trifluoromethyl ketones. A zebrafish embryo model was also used to explore the toxicity of ethyl 4,4,4-trifluoro-3-hydroxy-3-(quinolin-2-ylmethyl)butanoate (1), 2-benzyl-1,1,1-trifluoro-3-(quinolin-2-yl)propan-2-ol (2), and trifluoro-3-(isoquinolin-1-yl)-2-(thiophen-2-yl)propan-2-ol (3). Compounds 2 and 3 were found to be more toxic than compound 1; apoptotic staining assays indicated that compound 3 causes increased cell death. In vitro cell proliferation assays showed that compound 2, with an LC50 value of 14.14 µm, has more potent anticancer activity than cisplatin. This novel class of inhibitors provides a new direction in the discovery of effective anticancer agents.

Asunto(s)

Alcoholes/farmacología , Antineoplásicos/farmacología , Descubrimiento de Drogas , Hidrocarburos Fluorados/farmacología , Quinolinas/farmacología , Quinolinas/toxicidad , Pez Cebra/embriología , Alcoholes/síntesis química , Alcoholes/química , Alcoholes/toxicidad , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/toxicidad , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Hidrocarburos Fluorados/síntesis química , Hidrocarburos Fluorados/química , Hidrocarburos Fluorados/toxicidad , Modelos Animales , Estructura Molecular , Quinolinas/química , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de Xenoinjerto

Asunto(s)

Humanos , Artritis/diagnóstico