Copper-Catalyzed Multicomponent Reaction to Construct Fluorinated Indole-quinoxalin-2(1H)-ones and Their Biological Evaluation

A practical and mild three-component reaction of indoles, quinoxalin-2(1H)-ones, and CF3SO2Na is disclosed for the facile access of various 3-[2-(trifluoromethyl)1H-indol-3-yl]quinoxalin-2(1H)-ones using low-cost and catalytic amount of CuF2 as the catalyst. This strategy exhibits high site-selectivity, step economy, and broad substrates scope. Synthetic utility was demonstrated by the one-pot two-step synthesis of N-alkyl triazoles compounds via a click chemistry. To evaluate the antiproliferative activity of these compounds, A549 s (human lung adenocarcinoma cells) and HUVECs, as a model of toxicity, were used in MTT assay. The outcomes disclosed for 6-CO2Me and a N-alkyl triazole derivatives were of potent antiproliferative effect against A549 s (IC50 = 4.7 and 14.9 mu M, respectively) with slight cytotoxicity in HUVECs. Morphological study was conducted by AO/EB dual staining, indicated hydrochloride 6-CO2Me derivative was capable of inducing apoptosis of A549 cells.

Automated summary

A practical and mild three-component reaction for the synthesis of various indole derivatives was developed. This method demonstrated high site-selectivity, step economy, and broad substrate scope. The synthetic utility of this approach was demonstrated by the synthesis of N-alkyl triazole compounds via a one-pot two-step click chemistry. Evaluation of the antiproliferative activity of these compounds revealed potent effects against lung adenocarcinoma cells with minimal cytotoxicity to normal cells.