p-Toluenesulfonic acid mediated one-pot cascade synthesis and cytotoxicity evaluation of polyfluorinated 2-aryl-2,3-dihydroquinolin-4-ones and their derivatives

Abstract Biologically interesting polyfluorinated 2-aryl-2,3-dihydroquinolin-4-ones ( 5 ), 3-benzylidene-2-aryl-2,3-dihydroquinolin-4-ones ( 6 ) and 7-methyl-6-aryl-5,6-dihydrodibenzo[ b,h ][1,6] naphthyridines ( 7 ) were synthesized using a mild and efficient one-pot procedure starting from 2-aminoacetophenones and trifluorobenzaldehyde in the presence of p -toluenesulfonic acid. Thanks to the use of a high-active polyfluorinated electrophile this synthetic protocol provides rapid access to a variety of bioactive heterocyclic assemblies. Screening of the synthesized compounds for their cytotoxic activity against human tumor cell lines, including breast cancer (MCF-7), lung carcinoma (A-549), and myeloma cancer cells (RPMI 8226) revealed that polyfluorinated compounds 6b–f showed manifest cytotoxic effects (with IC 50  = 2.5 ÷ 7 μM for MCF-7 and RPMI 8226 cancer cells).