Anti-breast cancer activity of some novel quinoline derivatives

Abstract

To discover new bioactive lead compounds for medicinal purposes, 2-cyano-3-(4-substituted)-[N]-(quinolin-3-yl) acrylamide derivatives 2-24, chromenes 25, 26 and benzochromenes 27, 28 were synthesized. The structures of the newly synthesized compounds were confirmed by elemental analyses, IR, [1]H NMR and [13]C NMR spectroscopies. In addition, the structure of compound 1 was confirmed through X-ray crystallography. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. The corresponding 2-cyano-3-(4-hydroxy-3-methoxyphenyl)-[N]-(quinolin-3-yl) acrylamide (15), 3-oxo-[N]-(quinolin-3-yl)-3[H]-benzol[[f]] chromene-2-carboxamide (27), 2-cyano-3-(4-fluorophenyl-[N]-(quinolin-3-yl) acrylamide (7), 2-cyano-5-(4-(dimethyl-amino) phenyl)-[N]-(quinolin-3-yl) penta-2,4-dienamide (19) exhibited higher activity compared to doxorubicin (with [IC][50] value of 47.9 μmol L[-1]) as a reference drug, with [IC][50] values of 29.8, 39.0, 40.0, 40.4 μmol L[-1], resp. Also, quinoline acrylamides containing 2,3,4-trimethoxyphenyl 17, 2-chlorophenyl 10, benzo[[d]][1,3]dioxol 12, 2-methoxynaphthalen 22, 2,4-dichlorophenyl 18 and quinoline carrying a chromene-3-carboxamide moiety 25 were nearly as active as doxorubicin, while quinoline acrylamides incorporating unsubstituted phenyl 2, [p]-tolyl 3, 2,4-dienamide 8, 3-nitrophenyl 13, 4-nitrophenyl 14, 3,4-dimethoxyphenyl 16 and chromene 26 exhibited a moderate activity. In addition, quinoline with acetamide 1, 4-hydroxyphenyl 4, 4-dimethylaminophenyl 9, 4-chlorophenyl 11, 3-bromophenyl 20, 4-bromophenyl 21 and 3-thienyl moiety 24 showed less activity than doxorubicin. On the other hand, quinoline having 2-methoxyphenyl 5, 4-methoxyphenyl 6, 4-metho xynaphthalene 23 and chromene-2-carboxamide 28 showed no activity.