Synthesis of ethyl 7-hydroxy-1-azacoumarin-3-carboxylate (3) was developed using ethyl-7-hydroxy coumarin-3-carboxylate and ammonium solution as the key synthons. Condensation of ethyl 7-hydroxy-1-azacoumarin-3-carboxylate with ammonium acetate and aniline to give N-substituted-7-hydroxy-1-azacoumarin-3-carboxamides (7-Hydroxy -1-azacoumarin-3-carboxamide (4) and N-phenyl 7-Hydroxy-1-azacoumarin-3-carboxamide (5)). Bromo derivative (N-phenyl 6, 8-dibromo-7-hydroxy-1-azacoumarin-3-carboxamide (6)) was obtained from halogenation of compound N-phenyl 7-Hydroxy-1-azacoumarin-3-carboxamide (5) with bromine in glacial acetic acid. N-phenyl-2,5-diacetoxy-6, 8-disubstituted-Quinoline-3-carboxamides (N-phenyl 2,7-diacetoxy-Quinoline-3-carboxamide (7) and N-phenyl 2,7-diacetoxy-6,8-dibromo-Quinoline-3-carboxamide (8)) were prepared via the acetylation of compounds 5 and 6 with acetic anhydride. Five compounds 4–8 were evaluated in vitro against more than one human tumor cell lines. Among the selected compounds, 6 showed the best in vitro cytotoxicity against the human cancer cell line; MCF-7 (with IC50 = 10.12 μM). In addition, cell cycle analysis of compound 6 demonstrated cell cycle arrest at G2/M phase and Pre-G1 apoptosis.
