Heteroaromatization of Coumarin Part III: One-Pot Synthesis, Antitumor Activity, DFT Studies, and Molecular Docking of Coumarin Derivatives

: A one-pot three/two-component reaction of 3-acetyl-coumarin (1), 4/3-anisaldehyde (2a,b) and malononitrile or 3-acetylcoumarin (1) and 2-(4/3-methoxybenzylidene)malononitrile (5a,b) in glacial acetic acid/ammonium acetate under reflux afforded 2-amino-4-(4/3-methoxyphenyl)-6-(2-oxo-2H-chromen-3- yl)nicotinonitrile (4a,b). Spectral data helped establish the structures of the compounds. Subsequently, an antiproliferative evaluation against a selected line of tumorous cells (HepG-2, MDA-MB-231 and A549) was performed in-vitro for the novel 2-amino-4-(4/3-methoxyphenyl)-6-(2-oxo-2H-chromen-3-yl)nicotinonitrile (4a,b). Compound 4a exhibited good efficiency against the MDA-MB-231 and A549 cell lines compared with the reference drug (Vinblastine). Furthermore, the chemical reactivity of both compounds was discussed using DFT. Lastly, a molecular docking analysis was addressed and conducted for these desired molecules.