TITLE:
Synthesis of New 2-Phenylamino-4H-chromene-3-carbonitrile Derivatives and Their Effects on Tumor Cell Lines and against Protein Kinases
AUTHORS:
Ali Bouattour, Mehdi Fakhfakh, Souhir Abid, Ludovic Paquin, Rémy Le Guével, Thierry Charlier, Sandrine Ruchaud, Stéphane Bach, Jean-Pierre Bazureau, Houcine Ammar
KEYWORDS:
Iminocoumarin, 2H-[1]benzopyran, 2-Imino-2H-[1]benzopyran, 4H-chromene, 2-Amino-4H-chromene, Nitrogen/Nitrogen Displacement, Protein Kinase Inhibition, Cytotoxicity
JOURNAL NAME:
International Journal of Organic Chemistry,
Vol.10 No.2,
June
30,
2020
ABSTRACT: The synthesis of 2-phenylimino-4H-chromene-3-carbonitriles 6(a-d) in good overall yields using an efficient and practical methodology in 3 steps has been implemented in this present work. The first step was a heterocyclization between 2-hydroxybenzaldehyde 1 and propanedinitrile 2 which produced 2-iminocoumarin 3 which was submitted to nitrogen/nitrogen displacement in the presence of aromatic primary amine 4. In the third step, reduction of 5 led to the desired 2-phenylimino-4H-chromene-3-carbonitriles 6. Compounds 5(a-d) and 6(a-d) were evaluated for their potential in vitro cytotoxicity against six selected tumor cell lines (Huh7-D12, Caco2, MDA-MB231, HCT 116, PC3 and NCI-H727) and tested for their protein kinase inhibition on eight selected protein kinases. Among them, compounds 5c and 6b exhibited inhibition on HsCK1e (5c: 44% and 6b: 42% at 1 μM) and 5c for cytotoxicity on PC3 cell lines (63% at 25 μM).