Synthesis of New 2-Phenylamino-4H-chromene-3-carbonitrile Derivatives and Their Effects on Tumor Cell Lines and against Protein Kinases

Ali Bouattour (1) , Mehdi Fakhfakh (1) , Souhir Abid (1) , Ludovic Paquin (2, 3) , Rémy Le Guével (4) , Thierry D Charlier (4) , Sandrine Ruchaud (5) , Stéphane Bach (5) , Jean-Pierre Bazureau (2, 3) , Houcine Ammar (1, 4)

1 Université de Sfax - University of Sfax
2 ISCR - Institut des Sciences Chimiques de Rennes
3 ScanMAT - Synthèse Caractérisation Analyse de la Matière
4 ImPACcell - Plate-forme ImPACcell
5 LBI2M - Laboratoire de Biologie Intégrative des Modèles Marins

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).

Mots clés: Iminocoumarin; 2H-[1]benzopyran; 2-Imino-2H-[1]benzopyran; 4H-chromene; 2-Amino-4H-chromene; Nitrogen/Nitrogen Displacement; Protein Kinase Inhibition; Cytotoxicity

Domaines: Sciences du Vivant [q-bio]; Chimie

Ali Bouattour, Mehdi Fakhfakh, Souhir Abid, Ludovic Paquin, Rémy Le Guével, et al.. Synthesis of New 2-Phenylamino-4H-chromene-3-carbonitrile Derivatives and Their Effects on Tumor Cell Lines and against Protein Kinases. International Journal of Organic Chemistry, 2020, 10 (02), pp.88-103. ⟨10.4236/ijoc.2020.102006⟩. ⟨hal-03869130v1⟩