Author(s)

Ali Bouattour¹, Mehdi Fakhfakh¹, Souhir Abid^1,2, Ludovic Paquin^3,4, Rémy Le Guével⁵, Thierry Charlier⁵, Sandrine Ruchaud⁶, Stéphane Bach⁶, Jean-Pierre Bazureau^3,4*, Houcine Ammar¹

¹Laboratoire de Chimie Appliquée: Hétérocycles, Corps Gras et Polymères, Faculté des Sciences de Sfax, Université de Sfax, Sfax, Tunisie.
²Département de Chimie, Collège des Sciences et des Arts, Université de Jouf, Al Qurayyat, KSA.
³Institut des Sciences Chimiques de Rennes (ISCR), UMR CNRS 6226, Université de Rennes 1, Campus de Beaulieu, Rennes, France.
⁴S2 Wave Platform, ScanMAT UMS 2001CNRS, Université de Rennes 1, Campus de Beaulieu, Rennes, France.
⁵Université de Rennes 1, ImPACcell Platform, Campus Villejean, Rennes, France.
⁶Sorbonne Universités, UPMC Université Paris 06, CNRS USR3151, Protein Phosphorylation and Human Disease Unit, KISSf Platform, Station Biologique, Place Georges Teissier, Roscoff, France.

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).

Iminocoumarin, 2H-[1]benzopyran, 2-Imino-2H-[1]benzopyran, 4H-chromene, 2-Amino-4H-chromene, Nitrogen/Nitrogen Displacement, Protein Kinase Inhibition, Cytotoxicity

Bouattour, A. , Fakhfakh, M. , Abid, S. , Paquin, L. , Guével, R. , Charlier, T. , Ruchaud, S. , Bach, S. , Bazureau, J. and Ammar, H. (2020) 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, 10, 88-103. doi: 10.4236/ijoc.2020.102006.