摘要
The synthesis of 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6(a-d)</strong> 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 <strong>1</strong> and propanedinitrile <strong>2</strong> which produced 2-iminocoumarin <strong>3</strong> which was submitted to nitrogen/nitrogen displacement in the presence of aromatic primary amine <strong>4</strong>. In the third step, reduction of <strong>5</strong> led to the desired 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6</strong>. Compounds <strong>5(a-d)</strong> and <strong>6(a-d)</strong> were evaluated for their potential <em>in vitro</em> 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 <strong>5c</strong> and <strong>6b</strong> exhibited inhibition on HsCK1e (<strong>5c</strong>: 44% and <strong>6b</strong>: 42% at 1 μM) and <strong>5c </strong>for cytotoxicity on PC3 cell lines (63% at 25 μM).
The synthesis of 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6(a-d)</strong> 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 <strong>1</strong> and propanedinitrile <strong>2</strong> which produced 2-iminocoumarin <strong>3</strong> which was submitted to nitrogen/nitrogen displacement in the presence of aromatic primary amine <strong>4</strong>. In the third step, reduction of <strong>5</strong> led to the desired 2-phenylimino-4<em>H</em>-chromene-3-carbonitriles <strong>6</strong>. Compounds <strong>5(a-d)</strong> and <strong>6(a-d)</strong> were evaluated for their potential <em>in vitro</em> 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 <strong>5c</strong> and <strong>6b</strong> exhibited inhibition on HsCK1e (<strong>5c</strong>: 44% and <strong>6b</strong>: 42% at 1 μM) and <strong>5c </strong>for cytotoxicity on PC3 cell lines (63% at 25 μM).
作者
Ali Bouattour
Mehdi Fakhfakh
Souhir Abid
Ludovic Paquin
Rémy Le Guével
Thierry Charlier
Sandrine Ruchaud
Stéphane Bach
Jean-Pierre Bazureau
Houcine Ammar
Ali Bouattour;Mehdi Fakhfakh;Souhir Abid;Ludovic Paquin;Rémy Le Guével;Thierry Charlier;Sandrine Ruchaud;Stéphane Bach;Jean-Pierre Bazureau;Houcine Ammar(Laboratoire de Chimie Appliquée: Hétérocycles, Corps Gras et Polymères, Faculté des Sciences de Sfax, Université de Sfax, Sfax, Tunisie;Département de Chimie, Collège des Sciences et des Arts, Université de Jouf, Al Qurayyat, KSA;Institut des Sciences Chimiques de Rennes (ISCR), UMR CNRS 6226, Université de Rennes 1, Campus de Beaulieu, Rennes, France;S2 Wave Platform, ScanMAT UMS 2001CNRS, Université de Rennes 1, Campus de Beaulieu, Rennes, France;Université de Rennes 1, ImPACcell Platform, Campus Villejean, Rennes, France;Sorbonne Universités, UPMC Université Paris 06, CNRS USR3151, Protein Phosphorylation and Human Disease Unit, KISSf Platform, Station Biologique, Place Georges Teissier, Roscoff, France)
