Sassatelli Mathieu, Bouchikhi Fadoua, Aboab Bettina, Anizon Fabrice, Fabbro Doriano, Prudhomme Michelle, Moreau Pascale
Laboratoire SEESIB, Université Blaise Pascal, UMR 6504 du CNRS, Aubière, France.
Anticancer Drugs. 2007 Oct;18(9):1069-74. doi: 10.1097/CAD.0b013e328182d281.
In the course of studies on the preparation of potential kinase inhibitors, we were interested in the synthesis of diversely substituted glycosyl-isoindigo derivatives. To get an insight into the effect of the substitution pattern of the isoindigo aromatic and carbohydrate moieties on the biological activities and to identify the cellular target(s) involved in the in-vitro antiproliferative activity of these derivatives, their inhibitory activities toward a panel of 10 different kinases were examined. The best inhibitory activities were found toward cyclin-dependent kinase 2/cyclin A. Molecular modelling experiments were carried out to investigate the binding interactions between the active site of cyclin-dependent kinase 2 and the lead compound of this series.
在对潜在激酶抑制剂制备的研究过程中，我们对多种取代的糖基异靛蓝衍生物的合成感兴趣。为了深入了解异靛蓝芳香族和碳水化合物部分的取代模式对生物活性的影响，并确定这些衍生物体外抗增殖活性所涉及的细胞靶点，我们检测了它们对一组10种不同激酶的抑制活性。发现对细胞周期蛋白依赖性激酶2/细胞周期蛋白A具有最佳抑制活性。进行了分子模拟实验，以研究细胞周期蛋白依赖性激酶2的活性位点与该系列先导化合物之间的结合相互作用。
