Laboratory for Natural Product Chemistry, College of Pharmacy, South Central University for Nationalities, 708 Minyuan Road, Wuhan 430074, China; E-Mails:
Int J Mol Sci. 2010 Sep 28;11(10):3705-24. doi: 10.3390/ijms11103705.
CDK2/cyclin A has appeared as an attractive drug targets over the years with diverse therapeutic potentials. A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. The CoMFA and CoMSIA models, using 38 molecules in the training set, gave r(2) (cv) values of 0.747 and 0.518 and r(2) values of 0.970 and 0.934, respectively. 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained from molecular modeling studies may be helpful to design novel inhibitors of CDK2/cyclin A with desired activity.
CDK2/细胞周期蛋白 A 多年来一直是一个有吸引力的药物靶点，具有多种治疗潜力。对一系列作为有效 CDK2/细胞周期蛋白 A 抑制剂的 4,5-二氢-1H-吡唑并[4,3-h]喹唑啉衍生物进行了基于比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）的计算策略，以及分子对接研究。使用训练集中的 38 个分子的 CoMFA 和 CoMSIA 模型分别给出了 0.747 和 0.518 的 r(2)(cv) 值和 0.970 和 0.934 的 r(2) 值。CoMFA 和 CoMSIA 模型生成的 3D 等高线图用于确定负责生物活性的关键结构要求。应用分子对接探索配体与受体之间的结合模式。从分子建模研究中获得的信息可能有助于设计具有所需活性的新型 CDK2/细胞周期蛋白 A 抑制剂。
