Molecular docking and 3D-QSAR studies on checkpoint kinase 1 inhibitors

作者：Hu, Shiyuan; Yu, Haijing; Zhao, Lingzhou; Liang, Aihua; Liu, Yongjuan; Zhang, Huabei^*

来源：Medicinal Chemistry Research, 2013, 22(10): 4992-5013.

DOI：10.1007/s00044-013-0471-1

• Checkpoint kinase 1
• CoMFA
• CoMSIA
• Molecular docking
• 3D-QSAR

Checkpoint kinase 1(Chk1) is a promising target for cancer treatment. Here three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on 174 1,4-dihydroindeno[1,2-c]pyrazole inhibitors of Chk1 using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Two satisfactory ligand-based QSAR models were built (CoMFA model: q (2) = 0.541, r (2) = 0.880, CoMSIA model: q (2) = 0.590, r (2) = 0.902). The docking-based studies presented a detailed understanding of interaction between the inhibitors and Chk1. The obtained QSAR models are highly predictable (CoMFA model: q (2) = 0.567, r (2) = 0.891, CoMSIA model: q (2) = 0.596, r (2) = 0.917). The models were further validated by an external testing set obtaining values 0.896 and 0.923 for CoMFA and CoMSIA, respectively. So our models might be helpful for further modification of 1,4-dihydroindeno[1,2-c]pyrazole derivatives.

• 出版日期2013-10
• 单位北京师范大学