3D-QSAR and Docking Studies on 2-acyliminobenzimidazoles Derivatives as Potent ALK Inhibitors

Title:3D-QSAR and Docking Studies on 2-acyliminobenzimidazoles Derivatives as Potent ALK Inhibitors

Volume: 12 Issue: 3

Author(s): Qianqian Lva, Zhi Wang, Zhonghua Wanga*, Fanhong Wu*Liping Cheng

Affiliation:

• School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai,China

• School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai,China

Keywords: 3D-QSAR, ALK inhibitor, CoMFA, CoMSIA, docking.

Abstract: The overexpression of anaplastic lymphoma kinase (ALK) had been found in many types of cancers, especially the non-small-cell lung cancers (NSCLCs). So the discovery of novel ALK inhibitor had attracted a great deal of interest in anticancer drugs research area. Presently, a combined study of 3D-quantitative structure-activity relationship (3DQSAR) and molecular docking was undertaken to explore the structural insights of 36 2-acyliminobenzimidazoles compounds influencing the ALK inhibitory activities. Both the ligand-based resultant comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models exhibited good predictability (CoMFA with R², 0.995; q², 0.534; CoMSIA with R², 0.993; q², 0.519;). 3D contour maps and docking results suggested different groups on the core parts of the componds could enhance the biological activities. Finally, 10 derivatives as potential candidates of ALK inhibitors with excellent predicted activities were designed.

Cite this article as:

Lva Qianqian, Wang Zhi, Wanga Zhonghua*, Wu Fanhong*, Cheng Liping, 3D-QSAR and Docking Studies on 2-acyliminobenzimidazoles Derivatives as Potent ALK Inhibitors, Letters in Drug Design & Discovery 2015; 12 (3) . https://dx.doi.org/10.2174/1570180811666141010001624