Combined 3D-QSAR and Docking Modelling Study on Indolocarbazole Series Compounds as Tie-2 Inhibitors.
Tie-2, a kind of endothelial cell tyrosine kinase receptor, is required for embryonic blood vessel development and tumor angiogenesis. Several compounds that showed potent activity toward this attractive anticancer drug target in the assay have been reported. In order to investigate the structure-activity correlation of indolocarbazole series compounds and modify them to improve their selectivity and activity, 3D-QSAR models were built using CoMFA and CoMSIA methods and molecular docking was used to check the results. Based on the common sketch align, two good QSAR models with high predictabilities (CoMFA model: q(2) = 0.823, r(2) = 0.979; CoMSIA model: q(2) = 0.804, r(2) = 0.967) were obtained and the contour maps obtained from both models were applied to identify the influence on the biological activity. Molecular docking was then used to confirm the results. Combined with the molecular docking results, the detail binding mode between the ligands and Tie-2 was elucidated, which enabled us to interpret the structure-activity relationship. These satisf actory results not only offered help to comprehend the action mechanism of indolocarbazole series compounds, but also provide new information for the design of new potent inhibitors.
['Tian|Yuanxin|Y|', 'Xu|Jian|J|', 'Li|Zhonghuang|Z|', 'Zhu|Zhengguang|Z|', 'Zhang|Jiajie|J|', 'Wu|Shuguang|S|']
D002227:Carbazoles D006860:Hydrogen Bonding D057927:Hydrophobic and Hydrophilic Interactions D020128:Inhibitory Concentration 50 D008958:Models, Molecular D008968:Molecular Conformation D062105:Molecular Docking Simulation D056004:Molecular Dynamics Simulation D011485:Protein Binding D047428:Protein Kinase Inhibitors D021281:Quantitative Structure-Activity Relationship D042787:Receptor, TIE-2
docking CoMSIA 3D-QSAR, CoMFA Tie-2 kinase inhibitor