combined 3d-qsar and docking modelling study on indolocarbazole series compounds as tie-2 inhibitors结合3 d-qsar和对接模型研究indolocarbazole系列化合物tie-2抑制剂.pdfVIP

Int. J. Mol. Sci. 2011, 12, 5080-5097; doi:10.3390/ijm OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Article Combined 3D-QSAR and Docking Modelling Study on Indolocarbazole Series Compounds as Tie-2 Inhibitors Yuanxin Tian, Jian Xu, Zhonghuang Li, Zhengguang Zhu, Jiajie Zhang * and Shuguang Wu School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; E-Mails: tyx523@163.com (Y.T.); woshixvjian@ 126.com (J.X.); lzhuang@ (Z.L.); zzg@ (Z.Z.); shuguang@ (S.W.) * Author to whom correspondence should be addressed; E-Mail: zhangjj@; Tel.:+86-20 Fax: +86-20 Received: 24 May 2011; in revised form: 1 August 2011 / Accepted: 2 August 2011 / Published: 10 August 2011 Abstract: 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: q2 = 0