Combined Molecular Docking,3D-QSAR,and Pharmacophore Model:Design of Novel Tubulin Polymerization Inhibitors by Binding to Colchicine-binding Site
Interfcrence wich dynamic equilibrium of microtubulc-tubulin has provcn to be a uscful tactics in the clinic.Based on investigation into the structure-activity relationship(SAR)studies of tuhulin polymcrization Inhibitors obtained from several worldwide groups.wc attempted to design 691 compounds covering several main heterocyclic scat-folds as no vel colchicinc site inhibitors(CSIs).Evaluated by a series of combination of commonly used computer methods such as molecular docking.3D-QSAR,and pharmacophorc modcl.wc can obtain the ultimatw 16 target compounds derived from five important basic scaffolds in the field of medicinal chemistry.Among these compounds,compound A-I32 with in silico modcrate activity was synthesized.and suhsequently validated ror preliminary inhibition of tubulin polymerization by immunofluorescence assay.In additional,the work of synthesis and validation of biological activity for other 15 various strueture compounds will be completed in our lab.This study not only developed a hierarchical strategy to screen novel tubulin inhibitors effectively,hut also widened the spectrum of chcmical structures of canonical CSls.
Microtubules Antitumor agents Colchicine-binding site 3D-QSAR Pharmacophore
Dong-Dong Li Ya-Juan Qin Xin Zhang Yong Yin Hai-Liang Zhu
College of Chemical Engineering,Nanjing Forestry University,Nanjing,210073,P.R.China State Key Laboratory of Pharmaccutical Biotechnology.School of Life Sciences,Nanjing University,Nanj
国内会议
大连
英文
84-118
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）