Synthesis,biological evaluation,and molecular docking studies of novel chalcone oxime derivatives as potential tubulin polymerization inhibitors
Microtubule-targeted drugs are at present indispensable for various types of cancer therapy worldwide.A series of chalcone oxime derivatives were designed,synthesized and evaluated as potential tubulin polymerization inhibitors and for the cytotoxicity against anthropic cancer cell lines.These derivatives were completely demonstrated to have commendable inhibitory activity against tubulin polymerization by competing with the colchicine-binding site on tubulin,which was associated with G2/M phase cell cycle arrest as well as promising antiproliferative activity.Among the novel compounds,compound 13 was demonstrated to have the most potent inhibitory activity(tubulin IC50 = 1.6 μM).Antiproliferative assay results displayed that compound 13 had potent antiproliferative activity against AS49,Hela and MCF-7 with Gl50 values of 2.1,3 5 and 3.6 μM,respectively,which were compared with the positive control colchicine and CA-4.Docking simulation showed that compound 13 could bind tightly to the colchicine domain of tubulin and act as a tubulin polymerization inhibitor.We also built a 3D-QSAR model to provide more information that could be applied to design new molecules with more potent tubulin inhibitory activity.
Yan-Ting Wang Ya-Juan Qin Ya-Liang Zhang Yu-Jing Li Bing Rao Yan-Qing Zhang Meng-Ru Yang Ai-Qin Jiang Jin-Liang Qi Hai-Liang Zhu
State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University,Nanj School of Medicine,Nanjing University,Nanjing 210093,P.R.China
国内会议
大连
英文
914-926
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）