CA4（Combretastatin A-4）是一种从南非风车子灌木中分离出来的活性化合物，它通过抑制微管蛋白聚合从而产生抗肿瘤活性。此项目基于点击化学策略，设计与合成一系列含氟CA4的三氮唑或四氮唑衍生物，并测试这些化合物的微管蛋白聚合抑制活性和细胞毒活性，运用计算机辅助药物设计方法，通过3D-QSAR、分子对接和分子动力学研究，探索它们与微管蛋白结合的作用机理，以及氟原子的引入对化合物活性的影响规律，以期发现拥有自主知识产权的高效低毒小分子靶向抗肿瘤新药。

CA4 (Combretastatin A-4), originally isolated from the South African willow tree Combretum caffrum, is an antitumor compound with potent inhibition of tubulin polymerization. 5 series of fluorinated CA4 derivatives with triazole or tetrazole skeleton will be designed and synthesized based on chick chemistry strategy, and their inhibitions effect on tubulin polymerization and the antitumor activities of all the derivatives will be assayed in vitro. The interaction mechanism of designed CA4 derivatives with tubulin will be studied with docking and molecular dynamic simulation. Their interaction mechanism with tubulin and the influence of the fluorine atoms on the activity of the compound will be explored through computer aided drug design methods, such as 3D-QSAR, molecular docking and molecular dynamics studies. We will discover novel small molecular targeting drugs with high efficiency and low toxicity, which possessing independent intellectual property rights.