秋水仙碱位点抑制剂的结构特征研究

Study on the structural features of colchicine-site inhibitors

目的：寻找秋水仙碱结合位点抑制剂的结构特征。方法：将对接得到的8种不同结构抑制剂的结合构象进行叠合匹配,并结合已有的SAR结论来探讨。结果：整个结构由两个疏水基团A、B以及之间的桥链部分组成,但是在空间上A和B必须处于桥链的同侧。A基团的体积以及氢键受体基团的存在对活性有较大影响,B需为平面环且宜连接极性基团以增强结合,而桥链部分可以为1~4个长度的原子但以sp2杂化类型最佳。结论：研究得出的结构特征为设计新的秋水仙碱位点抑制剂提供了直观、简便的参考。

Objective：To determine the structural features of a set of diverse colchicines-site inhibitors. Methods：The features were revealed by matching the binding conformations generated from docking studies of eight inhibitors, and combined with the available SAR results. Results： The feature is represented as two hydrophobic groups （A and B） and a bridge linked between them, but A and B should be in the same side of the bridge, The volume size and the existence of hydrogen-bond acceptor of group A may have some influence on binding. Group B should be a hydrophobic planar ring, and polar functional group is advantageous, The bridge part could accept 1 -4 atoms, but the Sp2 hybrid is welcome. Conclusion：this result may provide useful insights for the design of novel Colchicine-site inhibitors.