计算机辅助CDK6抑制剂先导化合物初步设计及化合物活性的测定

【关键词】  计算机辅助药物设计

    Computerassisted primary design of lead compounds of CDK6 inhibitors and determination of their bioactivity

　　【Abstract】 AIM: To primarily design the lead compounds of CDK16 inhibitors based on CDK6 structure and to test their bioactivity. METHODS: Using LigBuilderv1.2 ［a kind of computerassisted drug design (CADD) program］, we tried to design new lead compunds of CDK6 inhibitors by method of de novo design and according to Lipinski rule, and test their IC50 by MTT assay. RESULTS: We got the structures of 50 new chemical compounds as the lead compounds for further drug filtering, and 3 of 8 compunds we synthesized successfully had a bioactivity between 220 and 310 μmol/L. CONCLUSION: The new compunds have some inhibitory activity and the efficiency of finding lead compounds can be improved with the help of CADD.

　　【Keywords】 CADD; CDK6 inhibitor; IC50

　　【摘要】 目的： 初步设计CDK6抑制剂先导化合物，并测定化合物活性. 方法：利用计算机辅助药物设计（CADD）程序LigBuilderv1.2，依据Lipinski法则，采用从头设计、片断生长的方法，在Linux操作系统下，设计全新CDK6抑制剂化合物；MTT法测定化合物IC50. 结果：得到50种化合物结构并成功合成8种，经测定其中3种有活性（IC50在220~310 μmol/L间）. 结论：新型CDK6抑制剂化合物具有一定抑制活性，CADD可以大大提高先导化合物发现的效率，加快新药研究的步代.

　　【关键词】 计算机辅助药物设计; CDK6抑制剂; IC50