摘要
目的:合理设计新的HIV-1整合酶抑制剂。方法:采用从头药物设计方法,从苯乙烯基喹啉抑制剂与整合酶的活性位点出发,产生3220个化合物。同时,通过分子对接方法模拟分析这些化合物与整合酶的结合能和结合模式。结果:设计产生的这些化合物能结合于HIV-1整合酶的活性区域中,包含4类在已知苯乙烯基喹啉类抑制剂中没有的新结构:乙烯基萘类、苯乙烯基苯并氮蒽类、苯乙烯基苯并喹啉类和杂环类。结论:本研究对进一步进行苯乙烯基喹啉类抑制剂的结构改造以及研制新的HIV-1整合酶抑制剂具有一定的指导意义。
Objective： To rationally design new inhibitors of HIV-1 integrase. Methods： 3 220 compounds were designed from the binding mode of styrylquinoline derivatives in integrase active site using a de novo drug design method, and evaluated by docking simulation. Results： These compounds could be bound to the active cavity of HIV-1 integrase. Four different series of compounds possessed structural features not seen in known styrylquinoline inhibitors,including vinylnaphthalene, styrylbenzoacridine, styrylbenzoquinoxaline and heterocyclic compounds. Conclusion： This work provides us with helpful hints for further optimization of styrylquinoline integrase inhibitors and design of novel anti-HIV integrase inhibitors.
出处
《军事医学科学院院刊》
CSCD
北大核心
2005年第4期355-358,共4页
Bulletin of the Academy of Military Medical Sciences
基金
北京市自然科学基金项目(5032002
5042003)
北京市教委重点基金资助项目(KZ200410005002)
