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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 a new HIV-1 integrase inhibitor. METHODS: Using de novo drug design methodology, 3220 compounds were generated starting from the active site of the styrylquinoline inhibitors and integrase. At the same time, the binding energy and binding mode of these compounds to integrase were simulated by molecular docking. Results: These compounds were designed to bind to the active region of HIV-1 integrase and contain four new structures not found in known styryl quinoline inhibitors: vinylnaphthalene, styrylbenz Anthracene, styrylbenzoquinolines and heterocycles. CONCLUSION: This study is of guiding significance for further structural modification of styryl quinoline inhibitors and development of a new HIV-1 integrase inhibitor.