一珠二化合物组合化学法合成喹唑啉酮类化学库及其抗肺癌活性的初步筛选  

Design,synthesis and screening of one-bead two-compound quinazolinone library for anti-cancer activity against lung cancer

作　　者：王琼 郑锦鸿 王锦芝 刘瑞武 WANG Qiong;ZHENG Jinhong;WANG Jinzhi;LIU Ruiwu(Department of Chemistry,Shantou University Medical College,Shantou 515041,China;Department of Biochemistry and Molecular Medicine,University of California,Davis 95817,U.S.A)

机构地区：[1]汕头大学医学院化学教研室,广东汕头515041 [2]加州大学戴维斯分校生物化学和分子医药系,加利福尼亚戴维斯95817

出　　处：《汕头大学医学院学报》2021年第1期1-6,共6页Journal of Shantou University Medical College

基　　金：广东省医学科研基金(A2017322)。

摘　　要：目的:探讨一珠二化合物组合化学库结合高通量筛选的方法,为了获得小分子多靶点新型2-喹唑啉酮先导化合物以阻断肺癌的发生及发展进程。方法:以四功能分子骨架N-Alloc-3-氨基-3-(2-氟-5-硝基苯)丙酸为模板,合成具有分子多样性的喹唑啉酮化学库;以免疫细胞化学法对肺癌细胞株H1975进行高通量筛选。结果:合成了容量为800个小分子化合物的喹唑啉酮化合库,经高通量筛选得到阳性化合物CA10。结论:CA10表现较好的抑制肺癌细胞活性,可作为先导化合进行进一步优化结构。Objective:To investigate the method of one-bead two-compound combinatorial chemical library combined with high-throughput screening,in order to obtain a small molecule multi-target novel 2-quinazolinone lead compound to block the occurrence and development of lung cancer.Methods:N-Alloc-3-amino-3-(2-fluoro-5-nitrophenyl)propionic acid was used as tetrafunctional scaffold to generate diversity for quinazolinone library,the anti-cancer activity was detected with immunocytochemistry assay on H1975 cells.Results:The onebead two-compound library permutation was 800 small molecule compounds.One positive bead with compounds CA10 was identified by high-throughput screening.Conclusion:CA10 inhibited viability of lung cancer and would be most promising to modify as lead compound.

关 键 词：喹唑啉酮 组合化学 肺癌 

分 类 号：R914.4[医药卫生—药物化学]