嘧啶并喹啉类化合物的设计 合成及初步生物活性分析-design, synthesis and preliminary biological activity analysis of pyrimidino quinoline compounds.docx

中南民族大学硕士学位论文 嘧啶并喹啉类化合物的设计、合成及初步生物活性研究 I II 摘 要 嘧啶并喹啉类杂环化合物由于具有杀菌、抗炎止痛、抗病毒、抗疟疾及抗癌 等多种生物活性，受到有机化学家和医药学家的广泛关注。本研究主要运用条件 温和的 aza-Wittig 反应来设计、合成嘧啶并喹啉类杂环化合物，并探索了此类化合 物的成环条件、波谱性质以及生物活性，发现部分化合物具有一定的抗癌细胞活 性和杀菌活性。 具体研究内容如下： 1、 总结了近年来嘧啶并喹啉类杂环化合物的合成研究进展。 2、 应用 aza-Wittig 反应方法合成了 39 个新的未见文献报道的嘧啶并[5,4-c]喹 啉-4-(3H)-酮衍生物，其结构经 IR、1H NMR、13C NMR、MS 表征，部分化合物结 构经 2D-NMR 的归属确认。 3、 部分目标化合物进行初步的生物活性筛选，包括体外抗肿瘤细胞活性测试 和体外抗菌活性测试。 结果表明：目标化合物 10b [MGC-803 IC50(μM) = 14.7]、6a [MGC-803 IC50(μM) = 15.8]、6j [MGC-803 IC50(μM) = 15.3]和 6m [KB IC50(μM) = 4.9，CNE2 IC50(μM) = 13.8，MGC-803 IC50(μM) = 4.8，GLC-82 IC50(μM) = 7.88，MDA-MB-453 IC50(μM) = 18.2，MCF-7 IC50(μM) = 10.1]对某些细胞表现出较好肿瘤细胞抑制作用，这 4 个 化合物可作为先导化合物，进一步进行结构修饰和改造，以期获得抗肿瘤活性更 好和选择性更高的化合物；化合物 6g 表现出较好的抑制枯草芽孢杆菌的抑菌效果， 可作为先导化合物进一步进行结构修饰和改造，以期获得较理想的具有抗菌活性 的化合物。 4、 初步探索了目标化合物与 PTK 的对接，结果显示，化合物 6m 与 PTK 连 接良好。 关键词：嘧啶并[5,4-c]喹啉-4-(3H)-酮衍生物，aza-Wittig 反应，杀菌活性，抗肿瘤 活性  Abstract Pyrimidoquinoline derivatives have been appealed to organic, medicinal and materials scientists due to their extremely various biological activities show many biological activities, such as anti-microbial, anti-inflammatory , analgesic, antiviral, antimalarial and antitumor. In this paper, a series of novel unreported pyrimido[5,4-c]quinoline derivatives have been designed and synthesized via aza-Wittig reaction with mild condition. Furthermore, their cyclization conditions, spectral properties and biological activities have been explored. The dissertation could be summarized as follows: The research progress of pyrimidoquinoline derivatives were summarized. 39 new compounds were design and synthesized and the structure elucidation was accomplished by using IR, 1H NMR, 13C NMR, MS, and parts of them were further confirmed by 2D-NMR. 19 compounds were tested in vitro antimicrobial activities and 24 compound compounds were tested in vitro antitumor activities. Among them compound 10b, 6a, 6j and 6m showed good in vitro antitumor activities: 10b [MGC-803 IC50(μM) = 14.7], 6a [MGC-803