N-芳基吲哚酮类衍生物的设计与合成及抗肿瘤活性研究

发布时间：2018-03-23 00:09

本文选题：吲哚　切入点：吲哚酮衍生物　出处：《天津科技大学》2014年硕士论文　论文类型：学位论文

【摘要】：在自然界中,吲哚杂环广泛的存在,在人们生活的各个领域都扮演着重要的角色。吲哚酮是吲哚衍生物中十分重要的一类化合物,具有广泛的生物活性。靛红及其衍生物具有很好的抗肿瘤活性、抗细菌活性、抗真菌活性、抗病毒活性和抗HIV病毒活性等,其对中枢神经系统的作用也被广泛的研究。虽然吲哚酮类化合物的1-位,3-位和苯环上的衍生物已有较多报道,但对吲哚酮1-位,3-位和5-位多位点修饰的报道较少,因此,本论文对N-芳基吲哚酮衍生物的1-位,3-位和5-位进行了设计和合成及生物活性的研究。本课题以靛红(吲哚酮)或对溴苯胺为原料,共进行了六步反应,首先靛红的1-位N上连接芳环基团,然后通过黄鸣龙还原反应还原靛红3-位羰基,接下来通过Suzuki偶联反应或heck反应对5位进行修饰。本论文共合成了78个化合物,其中52个未见报道,经1H NMR,1C NMR确证其结构。采用MTT法对58个目标化合物和重要中间体进行了抑制肿瘤细胞生长活性测试,活性测试选用了三种癌细胞：人肝癌细胞HepG2,人白血病细胞K562,人结肠癌细胞HT-29。MTT测试结果表明：3-位引入苄基后的活性要高于其前体,5-位上为H的化合物在变为Br后活性明显提升,1-位引入芳基后的活性能够维持或稍有提高。其中化合物5-溴-3-(4-三氟甲基亚苄基)-1-(4-甲氧基苯基)二氢吲哚-2-酮对K562、 HT-29、HepG2的IC50值分别达到2.21μM、9.95μM和69.341μM。
[Abstract]:In nature, indole heterocycles exist widely and play an important role in all fields of human life. Indole is a very important class of compounds in indole derivatives. Indirubin and its derivatives have good antitumor, antibacterial, antifungal, antiviral, antiviral and antiviral activities, etc. The effects of indole on the central nervous system have also been extensively studied. Although there have been many reports on the 1- and 3-site of indole compounds and the derivatives on benzene ring, there are few reports on the modification of indole 3-site and 5-site multisite modification of indole. In this paper, the design and synthesis of 1-site 3-site and 5-site of N-aryl indoleone derivatives were studied. In this paper, we used indole (indole) or p-bromoaniline as raw materials, and carried out a six-step reaction. First, the aromatic ring group was connected to the 1-position N of indirubin, then the 3-position carbonyl of indirubin was reduced by Huang Minglong, and then modified by Suzuki coupling reaction or heck reaction. In this paper, 78 compounds were synthesized. 52 of them were confirmed by 1H NMRN 1C NMR. The inhibitory activity of 58 target compounds and important intermediates on tumor cell growth was tested by MTT method. Three kinds of cancer cells were selected for activity test: human hepatoma cell line HepG2, human leukemia cell line K562. the results of HT-29.MTT test of human colon cancer cell line showed that the activity of the benzyl group introduced into the cell line was higher than that of the compound with H at the 5- site of the cancer cell. The activity of 5-bromo-3-pyrrolidene 4-trifluoromethylbenzylidene) dihydroindole-2-one for K562and HT-29Hep G2 was 2.21 渭 M9.95 渭 M and 69.341 渭 M, respectively.
【学位授予单位】：天津科技大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914;R96

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