含吡咯环的缩氨基硫脲衍生物及其配合物的合成、表征和生物活性研究

发布时间：2018-02-26 09:01

本文关键词： 缩氨基硫脲吡咯晶体抗肿瘤药物　出处：《河南理工大学》2015年硕士论文　论文类型：学位论文

【摘要】：缩氨基硫脲类化合物因其具有的广泛而突出的抗菌、抗肿瘤、抗疟疾及抗病毒等生物活性引起了广大科学工作者的极大关注。因此,缩氨基硫脲类化合物在医药和农药开发和研究等领域扮演着越来越重要的角色。本论文对有关缩氨基硫脲配体化合物及其相关金属配合物的合成及生物活性研究方面的工作进行了探索,并对今后该类化合物的继续研究进行了展望。本文中选择将具有不同N4-位取代基的氨基硫脲(硫代氨基脲、4-甲基-3-氨基硫脲、4-乙基-3-氨基硫脲、4-异丙基-3-氨基硫脲、4-苯基-3-氨基硫脲)与含氮杂环吡咯醛(2,4-二甲基-5-醛基-吡咯-3-甲酸乙酯、2-乙氧羰基-3,4-二甲基-5-甲酰基吡咯和5-甲酰基-1H-吡咯-2-甲酸乙酯)进行缩合反应得到的15个吡咯衍生物作为配体。采用元素分析、核磁、红外等手段对它们进行了结构表征,同时还得到其中5个缩氨基硫脲配体的单晶并确定它们的晶体结构。利用这些配体合成了它们相应的Cu(II)、Ni(II)金属配合物,同时也通过单晶衍射确定了部分配合物的晶体结构。此外,本文还采用MTT法测试了部分配体配合物对人腺癌细胞株PC-9、人食管癌细胞株Eca109、人胃癌细胞株SGC7901、人肺癌细胞株A549、人胃癌细胞株BGC823、结直肠癌细胞LOVE或人胰腺癌细胞8898的半数抑制浓度(IC50值)。抗肿瘤测试结果表明,就各种试验的人体肿瘤细胞而言,合成所得的一系列化合物都表现出优秀的抑制作用,尤其是配合物的IC50值基本保持在40μM以下。由此可见,吡咯缩氨基硫脲类化合物可以作为一种潜在的抗肿瘤药物而被广泛地研究和应用于实践。总之,通过化学的方法修饰缩氨基硫脲分子的骨架结构可得到一系列新的缩氨基硫脲化合物。再利用该类化合物与过渡金属离子配位形成金属有机配合物后生物活性明显增强的特性,可能开发研制出高效、低毒、低残留的新型药物和农药。
[Abstract]:Thiosemicarbazide compounds have attracted great attention of scientists because of their extensive and prominent antibacterial, anti-tumor, anti-malaria and anti-virus biological activities. Thiosemicarbazide compounds play an increasingly important role in the field of medicine and pesticide development and research. Synthesis and bioactivity of thiosemicarbazone ligand compounds and their related metal complexes. The work in this area has been explored, In this paper, the thiosemicarbazone with different N _ 4-position substituents is selected. The thiosemicarbazone 4-ethyl-3-aminothiosemicarbazone 4-isopropyl -3-aminothiocarbazone is selected in this paper, where the thiosemicarbazone is 4-methyl-3-aminothiosemicarbazone (thiosemicarbazone). The condensation reaction of 4-phenyl-3-thiosemicarbazone with nitrogen-containing heterocyclic pyrrolidene 2-dimethyl-5aldehyde-pyrrole-3-formate ethyl ester, 2-ethoxycarbonyl -3-dimethyl-5-formyl pyrrole and 5-formyl -1H-pyrrole-2-formate was obtained. 15 pyrrole derivatives were used as ligands for elemental analysis, Their structures were characterized by NMR and IR, and the crystal structures of five thiosemicarbazide ligands were obtained and their crystal structures were determined. Their corresponding metal complexes were synthesized by using these ligands. At the same time, the crystal structure of some complexes was determined by single crystal diffraction. MTT assay was used to detect the effects of partial ligand complexes on human adenocarcinoma cell line PC-9, human esophageal carcinoma cell line Eca109, human gastric cancer cell line SGC7901, human lung cancer cell line A549, human gastric cancer cell line BGC823, colorectal cancer cell line LOVE or human pancreatic cancer cell line 8898. The IC50 value of 50% inhibition concentration and the results of antitumor test showed that, For human tumor cells in various experiments, the synthesized series of compounds exhibit excellent inhibitory effects, especially the IC50 value of the complexes remains below 40 渭 M. Pyrrolidine thiosemicarbazone compounds can be widely studied and applied as a potential antitumor drug. A series of new thiosemicarbazone compounds can be obtained by modifying the skeleton structure of thiosemicarbazone by chemical method. It is possible to develop new drugs and pesticides with high efficiency, low toxicity and low residue.
【学位授予单位】：河南理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：O641.4

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