螺吡喃环小分子化合物的构建及其性能研究

发布时间：2018-05-12 14:41

本文选题：螺吡喃 + Cu~(2+)　；参考：《遵义医学院》2017年硕士论文

【摘要】：目的:构建新的含螺吡喃环小分子化合物并探寻其分子识别性能和抗肿瘤活性。方法:以吲哚啉为原料,将其分别与2,6-二甲酰基-4-甲基苯酚、2,6-二甲酰基-4-叔丁基苯酚缩合反应得到含螺吡喃环的中间体L1和L2;再将螺吡喃中间体L1与氮芥衍生物(N,N-二氯乙基-对苯二胺)缩合反应得含氮芥的螺吡喃环小分子化合物L3;对比化合物以费舍尔氏醛与氮芥衍生物(N,N-二氯乙基-对苯二胺)缩合得到含氮芥的小分子化合物L4。利用1H NMR,13C NMR,FT-IR,质谱等分析技术进行其结构的表征。并应用荧光分光光度计和紫外-可见分光光度计考察了L1和L2的识别性能;采用MTT法考察了L3和L4对肿瘤细胞的抗肿瘤活性。结果:成功合成并表征了L1,L2,L3和L4。经研究发现:中间体L1和L2在无水乙醇与Tris-HCl(1/1,v/v,pH=7.40)的混合溶剂中能特异选择性识别Cu~(2+)和水合肼,且可实现对Cu~(2+)的裸眼比率识别。制成负载有L1和L2的试纸条能实现裸眼识别检测水样中μmol/L级的Cu~(2+),制备负载有L1和L2的TLC板及试纸片能实现在365 nm紫外灯下对液体和气体水合肼的裸眼识别。L1和L2可应用于水样和药物中Cu~(2+)或水合肼测定的回收率分别在83.5%~111.0%、72.6%~111.0%之间,相对标准偏差(RSD%)分别小于4.0%和3.0%。L2可应用于活细胞中水合肼的成像;抗肿瘤化合物L3和L4对A549和HepG2两种细胞都具有一定的细胞毒性,且L3对A549的细胞毒性优于顺铂,其抑制率IC50是顺铂的3.5倍。结论:L1和L2可作为高选择性识别Cu~(2+)和水合肼的化学传感器;L3可作为抗A549肿瘤细胞的潜在先导化合物。含螺吡喃结构的小分子在多功能识别性能以及作为抗肿瘤先导化合物研究中具有其潜在的应用前景。
[Abstract]:Aim: to construct a new small molecular compound containing spiropyran ring and to explore its molecular recognition and anti-tumor activity. Methods: indoline was used as raw material. The intermediate L1 and L _ 2 containing spiropyran ring were obtained by condensation reaction of 2-butadiyl -4-methylphenol and 2-diformyl-6-diformyl-4-tert Ding Ji phenol, respectively, and then the intermediate L1 and nitrogen mustard derivative (N-N-dichloroethyl-p-phenylenediamine) were synthesized. The spiropyran ring small molecular compound L3 containing nitrogen mustard was synthesized by condensation reaction, and the small molecule compound L4 containing nitrogen mustard was synthesized by condensation of Fischer aldehyde with nitrogen mustard derivative N (N-dichloroethyl-p-phenylenediamine). Its structure was characterized by 1H-NMR-13C NMR-FT-IRand mass spectrometry. The recognition properties of L1 and L2 were investigated by fluorescence spectrophotometer and UV-Vis spectrophotometer, and the antitumor activity of L3 and L4 on tumor cells was investigated by MTT method. Results: L1, L2, L3 and L4 were successfully synthesized and characterized. It has been found that the intermediates L1 and L2 can specifically identify Cu~(2 and hydrazine hydrate in the mixture of anhydrous ethanol and Tris-HCln (1 / 1 / 1 / v / v pH = 7.40), and can realize the naked eye ratio recognition of Cu~(2). The test strips loaded with L1 and L2 can be used to detect the 渭 mol/L grade Cu~(2 in water samples. The TLC plates loaded with L1 and L2 and the test sheets can recognize liquid and gas hydrazine hydrate by naked eyes under 365nm UV lamp. The recoveries of L2 for the determination of Cu~(2 in water samples and drugs) or hydrazine hydrate were 83.5% and 111.0%, respectively. The relative standard deviation (RSD) is less than 4.0% and 3.0%.L2 can be used in the imaging of hydrazine hydrate in living cells, the antitumor compounds L3 and L4 are cytotoxic to both A549 and HepG2 cells, and the cytotoxicity of L3 to A549 is better than that of cisplatin. The inhibition rate of IC50 was 3.5 times higher than that of cisplatin. Conclusion 1: L1 and L2 can be used as chemical sensors for highly selective recognition of Cu~(2) and hydrazine hydrate as potential lead compounds for anti-A549 tumor cells. Small molecules with spiropyran structure have potential applications in the study of multifunctional recognition and antitumor precursor compounds.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R914;R96

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