含嘌呤取代的查尔酮类衍生物的设计合成与生物活性研究

发布时间：2018-11-22 17:51

【摘要】：本论文在查尔酮化合物中引入具有广泛生物活性的嘌呤环,设计合成一系列含嘌呤取代的查尔酮类衍生物3a-3z,并以黄瓜花叶病毒与烟草花叶病毒为研究对象,采用半叶枯斑法对目标化合物进行活体内抗植物病毒活性测试;并对目标化合物与TMV CP之间的相互作用进行了初步探究。本论文的工作总结概括如下:1.以天然产物查尔酮为先导化合物,通过活性结构拼接原理,将同样具有广泛生物活性的嘌呤环引入查尔酮结构中,设计合成了26个新型含嘌呤取代的查尔酮衍生物3a-3z。所有的化合物均通过了1H NMR、13C NMR、HRMS和元素等结构表征。2.以宁南霉素和病毒唑(利巴韦林)作为对照药剂,采用半叶枯斑法,测试目标化合物对黄瓜花叶病毒(CMV)和烟草花叶病毒(TMV)的抑制活性。结果表明:在浓度为500μg/mL时,大部分化合物对CMV表现出较好的治疗活性,因此进一步测试了目标化合物抗CMV治疗活性的EC50值,其中化合物3o(EC50=301.1μg/mL)、3s(EC50=315.7μg/mL)、3w(EC50=282.3μg/mL)和3x(EC50=230.5μg/m L)对CMV的治疗活性优于宁南霉素(EC50=343.8μg/mL)。在抗TMV活性方面,化合物3o和3p的表现出较好的钝化活性,分别为89.1%和88.2%,与宁南霉素相当(89.5%)。3.采用荧光光谱检测法,进一步探究部分目标化合物与TMV CP之间的相互作用,结果表明高活性化合物3o与TMV CP之间具有较强的亲和力。
[Abstract]:In this paper, a series of chirone derivatives 3a-3zcontaining purine substituents were designed and synthesized by introducing a wide range of purine rings into chalcone compounds. Cucumber mosaic virus and tobacco mosaic virus were studied. The in vivo anti-virus activity of the target compound was tested by half-leaf spot method. The interaction between the target compound and TMV CP was studied. The work of this paper is summarized as follows: 1. With the natural product chalcone as the lead compound, 26 new derivatives 3a-3zwith purine substituent were designed and synthesized by introducing the purine ring, which also has extensive biological activity, into the structure of chalcone by the principle of active structure splicing. All the compounds were characterized by 1H NMR,13C NMR,HRMS and elemental structure. The inhibitory activities of the target compounds against cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV) were tested by semi-leaf blight spot method with Ningnanmycin and ribavirin (ribavirin) as control agents. The results showed that at the concentration of 500 渭 g/mL, most of the compounds showed better therapeutic activity to CMV, so the EC50 value of the target compound's anti-CMV therapeutic activity was further tested, in which compound 3o (EC50=301.1 渭 g/mL), 3s (EC50=315.7 渭 g/mL), 3w (EC50=282.3 渭 g/mL) and 3x (EC50=230.5 渭 g / mL) were superior to EC50=343.8 渭 g/mL in the treatment of CMV. The anti- TMV activity of compounds 3o and 3p were 89.1% and 88.2% respectively, which were equivalent to those of Ningnanmycin (89.5%). The interaction between some target compounds and TMV CP was further investigated by fluorescence spectrometry. The results showed that the highly active compound 3o had strong affinity with TMV CP.
【学位授予单位】：贵州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.3;TQ450.1

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