含吡啶的戊二烯酮肟醚类衍生物的合成及其生物活性研究
发布时间：2018-11-09 08:18
【摘要】：1,4-戊二烯-3-酮类化合物,作为一种重要的姜黄素衍生物,具有抑菌、抗肿瘤、抗氧化、抗炎、杀虫、抗病毒和杀虫等广泛的生物活性,已成为药剂创制工作中的热点之一。近年来的研究发现此类化合物表现有明显的抗植物病毒活性。同时,肟醚类化合物也具有高效、广谱和作用方式较为独特的特点,在农药的创制过程中起到了重要的作用。鉴于此,我们将1,4-戊二烯-3-酮结构中的羰基改变为肟醚结构,设计合成了系列分子中分别含有吡啶、喹唑啉-4(3H)-酮和香豆素结构的1,4-戊二烯-3-酮肟醚类化合物,所得化合物均通过了IR、1H NMR、13C NMR和HRMS或ESI-MS验证。本论文主要研究工作概括如下:1.设计合成了18个分子中含吡啶的1,4-戊二烯-3-酮肟醚类化合物,并采用半叶枯斑法,以病毒唑为对照药剂,测试了该系列化合物在质量浓度为500μg/mL下对TMV的抑制活性。生物活性测试结果表明该系列化合物对TMV具有良好的抑制活性。在治疗活性方面,化合物A1、A2、A3、A7、A8、A10、A15和A16对TMV的抑制活性分别为45.4、40.3、49.4、43.1、39.8、45.1、54.6和47.6%,优于病毒唑(36.2%);在保护活性方面,化合物A1、A5、A12、A15和A16对TMV的抑制活性分别为58.5、54.4、59.9、70.2和60.3%,优于病毒唑(53.4%);在钝化活性方面,化合物A15和A16对TMV的抑制活性分别为86.8和78.1%,优于病毒唑(77.3%)。进一步的研究表明:化合物A3、A10、A15和A16对TMV治疗活性的EC50值分别为274.8、299.2、251.8和287.7μg/mL,优于病毒唑(379.8μg/mL)。2.设计合成了17个分子中含喹唑啉-4(3H)-酮的1,4-戊二烯-3-酮肟醚类化合物,并采用半叶枯斑法,以宁南霉素为对照药剂,测试了该系列化合物在质量浓度为500μg/mL下对TMV的抑制活性。生物活性测试结果表明该系列化合物对TMV具有良好的抑制活性。在治疗活性方面,化合物B3、B4、B5、B10、B11和B16对TMV的抑制活性分别为55.9、53.4、54.6、55.4、59.1和53.5%,优于宁南霉素(51.8%);在保护活性方面,化合物B3、B10和B11对TMV的抑制活性分别为69.8、67.7和72.0%,优于宁南霉素(65.7%)。进一步的研究表明:化合物B3、B10和B11对TMV治疗活性的EC50值分别为138.5、132.9和125.6μg/mL,优于宁南霉素(207.2μg/mL)。3.设计合成了5个分子中含香豆素的1,4-戊二烯-3-酮肟醚类化合物,并采用半叶枯斑法,以病毒唑为对照药剂,测试了该系列化合物在质量浓度为500μg/mL下对TMV的抑制活性。生物活性测试结果表明该系列化合物对TMV具有中等程度的抑制活性。其中,在治疗活性方面,化合物C3、C4和C5对TMV的抑制活性分别为38.9、38.8和42.5%,优于病毒唑(36.2%)。4.采用浊度法,以商品化药剂叶枯唑为对照药剂,测试了部分化合物在质量浓度为100和50μg/m L下对水稻白叶枯病菌和烟草青枯病菌的体外抑制活性。初筛结果表明,该系列在药剂浓度为100和50μg/mL下对以上两种细菌的抑制活性相对较低。
[Abstract]:As a kind of important curcumin derivative, 1C _ 4-pentadiene-3-one has a wide range of biological activities, such as bacteriostatic, anti-tumor, anti-oxidation, anti-inflammatory, insecticidal, antiviral and insecticidal. Has become one of the hot spots in the pharmaceutical production work. In recent years, it has been found that these compounds exhibit obvious anti-plant virus activity. At the same time, oxime ether compounds also have the characteristics of high efficiency, wide spectrum and unique mode of action, and play an important role in the process of pesticide production. In view of this, we changed the carbonyl group of 1-pentadiene-3-one structure into oxime ether structure, and designed and synthesized a series of molecules containing pyridine respectively. The structures of quinazoline-4 (3H) -ketone and coumarin were confirmed by IR,1H NMR,13C NMR, HRMS or ESI-MS. The main research work of this thesis is summarized as follows: 1. Eighteen compounds containing pyridine were designed and synthesized. The inhibitory activity of these compounds against TMV at a concentration of 500 渭 g/mL was tested by semi-withered spot method and virazole as control. The results of bioactivity test showed that this series of compounds had good inhibitory activity to TMV. In terms of therapeutic activity, the inhibitory activities of compound A1A1A2A2OA3A7A7, A10A10, A15 and A16 on TMV were 45.4%, 40.3%, 49.4% and 49.8%, respectively, which were superior to virazole (36.2%). In terms of protective activity, the inhibitory activities of compounds A _ (1) A _ (5) A _ (12) A _ (15) and A _ (16) on TMV were 58.5% (54.4N) 70.2 and 60.3%, respectively, which were superior to ribavirin (53.4%). In terms of passivation activity, the inhibitory activities of compounds A15 and A16 on TMV were 86.8 and 78.1, respectively, which were superior to virazole (77.3%). Further studies showed that the EC50 values of A3A10A15 and A16 for TMV were 274.8299.2251.8 and 287.7 渭 g / mL, respectively, which were better than that of ribavirin (379.8 渭 g/mL). In this paper, 17 compounds containing quinazoline-4 (3H) -ketone were designed and synthesized. The inhibitory activity of the compounds to TMV at a concentration of 500 渭 g/mL was tested. The results of bioactivity test showed that this series of compounds had good inhibitory activity to TMV. In terms of therapeutic activity, the inhibitory activities of compounds B3OB4OB5OB10B11 and B16 on TMV were 55.9% and 54.6%, respectively, which were better than those of Ningnanmycin (51.8%). In terms of protective activity, the inhibitory activities of compounds B _ (3) B _ (10) and B _ (11) on TMV were 69.8% and 72.0%, respectively, which were superior to those of Ningnanmycin (65.7%). Further studies showed that the EC50 values of compound B _ 3N _ (10) and B _ (11) for TMV were 138.5132.9 and 125.6 渭 g / mL, respectively, which were superior to those of Ningnanmycin (207.2 渭 g/mL). Five monopentadiene-3-ketoxime ethers containing coumarin were designed and synthesized. The inhibitory activity of these compounds against TMV at a concentration of 500 渭 g/mL was tested by half-leaf spot method and virazole as control. The results of bioactivity test showed that this series of compounds had moderate inhibitory activity to TMV. The inhibitory activities of C _ 3C _ 4 and C _ 5 on TMV were 38.9% and 42.5 respectively, which were better than that of ribavirin (36.2%). The inhibitory activities of some compounds against bacterial blight of rice and tobacco bacterial wilt were tested by turbidimetric method and commercial fungicide, leaf kudazole, at mass concentration of 100 渭 g / mL and 50 渭 g / mL, respectively. The results showed that the inhibitory activity of this series against the above two bacteria was relatively low at the concentration of 100 渭 g/mL and 50 渭 g/mL.
【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】：O626;TQ450.1
[Abstract]:As a kind of important curcumin derivative, 1C _ 4-pentadiene-3-one has a wide range of biological activities, such as bacteriostatic, anti-tumor, anti-oxidation, anti-inflammatory, insecticidal, antiviral and insecticidal. Has become one of the hot spots in the pharmaceutical production work. In recent years, it has been found that these compounds exhibit obvious anti-plant virus activity. At the same time, oxime ether compounds also have the characteristics of high efficiency, wide spectrum and unique mode of action, and play an important role in the process of pesticide production. In view of this, we changed the carbonyl group of 1-pentadiene-3-one structure into oxime ether structure, and designed and synthesized a series of molecules containing pyridine respectively. The structures of quinazoline-4 (3H) -ketone and coumarin were confirmed by IR,1H NMR,13C NMR, HRMS or ESI-MS. The main research work of this thesis is summarized as follows: 1. Eighteen compounds containing pyridine were designed and synthesized. The inhibitory activity of these compounds against TMV at a concentration of 500 渭 g/mL was tested by semi-withered spot method and virazole as control. The results of bioactivity test showed that this series of compounds had good inhibitory activity to TMV. In terms of therapeutic activity, the inhibitory activities of compound A1A1A2A2OA3A7A7, A10A10, A15 and A16 on TMV were 45.4%, 40.3%, 49.4% and 49.8%, respectively, which were superior to virazole (36.2%). In terms of protective activity, the inhibitory activities of compounds A _ (1) A _ (5) A _ (12) A _ (15) and A _ (16) on TMV were 58.5% (54.4N) 70.2 and 60.3%, respectively, which were superior to ribavirin (53.4%). In terms of passivation activity, the inhibitory activities of compounds A15 and A16 on TMV were 86.8 and 78.1, respectively, which were superior to virazole (77.3%). Further studies showed that the EC50 values of A3A10A15 and A16 for TMV were 274.8299.2251.8 and 287.7 渭 g / mL, respectively, which were better than that of ribavirin (379.8 渭 g/mL). In this paper, 17 compounds containing quinazoline-4 (3H) -ketone were designed and synthesized. The inhibitory activity of the compounds to TMV at a concentration of 500 渭 g/mL was tested. The results of bioactivity test showed that this series of compounds had good inhibitory activity to TMV. In terms of therapeutic activity, the inhibitory activities of compounds B3OB4OB5OB10B11 and B16 on TMV were 55.9% and 54.6%, respectively, which were better than those of Ningnanmycin (51.8%). In terms of protective activity, the inhibitory activities of compounds B _ (3) B _ (10) and B _ (11) on TMV were 69.8% and 72.0%, respectively, which were superior to those of Ningnanmycin (65.7%). Further studies showed that the EC50 values of compound B _ 3N _ (10) and B _ (11) for TMV were 138.5132.9 and 125.6 渭 g / mL, respectively, which were superior to those of Ningnanmycin (207.2 渭 g/mL). Five monopentadiene-3-ketoxime ethers containing coumarin were designed and synthesized. The inhibitory activity of these compounds against TMV at a concentration of 500 渭 g/mL was tested by half-leaf spot method and virazole as control. The results of bioactivity test showed that this series of compounds had moderate inhibitory activity to TMV. The inhibitory activities of C _ 3C _ 4 and C _ 5 on TMV were 38.9% and 42.5 respectively, which were better than that of ribavirin (36.2%). The inhibitory activities of some compounds against bacterial blight of rice and tobacco bacterial wilt were tested by turbidimetric method and commercial fungicide, leaf kudazole, at mass concentration of 100 渭 g / mL and 50 渭 g / mL, respectively. The results showed that the inhibitory activity of this series against the above two bacteria was relatively low at the concentration of 100 渭 g/mL and 50 渭 g/mL.
【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】：O626;TQ450.1
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