含吡啶的戊二烯酮肟醚類衍生物的合成及其生物活性研究
發(fā)布時間：2018-11-09 08:18
【摘要】：1,4-戊二烯-3-酮類化合物,作為一種重要的姜黃素衍生物,具有抑菌、抗腫瘤、抗氧化、抗炎、殺蟲、抗病毒和殺蟲等廣泛的生物活性,已成為藥劑創(chuàng)制工作中的熱點(diǎn)之一。近年來的研究發(fā)現(xiàn)此類化合物表現(xiàn)有明顯的抗植物病毒活性。同時,肟醚類化合物也具有高效、廣譜和作用方式較為獨(dú)特的特點(diǎn),在農(nóng)藥的創(chuàng)制過程中起到了重要的作用。鑒于此,我們將1,4-戊二烯-3-酮結(jié)構(gòu)中的羰基改變?yōu)殡棵呀Y(jié)構(gòu),設(shè)計合成了系列分子中分別含有吡啶、喹唑啉-4(3H)-酮和香豆素結(jié)構(gòu)的1,4-戊二烯-3-酮肟醚類化合物,所得化合物均通過了IR、1H NMR、13C NMR和HRMS或ESI-MS驗(yàn)證。本論文主要研究工作概括如下:1.設(shè)計合成了18個分子中含吡啶的1,4-戊二烯-3-酮肟醚類化合物,并采用半葉枯斑法,以病毒唑?yàn)閷φ账巹?測試了該系列化合物在質(zhì)量濃度為500μg/mL下對TMV的抑制活性。生物活性測試結(jié)果表明該系列化合物對TMV具有良好的抑制活性。在治療活性方面,化合物A1、A2、A3、A7、A8、A10、A15和A16對TMV的抑制活性分別為45.4、40.3、49.4、43.1、39.8、45.1、54.6和47.6%,優(yōu)于病毒唑(36.2%);在保護(hù)活性方面,化合物A1、A5、A12、A15和A16對TMV的抑制活性分別為58.5、54.4、59.9、70.2和60.3%,優(yōu)于病毒唑(53.4%);在鈍化活性方面,化合物A15和A16對TMV的抑制活性分別為86.8和78.1%,優(yōu)于病毒唑(77.3%)。進(jìn)一步的研究表明:化合物A3、A10、A15和A16對TMV治療活性的EC50值分別為274.8、299.2、251.8和287.7μg/mL,優(yōu)于病毒唑(379.8μg/mL)。2.設(shè)計合成了17個分子中含喹唑啉-4(3H)-酮的1,4-戊二烯-3-酮肟醚類化合物,并采用半葉枯斑法,以寧南霉素為對照藥劑,測試了該系列化合物在質(zhì)量濃度為500μg/mL下對TMV的抑制活性。生物活性測試結(jié)果表明該系列化合物對TMV具有良好的抑制活性。在治療活性方面,化合物B3、B4、B5、B10、B11和B16對TMV的抑制活性分別為55.9、53.4、54.6、55.4、59.1和53.5%,優(yōu)于寧南霉素(51.8%);在保護(hù)活性方面,化合物B3、B10和B11對TMV的抑制活性分別為69.8、67.7和72.0%,優(yōu)于寧南霉素(65.7%)。進(jìn)一步的研究表明:化合物B3、B10和B11對TMV治療活性的EC50值分別為138.5、132.9和125.6μg/mL,優(yōu)于寧南霉素(207.2μg/mL)。3.設(shè)計合成了5個分子中含香豆素的1,4-戊二烯-3-酮肟醚類化合物,并采用半葉枯斑法,以病毒唑?yàn)閷φ账巹?測試了該系列化合物在質(zhì)量濃度為500μg/mL下對TMV的抑制活性。生物活性測試結(jié)果表明該系列化合物對TMV具有中等程度的抑制活性。其中,在治療活性方面,化合物C3、C4和C5對TMV的抑制活性分別為38.9、38.8和42.5%,優(yōu)于病毒唑(36.2%)。4.采用濁度法,以商品化藥劑葉枯唑?yàn)閷φ账巹?測試了部分化合物在質(zhì)量濃度為100和50μg/m L下對水稻白葉枯病菌和煙草青枯病菌的體外抑制活性。初篩結(jié)果表明,該系列在藥劑濃度為100和50μg/mL下對以上兩種細(xì)菌的抑制活性相對較低。
[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.
【學(xué)位授予單位】：貴州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：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.
【學(xué)位授予單位】：貴州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O626;TQ450.1
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