含喹唑啉硫醚的杨梅素衍生物的设计、合成及生物活性研究
收稿日期: 2020-08-07
修回日期: 2020-09-04
网络出版日期: 2020-10-12
基金资助
国家自然科学基金(21867003); 贵州省自然科学基金(20192452); 贵州省自然科学基金(20191105); 贵州省自然科学基金(20171028)
Design, Synthesis and Biological Activities of Myricetin Derivatives Containing Quinazoline Thioether Moiety
Received date: 2020-08-07
Revised date: 2020-09-04
Online published: 2020-10-12
Supported by
the National Natural Science Foundation of China(21867003); the Natural Science Foundation of Guizhou Province(20192452); the Natural Science Foundation of Guizhou Province(20191105); the Natural Science Foundation of Guizhou Province(20171028)
以杨梅苷为原料, 通过活性拼接, 设计并合成一系列含喹唑啉硫醚的杨梅素衍生物, 其结构通过1H NMR、13C NMR、19F NMR和HRMS进行确证. 生物活性测试结果表明, 该类化合物对水稻白叶枯病菌(X. Oryzae)、柑橘溃疡病菌(X. Citri)和烟草青枯病菌(R. Solanacearum)表现出一定的抑制活性. 其中, 5,7-二甲氧基-3-(3-((6-溴喹唑啉-4-基)硫基)丙氧基)-2-(3,4,5-三甲氧基苯基)-4H-色烯-4-酮(A15)对水稻白叶枯病菌的EC50值为13.9 μg/mL, 优于对照药叶枯唑(88.9 μg/mL)和噻菌铜(68.1 μg/mL); 5,7-二甲氧基-3-(4-((6-氯喹唑啉-4-基)硫基)丁氧基)-2-(3,4,5-三甲氧基苯基)-4H-色烯-4-酮(A3)、5,7-二甲氧基-3-(3-((6-氯喹唑啉-4-基)硫基)丙氧基)-2-(3,4,5-三甲氧基苯基)-4H-色烯-4-酮(A14)、5,7-二甲氧基- 3-(3-((6-溴喹唑啉-4-基)硫基)丙氧基)-2-(3,4,5-三甲氧基苯基)-4H-色烯-4-酮(A15)和5,7-二甲氧基-3-(3-((6-氟喹唑啉-4-基)硫基)丙氧基)-2-(3,4,5-三甲氧基苯基)-4H-色烯-4-酮(A16)对烟草青枯病菌的EC50值分别为1.1, 14.0, 11.9和7.5 μg/mL, 优于对照药叶枯唑(38.5 μg/mL)和噻菌铜(184.8 μg/mL). 活体实验结果表明, 化合物A15对水稻白叶枯病菌的具有良好治疗活性和保护活性. 通过扫描电镜成像初步探讨了目标化合物A3对烟草青枯病菌和A15对水稻白叶枯病菌的抑菌作用机制.
贺军 , 唐雪梅 , 周清 , 彭峰 , 刘婷婷 , 柳立伟 , 贺鸣 , 谢承卫 , 薛伟 . 含喹唑啉硫醚的杨梅素衍生物的设计、合成及生物活性研究[J]. 有机化学, 2021 , 41(2) : 708 -718 . DOI: 10.6023/cjoc202008006
A series of myricetin derivatives containing quinazoline thioether moiety were designed and synthesized using myricetrin as the starting material through active splicing strategy. All target compounds were characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. Their biological activities were evaluated. The results of biological activities showed that these compounds exhibited certain inhibitory activities against X. oryzae, X. citri and R. solanacearum. Among them, 3-(3-((6-bro- moquinazolin-4-yl)thio)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A15) displayed appreciable inhibitory effect against X. oryzae with a half maximal effective concentration (EC50) values of 13.9 μg/mL, which was better than those of the control drugs of bismerthiazol (88.9 μg/mL) and thiodiazole-copper (68.1 μg/mL). The EC50 values of 3-(4- ((6-chloroquinazolin-4-yl)thio)butoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A3), 3-(3-((6-chloro- quinazolin-4-yl)thio)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A14), 3-(3-((6-chloroquinazolin- 4-yl)thio)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A15) and 3-(3-((6-fluoroquinazolin-4-yl)- thio)propoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (A16) against Ralstonia solanacearum were 1.1, 14.0, 11.9 and 7.5 μg/mL, respectively, which were superior to the control drugs of bismerthiazol (38.5 μg/mL) and thio-diazole-copper (184.8 μg/mL). The results of in vivo experiments showed that compound A15 has good curative and protective activities against X. oryzae. The possible antibacterial mechanisms of target compound A3 against R. solanacearum and A15 against X. oryzae were preliminarily discussed base on scanning electron microscope analyses.
| [1] | Fan, Z.J.; Shi, J., Luo, N.; Ding, M.H.; Bao, X.P. J. Agric. Food Chem. 2019, 67, 11598. |
| [2] | Jiang, S.C.; Tang, X.; Chen, M.; He, J.; Su, S.J.; Liu, L.W.; Xue, W. Pest Manage. Sci. 2019, 76, 853. |
| [3] | Tang, X.; Zhang, C.; Chen, M.; Xue, Y.N.; Liu, T.T.; Xue, W. New J. Chem. 2020, 44, 2374. |
| [4] | Mo, F.; Ma, J.; Yang, X.; Zhang, P.; Li, Q.; Zhang, J. Phytomedicine 2020, 153223. |
| [5] | Yu, M.S.; Lee, J.; Lee, J.M.; Kim, Y.; Chin, Y.W.; Jee, J.G.; Jeong, Y.J. Bioorg. Med. Chem. Lett. 2012, 22, 4049. |
| [6] | Sun, F.; Zheng, X.Y.; Ye, J.; Wu, T.T.; Wang, J.L.; Chen, W. Nutr. Cancer 2012, 64, 599. |
| [7] | Afroze, N.; Pramodh, S.; Hussain, A.; Waleed, M.; Vakharia, K. 3 Biotech 2020, 10, 211. |
| [8] | Wang, S.J.; Tong, Y.; Lu, S.; Yang, R.; Liao, X.; Xu, Y.F.; Li, X. Planta Med. 2010, 76, 1492. |
| [9] | Jiang, M.; Zhu, M.; Wang, L.; Yu, S. Biomed. Pharmacother. 2019, 120, 109506. |
| [10] | Guitard, R.; Paul, J.F.; Véronique, N.R.; Aubry, J.M. Food Chem. 2016, 213. |
| [11] | Jiang, S.C.; Su, S.J.; Chen, M.; Peng, F.; Zhou, Q.; Liu, L.W.; Xue, W. J. Agric. Food Chem. 2020, 68, 5641. |
| [12] | Li, P. ; Chen, Y. ; Xia, R.J. ; Guo, T. ; Zhang, M. ; Jiang, S.C. ; Tang, X. ; He, M. ; Xue, W. Chem. J. Chin. Univ. 2019, 40, 909. (in Chinese) |
| [12] | 李普, 陈英, 夏榕娇, 郭涛, 张敏, 蒋仕春, 汤旭, 贺鸣, 薛伟, 高学校化学学报, 2019, 40, 909.). |
| [13] | Liu, H.B. ; Lv, P. ; Pan, N.N. ; Ai, L.M. ; Liu, Y.X. Chem. J. Chin. Univ. 2014, 35, 981. (in Chinese) |
| [13] | 刘海彬, 吕萍, 潘宁宁, 艾丽梅, 刘永祥, 高学校化学学报, 2014, 35, 981.). |
| [14] | Xu, Y.Y. M.S. Thesis, Suzhou University, Suzhou, 2014. (in Chinese) |
| [14] | 许芸芸, 硕士论文, 苏州大学, 苏州, 2014. ). |
| [15] | Zhang, G.Q. ; Guo, Q.Q. ; Zhao, T.Y. ; Wang, M. ; Xing, L.N. Chin. J. Synth. Chem. 2020, 28, 491. (in Chinese) |
| [15] | 张贵强, 郭晴晴, 易君明, 赵廷渊, 王梅, 邢林娜, 合成化学, 2020, 28, 491.). |
| [16] | Dos, R.; Sharon, V.; Ribeiro, N.S.; Rocha, D.A.; Fortes, I.S.; Silva, T.D.; Andrade, S.F.; Macedo, A.J. Chem. Biol. Drug Des. 2020. |
| [17] | Wan, Z.H. M.S. Thesis, Guizhou University, Guiyang, 2015 (in Chinese) |
| [17] | 万治华, 硕士论文, 贵州大学, 贵阳, 2015. ). |
| [18] | Sun, H.Y. ; Sun, H.S. ; Liu, M.Z. ; Huang, W. ; Yang, G.F. Chin. J. Org. Chem. 2018, 38, 2067. (in Chinese) |
| [18] | 孙海燕, 孙宏顺, 刘明珍, 黄伟, 杨光富, 有机化学, 2018, 38,2067. ). |
| [19] | Wu, J.; Bai, S.; Yue, M.; Luo, L.J.; Shi, Q.C.; Ma, J.; Du, X.L.; Kang, S.H.; Hu, D.Y.; Yang, S. Chem. Pap. 2014, 68, 969. |
| [20] | Gao, X.W. ; Cai, X.J. ; Yan, K. ; Gao, L.L. ; Wang, H.Y. ; Chen, Z. ; Song, B.A. Chin. J. Org. Chem. 2008, 28, 1785. (in Chinese) |
| [20] | 高兴文, 蔡学建, 严凯, 高丽丽, 王和英, 陈卓, 宋宝安, 有机化学, 2008, 28, 1785.). |
| [21] | Li, Q. M.S. Thesis, Guizhou University, Guiyang, 2018 (in Chinese) |
| [21] | 李琴, 硕士论文, 贵州大学, 贵阳, 2018. ). |
| [22] | Liu, J.H. ; Liu, Y. ; Jian, J.Y. ; Bao, X.P. Chin. J. Org. Chem. 2013, 33, 370. (in Chinese) |
| [22] | 刘军虎, 刘勇, 蹇军友, 鲍小平, 有机化学, 2013, 33, 370.). |
| [23] | Zhang, C.R. ; Wang, L. ; Ge, Y.L. ; Ju, X.L. Chin. J. Org. Chem. 2007, 27, 1432. (in Chinese) |
| [23] | 张成仁, 王柳, 葛燕丽, 巨修练, 有机化学, 2007, 27, 1432.). |
| [24] | Yang, Y. ; Ma, Y.N. ; Huang, T. ; Xie, W. ; Zhang, X. ; Huang, G.S. ; Liu, X.D. Chin. J. Org. Chem. 2018, 38, 2143. (in Chinese) |
| [24] | 杨锐, 马艳妮, 黄婷, 解伟, 张霞, 黄国双, 刘小东, 有机化学, 2018, 38, 2143.). |
| [25] | Xue, W.; Song, B.A.; Zhao, H.J; Qi, X.B.; Huang, Y.J.; Liu, X.H. Eur. J. Med. Chem. 2015, 97, 155. |
| [26] | Chen, Y.; Li, P.; Su, S.J.; Chen, M.; He, J.; Liu, L.W.; Xue, W. RSC Adv. 2019, 9, 23045. |
| [27] | Long, C.W. M.S. Thesis, Guizhou University, Guiyang, 2015 (in Chinese) |
| [27] | 龙承文, 硕士论文, 贵州大学, 贵阳, 2015. ). |
| [28] | Zhang, C. ; Jiang, S.C. ; Chen, Y. ; Guo, T. ; Xia, R.J. ; Tang, X. ; Chen, L.J. ; He, M. ; Xue, W. Chin. J. Org. Chem. 2019, 39, 1160. (in Chinese) |
| [28] | 张橙, 蒋仕春, 陈英, 郭涛, 夏榕娇, 汤旭, 陈丽娟, 贺鸣, 薛伟, 有机化学, 2019, 39, 1160.). |
| [29] | Wang, L.; Zhou, X.; Lu, H.; Mu, X.F.; Jin, L.H. Molecules 2020, 25, 1488. |
| [30] | Chen, Y. ; Li, P. ; Chen, M. ; Su, S.J. ; He, J. ; Zhang, M. ; Liu, L.W. ; Xue, W. Chin. J. Org. Chem. 2019, 39, 2813. (in Chinese) |
| [30] | 陈英, 李普, 陈梅, 苏时军, 贺军, 张敏, 柳立伟, 薛伟, 有机化学, 2019, 39, 2813.). |
/
| 〈 |
|
〉 |
