含喹喔啉杨梅素衍生物的合成及生物活性
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摘要
利用活性拼接原理,将喹喔啉引入到杨梅素结构中,合成了一系列含喹喔啉基团的杨梅素新型衍生物.采用浊度法测试了目标化合物的体外抑菌活性,结果表明,目标化合物对柑橘溃疡病菌(X. Citri)和水稻白叶枯病菌(X. Oryzae)均表现出较好的抑制活性.目标化合物对柑橘溃疡病菌的抑制活性(EC50)均优于对照药叶枯唑和噻菌铜(EC50分别为54. 85和61. 13μg/m L),其中化合物4o抑制活性(EC50=11. 17μg/m L)最优;目标化合物对水稻白叶枯病菌的抑制活性EC50均优于对照药叶枯唑和噻菌铜(EC50分别为148. 20和175. 47μg/m L),其中化合物4f抑制活性(EC50=34. 49μg/m L)最优.采用半叶枯斑法测试了目标化合物的抗烟草花叶病毒(TMV)活性,结果表明,所有目标化合物在浓度为500 mg/L时均有一定的抑制作用.
According to the active substructure combination theory,a series of novel myricetin derivatives containing quinoxaline moieties was synthesized by introducing the quinoxaline blocks into the structures of myricetins. The antibacterial activities of the target compounds were evaluated via turbidimeter test in vitro. The preliminary bioassay results indicated that all of the title compounds exhibited certain antibacterial activities in vitro against Xanthomonas axonopodis pv. Citri(X. citri) and Xanthomonas oryzae pv. Oryzae(X. oryzae). The compounds were also tested to evaluate the half maximal effective concentration(EC50) of phytopathogenic bacteria. The results showed that all the X. citri EC50 of the target compounds were superior to those of the control drugs of bismerthiazol and thiodiazole copper(54. 85 and 61. 13 μg/m L,respectively). Compound 4 o(EC50= 11. 17 μg/m L) exhibited the best activity. All of the X. oryzae EC50 of the target compounds were superior to the control drugs of bismerthiazol and thiodiazole copper(148. 20 and 175. 47 μg/m L,respectively). Compound 4 f(EC50= 34. 49 μg/m L) exhibited the best activity. The in vivo efficacies against tobacco mosaic virus(TMV) of the target compounds were tested through half-leaf method. The results of bioassay showed that the target compounds exhibited certain anti-TMV activities at the concentration of 500 mg/L.
According to the active substructure combination theory,a series of novel myricetin derivatives containing quinoxaline moieties was synthesized by introducing the quinoxaline blocks into the structures of myricetins. The antibacterial activities of the target compounds were evaluated via turbidimeter test in vitro. The preliminary bioassay results indicated that all of the title compounds exhibited certain antibacterial activities in vitro against Xanthomonas axonopodis pv. Citri(X. citri) and Xanthomonas oryzae pv. Oryzae(X. oryzae). The compounds were also tested to evaluate the half maximal effective concentration(EC50) of phytopathogenic bacteria. The results showed that all the X. citri EC50 of the target compounds were superior to those of the control drugs of bismerthiazol and thiodiazole copper(54. 85 and 61. 13 μg/m L,respectively). Compound 4 o(EC50= 11. 17 μg/m L) exhibited the best activity. All of the X. oryzae EC50 of the target compounds were superior to the control drugs of bismerthiazol and thiodiazole copper(148. 20 and 175. 47 μg/m L,respectively). Compound 4 f(EC50= 34. 49 μg/m L) exhibited the best activity. The in vivo efficacies against tobacco mosaic virus(TMV) of the target compounds were tested through half-leaf method. The results of bioassay showed that the target compounds exhibited certain anti-TMV activities at the concentration of 500 mg/L.
引文
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[22] Xu W. M.,Han F. F.,He M.,Hu D. Y.,He J.,Yang S.,Song B. A.,J. Agric. Food Chem.,2012,60(4),1036—1041
[23] Chen Y.,Wang Z. B.,Zhang X.,Xia L. J.,Gong H. Y.,Zhao H. J.,Xue W.,Chin. J. Org. Chem.,2014,34(8),1662—1668(陈玉,王忠波,张贤,夏丽娟,龚华玉,赵洪菊,薛伟.有机化学,2014,34(8),1662—1668)
[2] Xu B. X.,Ding X. D.,Wu Y. C.,Cui L.,Qian P.,Wang D.,Zhao Y. F.,Chem. Res. Chinese Universities,2018,34(1),51—56
[3] Huang M. G.,Ruan X. H.,Zhang J. P.,Li Q.,Wang Y. H.,Chen L. J.,Zhang C.,Li P.,Xue W.,Chin. J. Org. Chem.,2017,37(8),2145—2152(黄民国,阮祥辉,张菊平,李琴,王一会,陈丽娟,张橙,李普,薛伟.有机化学,2017,37(8),2145—2152)
[4] Zhou J. R.,Mukheriee P.,Gugger E. T.,Tanaka T.,Blackbum G. L.,Clinton S. K.,Cancer Res.,1998,58(22),5231—5238
[5] Zhang X. J.,Huang Q. L.,Ji Y. B.,Tianjin Pharmacy,2008,20(5),57—60(张秀娟,黄清玲,季宇彬.天津药学,2008,20(5),57—60)
[6] Grenier D.,Chen H.,Ben L. A.,Fournier L. J.,Pierre M. M.,Plos One,2015,10(6),e0131758
[7] Yu M. S.,Lee J.,Lee J. M.,Kim Y.,Chin Y. W.,Jee J. G.,Keum Y. S.,Jeong Y. J.,Bioorg. Med. Chem. Lett.,2012,22(12),4049—4054
[8] Ruan X. H.,Zhao H. J.,Zhang C.,Chen L. J.,Li P.,Wang Y. H.,He M.,Xue W.,Chem. J. Chinese Universities,2018,39(6),1197—1204(阮祥辉,赵洪菊,张橙,陈丽娟,李普,王一会,贺鸣,薛伟.高等学校化学学报,2018,39(6),1197—1204)
[9] Liu I. M.,Tzeng T. F.,Liou S. S.,Lan T. W.,Planta Med.,2007,73(10),1054—1060
[10] Guo J. J.,Meng Y. H.,Zhao Y.,Hu Y. Y.,Rena D. Y.,Yang X. B.,Food Funct.,2015,6(5),1620—1634
[11] Shimmyo Y.,Kihara T.,Akaike A.,Niidome T.,Sugimoto H. J.,Neurosci. Res.,2008,86(6),1836—1845
[12] Xiao W.,Ruan X. H.,Li Q.,Zhang J. P.,Zhong X. M.,Xie Y.,Wang X. B.,Huang M. G.,Xue W.,Chem. J. Chinese Universities,2017,38(1),35—40(肖维,阮祥辉,李琴,张菊平,钟新敏,谢艳,王晓斌,黄民国,薛伟.高等学校化学学报,2017,38(1),35—40)
[13] Su X. W.,D’Souza D. H.,Food Environ. Virol.,2013,5(2),97—102
[14] Suguna M.,Kumar N. S.,Subbaiah M. V.,Krishnaiah A. J.,Chem. Pharm. Res.,2010,2(1),7—20
[15] Burguete A.,Pontiki E.,Hadjipavlou-Litina D.,Villar R.,Vicente E.,Solano B.,Ancizu S.,Pérez-Silanes S.,Aldana I.,Monge A.,Bioorg. Med. Chem. Lett.,2007,17(23),6439—6443
[16] Ganley B.,Chowdhury G.,Bhansali J.,Daniels J. S.,Gates K. S.,Bioorg. Med. Chem.,2001,9(9),2395—2401
[17] Rodrigues F. A.,Bomfim I. S.,Cavalcanti B. C.,Pessoa C..,Wardell J. L.,Wardell S. M.,Pinheiro A. C.,Kaiser C. R.,Nogueira T. C.,Low J. N.,Gomes L. R.,de Souza M. V.,Bioorg. Med. Chem. Lett.,2014,24(3),934—939
[18] Khan S. A.,Saleem K.,Khan Z.,Eur. J. Med. Chem.,2007,42(1),103—108
[19] Li Q.,Synthesis and Biological Activity of 1,4-Pentadien-3-one(oxime)Ether Compounds Containing Quinazoline(Quinoxaline)Groups,Guizhou University,Guiyang,2018(李琴.含喹唑(喔)啉基团的1,4-戊二烯-3-酮(肟)醚类化合物的合成及生物活性研究,贵阳:贵州大学,2018)
[20] Xue W.,Song B. A.,Zhao H. J.,Qi X. B.,Huang Y. J.,Liu X. H.,Eur. J. Med. Chem.,2015,97,155—163
[21] Li P.,Yin J.,Xu W. M.,Wu J.,He M.,Hu D. Y.,Yang S.,Song B. A.,Chem. Biol. Drug Des.,2013,82(5),546—556
[22] Xu W. M.,Han F. F.,He M.,Hu D. Y.,He J.,Yang S.,Song B. A.,J. Agric. Food Chem.,2012,60(4),1036—1041
[23] Chen Y.,Wang Z. B.,Zhang X.,Xia L. J.,Gong H. Y.,Zhao H. J.,Xue W.,Chin. J. Org. Chem.,2014,34(8),1662—1668(陈玉,王忠波,张贤,夏丽娟,龚华玉,赵洪菊,薛伟.有机化学,2014,34(8),1662—1668)