氮杂Brazilin-咪唑盐杂合物的设计、合成及细胞毒活性研究
收稿日期: 2014-12-31
修回日期: 2015-01-26
网络出版日期: 2015-02-05
基金资助
长江学者和创新团队发展计划(No. IRT13095)、国家自然科学基金(Nos. 21462049, 21332007, U1402227)、云南省自然科学基金(Nos. 2013FA028, 2012FB113, 2010GA014)资助项目.
Design, Synthesis and Cytotoxic Activity of Novel Hybrid Compounds between Aza-brazilin and Imidazolium
Received date: 2014-12-31
Revised date: 2015-01-26
Online published: 2015-02-05
Supported by
Project supported by the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT13095), the National Natural Science Foundation of China (Nos. 21462049, 21332007, U1402227), and the Natural Science Foundation of Yunnan Province (Nos. 2013FA028, 2012FB113, 2010GA014).
从3,4-二甲氧基苯丙酸出发合成了一系列新型的氮杂Brazilin-咪唑盐杂合物, 其结构经1H NMR, 13C NMR, HR-ESI-MS以及X射线单晶衍射确定. 对合成的新化合物进行了体外抗肿瘤活性筛选, 发现3-(萘-2-甲基)-1-(2-氧代- 2-(4,9,10-三甲氧基-6,6a,7,11b-四氢茚并[2,1-c]喹啉-5-基)乙基)-2-甲基苯并咪唑溴盐(26)具有较好的细胞毒活性, 对4种肿瘤细胞株的活性均优于顺铂, 特别是对HL-60、MCF-7和SW-480表现出较好的和选择性的细胞毒活性.
关键词： 氮杂Brazilin; 咪唑; 杂合物; 细胞毒活性
汪学全 , 李艳 , 羊晓东 , 张洪彬 . 氮杂Brazilin-咪唑盐杂合物的设计、合成及细胞毒活性研究[J]. 有机化学, 2015 , 35(6) : 1276 -1285 . DOI: 10.6023/cjoc201412055
A series of novel hybrid compounds between aza-brazilin and imidazole have been prepared from 3-(3,4-dimeth- oxyphenyl)propanoic acid. Their structures were confirmed by 1H NMR, 13C NMR, HR-ESI-MS and X-ray crystallographic analysis. These compounds have been evaluated in vitro against a panel of human tumor cell lines. 2-Methyl-3-(naphthalen- 2-ylmethyl)-1-(2-oxo-2-(4,9,10-trimethoxy-6,6a,7,11b-tetrahydro-5H-indeno[2,1-c]quinolin-5-yl)ethyl)-1H-benzo[d]imidazol- 3-ium bromide (26) was found to be the most potent derivative against four strains human tumor lines and more active than cisplatin, and exhibited the most potent cytotoxic activities selectively against HL-60, MCF-7 and SW-480.
Key words： aza-brazilin; imidazole; hybrid compound; cytotoxic activity
[1] Pan, C. X.; Guan, Y. F.; Zhang, H. B. Chin. J. Org. Chem. 2012, 32, 1116 (in Chinese). (潘成学, 关一富, 张洪彬, 有机化学, 2012, 32, 1116.)
[2] Robinson, R. Bull. Soc. Chim. Fr. 1958, 125.
[3] Kim, B. H.; Kim, S. J.; Jeong, E. J.; Sohn, J. H.; Jung, M.; Lee, H.; Kim, S. H. J. Agric. Food Chem. 2012, 60, 9882.
[4] (a) Kim, S. G.; Kim, Y. M.; Khil, L. Y.; Jeon, S. D.; So, D. S.; Moon, C. H.; Moon, C. K. Arch. Pharm. Res. 1998, 21, 140. (b) Hwang, G. S.; Kim, J. Y.; Chang, T. S.; Jeon, S. D.; So, D. S.; Moon, C. K. Arch. Pharm. Res. 1998, 21, 774.
[5] Hikino, H.; Taguchi, T.; Fujimura, H.; Hiramatsu, Y. Planta Med. 1977, 31, 214.
[6] Xu, H. X.; Lee, S. F. Phytother. Res. 2004, 18, 647.
[7] Pan, C. X.; Zeng, X. H.; Guan, Y. F.; Jiang, X. L.; Li, L.; Zhang, H. B. Synlett 2011, 425.
[8] (a) Vlahakis, J. Z.; Lazar, C.; Crandall, I. E.; Szarek, W. A. Bioorg. Med. Chem. 2010, 18, 6184. (b) Dominianni, S. J.; Yen, T. T. J. Med. Chem. 1989, 32, 2301. (c) Pardin, C.; Schmitzer, A. R.; Leclercq, L. Chem. Eur. J. 2010, 16, 4686.
[9] (a) Fortuna, C. G.; Barresi, V.; Berellini, G..; Musumarra, G. Bioorg. Med. Chem. 2008, 16, 4150. (b) Saberi, M. R.; Vinh, T. K.; Yee, S. W.; Griffiths, B. J. N.; Evan, P. J.; Simsons, C. J. Med. Chem. 2006, 49, 1016.
[10] (a) Jnr, C. V.; Danuello, A.; Bolzani, V. S.; Barreiro, E. J.; Fraga, C. A. M. Curr. Med. Chem. 2007, 14, 1829. (b) Walsh, J. J.; Bell, A. Curr. Pharm. Des. 2009, 15, 2970. (c) Zhu, P. F.; Zhao, J. F.; Yang, X. D.; Zhang, H. B. Chin. J. Org. Chem. 2014, 34, 1167 (in Chinese). (朱培芳, 赵静峰, 羊晓东, 张洪彬, 有机化学, 2014, 34, 1167.)
[11] CCDC 1041451 contains the supplementary crystallographic data for compound 22.These data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam. ac.uk/data_request/cif.
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