2-去氢表雄酮苯亚甲基衍生物的合成及抗炎活性研究

doi:10.6023/cjoc201901039

有机化学 ›› 2019, Vol. 39 ›› Issue (9): 2625-2631.DOI: 10.6023/cjoc201901039 上一篇下一篇

研究论文

2-去氢表雄酮苯亚甲基衍生物的合成及抗炎活性研究

朱丽^a,b, 杨艳秋^c, 高佩佩^a,b, 安雪^a,b, 孙莹莹^a,b, 孙晓雯^a,b, 侯悦^c, 单丽红^a,b

a 郑州大学药学院郑州 450001;
b 新药创制与药物安全性评价河南省协同创新中心郑州 450001;
c 东北大学生命科学与健康学院沈阳 110819

收稿日期:2019-01-25 修回日期:2019-03-22 发布日期:2019-04-11
通讯作者: 侯悦, 单丽红 E-mail:shlh@zzu.edu.cn;houyue@mail.neu.edu.cn
基金资助:
国家自然科学基金（Nos.21402178，U1603125）和河南省科学研究基金（No.132300410195）资助项目.

Synthesis and Anti-inflammatory Activity Evaluation of 2-Dehydroepiandrosterone Benzene Methyl Derivatives

Zhu Li^a,b, Yang Yanqiu^c, Gao Peipei^a,b, An Xue^a,b, Sun Yingying^a,b, Sun Xiaowen^a,b, Hou Yue^c, Shan Lihong^a,b

a School of Pharmaceutical Sciences, Zhengzhou 450001;
b Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001;
c College of Life and Health Sciences, Northeastern University, Shenyang 110819

Received:2019-01-25 Revised:2019-03-22 Published:2019-04-11
Contact: 10.6023/cjoc201901039 E-mail:shlh@zzu.edu.cn;houyue@mail.neu.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 21402178, U1603125) and the Scientific Research Fund of Henan Province (No. 132300410195).

文章分享

1. 2-去氢表雄酮苯亚甲基衍生物的合成及抗炎活性研究.PDF(1693KB)

摘要/Abstract

阿尔茨海默症作为21世纪全球主要健康危机之一，由于其发病机制的复杂性，目前还未找到很好的解决办法.为了找到更加经济有效的治疗神经退行性疾病的药物，合成了一系列新型2-去氢表雄酮苯亚甲基衍生物，并研究了其对脂多糖（LPS）激活小胶质细胞株BV-2 NO释放及细胞存活率的影响.结果表明所合成化合物作用24 h后，对LPS活化的小鼠小胶质细胞株BV2的NO释放均有不同程度的抑制作用，且具有一定的浓度依赖性.活性最好的化合物15β，16β-亚甲基雄甾-2-（3-氯）-苯亚甲基-4，6-二烯-3，17-二酮（5a）和15β，16β-亚甲基雄甾-2-（3，4，5-三甲氧基）-苯亚甲基-4，6-二烯-3，17-二酮（5j）的IC₅₀值分别为2.69和3.28 μmol·L^-1，优于阳性对照米诺环素.此类化合物在涉及活化小胶质细胞的神经退行性疾病方面的作用值得进一步研究.

关键词: 去氢表雄酮, 查尔酮类似物, 阿尔茨海默症, 小胶质细胞

Alzheimer's Disease (AD) is one of the major health crises in the 21st century, and due to the complexity of its pathogenesis, there has no good solution to cure this disease. In order to find more economical and effective drugs for the treatment of neurodegenerative diseases, a series of novel 2-dehydroepiandrosterone benzathine derivatives were synthesized and their activity on the NO release of microglia cell line BV-2 activated by lipopolysaccharide (LPS), as well as their effect on cell viability were studied. The structures of the synthesized compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. The results showed that all compounds had inhibitory effects on the NO release of LPS-activated mouse microglial cell line BV2 after 24 h of treatment, and it was dose-dependent. In particular, the IC₅₀ values of 2-(3-chloro)benzylidene-15β,16β-methylene-androstane-4,6-diene-3,17-dione (5a) and 2-(3,4,5-trimethoxy)benzylidene-15β,16β-methylene-androstane-4,6-die-ne-3,17-dione (5j) were 2.69 and 3.28 μmol·L^-1, respectively, which were better than the positive control Minocycline. The results showed that these compounds may be effective in the development of neurodegenerative diseases involving activation of microglia, and the mechanism deserved further study.

Key words: dehydroepiandrosterone, chalcone analogue, alzheimer's disease, microglia

引用此文

朱丽, 杨艳秋, 高佩佩, 安雪, 孙莹莹, 孙晓雯, 侯悦, 单丽红. 2-去氢表雄酮苯亚甲基衍生物的合成及抗炎活性研究[J]. 有机化学, 2019, 39(9): 2625-2631.

Zhu Li, Yang Yanqiu, Gao Peipei, An Xue, Sun Yingying, Sun Xiaowen, Hou Yue, Shan Lihong. Synthesis and Anti-inflammatory Activity Evaluation of 2-Dehydroepiandrosterone Benzene Methyl Derivatives[J]. Chin. J. Org. Chem., 2019, 39(9): 2625-2631.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

参考文献

[1] Lai, L. M.; Ling, C. X.; Zhang, X. F.; Hu, C. H. J. Shangqiu Teach. Coll. 2018, 34, 27(in Chinese). (来兰梅, 凌翠霞, 张向飞, 胡春华, 商丘师范学院学报, 2018, 34, 27.)
[2] (a) Barger, S. W.; Harmon, A. D. Nature 1997, 388, 878.
(b) Chang, J. Y.; Chavis, J. A.; Liu, L. Z.; Drew, P. D. BiochemBiophys. Res. Commun. 1998, 249, 817.
[3] (a) Carlier, P. R.; Chow, E. S.-H.; Han, Y.; Liu, J.; Yazal, J. E.; Pang, Y.-P. J. Med. Chem. 1999, 42, 4225.
(b) Li, L.; Yan, L.; Xiao, M. Q.; Zhong, C. C.; Rui, X.; Gan, Y. X.; Qing, S.; Zheng, H. T.; Yong, D. Bioorg. Med. Chem. 2017, 25, 1997.
[4] (a) Scherbakov, A. M.; Zavarzin, I. V.; Vorontsova, S. K.; Alakanada, H.; Andreeva, O. E.; Yadykov, A. V.; Levina, I. S.; Volkova, Y. A.; Shirinian, V. Z. Steroids 2018, 138, 91.
(b) Bano, S.; Javed, K.; Ahmad, S.; Rathish, I. G.; Singh, S.; Chaitanya, M.; Arunasree, K. M.; Alam, M. S. Eur. J. Med. Chem. 2013, 65, 51.
(c) Liu, H. R.; Zhou, C.; Fan, H. Q.; Tang, J. J.; Liu, L. B.; Gao, X. H.; Wang, Q. A.; Liu, W. K. Chem. Biol. Drug Des. 2015, 86, 517.
[5] Ren, S. T.; Wang, L.; Wu, Y. R.; Liu, X. J.; Wang, Y. X.; Liu, S. H. J. Huaihai Inst. Technol. (Nat. Sci. Ed.) 2018, 27, 32(in Chinese). (任抒婷, 王蕾, 吴煜然, 刘玮炜, 刘秀坚, 王有宪, 刘书豪, 淮海工学院学报(自然科学版), 2018, 27, 32.)
[6] (a) Zhang, X.; Rakesh, K. P.; Bukhari, S. N. A.; Balakrishna, M.; Manukumar, H. M.; Qin, H. L. Bioorg. Chem. 2018, 80, 86.
(b) Lahtchev, K. L.; Batovska, D. I.; Parushev, S. P.; Ubiyvovk, V. M.; Sibirny, A. A. J. Med. Chem. 2008, 43, 2220.
[7] Zhou, L.; Ren, M. L. Int. J. Geriatr. 2003, 24, 256(in Chinese). (周璘, 任慕兰, 国际老年医学杂志, 2003, 24, 256.)
[8] Schverer, M.; Lanfumey, L.; Baulieu, E.-E.; Froger, N.; Villey, I. Pharmacol. Ther. 2018, 191, 190.
[9] Shan, L. H.; Liu, H. M.; Jiang, D. D.; Zhao, S. S.; Qiao, X.; Zhang, L. J. CN 106591155, 2017.
[10] Romano, A.; Romano, D.; Ragg, E.; Costantinoc, F.; Lennac, R.; Gandolfid, R.; Molinaria, F. Steroids 2006, 71, 429.
[11] Walter, C.; Fablo, B.; Marco, A.; Manuela, R.; Clinzia, B. EP 1903051, 2008.

2-去氢表雄酮苯亚甲基衍生物的合成及抗炎活性研究

Synthesis and Anti-inflammatory Activity Evaluation of 2-Dehydroepiandrosterone Benzene Methyl Derivatives

PDF

补充材料

可视化

摘要/Abstract

引用此文

分享此文

参考文献

相关文章 4

编辑推荐

相关统计

本文评价

[1]	黄达涯, 李佑智, 刘艳, Bernard Meunier. 8-氨基喹啉类铜离子螯合剂的合成及螯合选择性研究[J]. 有机化学, 2019, 39(2): 500-506.
[2]	崔建国, 赵丹丹, 何冬梅, 黄燕敏, 刘志平, 林啟福, 石海信, 甘春芳. 去氢表雄酮噻唑衍生物的合成及抗肿瘤活性评估[J]. 有机化学, 2016, 36(3): 630-637.
[3]	黄燕敏, 刘亮, 戚斌斌, 赵丹丹, 杨雷, 甘春芳, 崔建国. 7β-羟基表雄酮的选择性合成[J]. 有机化学, 2015, 35(1): 241-245.
[4]	刘丰良,李元建,黄可龙,阳卫军. 乙二醛缩双(邻氨基苯酚)合锰(II)配合物的合成及其催化行为研究[J]. 有机化学, 2007, 27(9): 1106-1109.