具有肝靶向潜力的马蹄金素衍生物合成及抗乙肝活性研究
收稿日期: 2015-05-07
修回日期: 2015-06-08
网络出版日期: 2015-06-19
基金资助
国家自然科学基金(No. 81360472)和西部之光人才 (2014年)资助项目.
Synthesis and Anti-hepatitis B Virus Activities of Matijin-Su Derivatives with Potential for Hepatic Targeting
Received date: 2015-05-07
Revised date: 2015-06-08
Online published: 2015-06-19
Supported by
Project supported by the National Natural Science Foundation of China (No. 81360472) and the Western Light Talent Culture Project (2014).
袁洁 , 刘青川 , 徐广灿 , 胡占兴 , 梁光平 , 黄正明 , 刘昌孝 , 梁光义 , 徐必学 . 具有肝靶向潜力的马蹄金素衍生物合成及抗乙肝活性研究[J]. 有机化学, 2015 , 35(10) : 2176 -2183 . DOI: 10.6023/cjoc201505011
To improve the concentration in liver lesion tissue and increase the anti-hepatitis B virus (HBV) activity of Matijin-Su [N-(N-benzoyl-l-phenylalanyl)-O-acetyl-L-phenylalanol, MTS] derivatives, five galactosyl derivatives of MTS with potential for hepatic targeting were synthesized and their structures were confirmed by 1H NMR, 13C NMR, 1H-1H COSY, HMQC and ESI-MS. The anti-HBV activities of those compounds were evaluated in HepG2 2.2.15 cells. The screening results showed that all target compounds had inhibitory effect on HBV DNA replication in HepG2 2.2.15 cells in a dose-effect relationship.
[1] Pierre, V. D.; Zanetti, A. R.; Shouval, D.; Herck, K. V. Adv. Exp. Med. Biol. 2010, 659, 175.
[2] Xu, B.-X.; Huang, Z.-M.; Liu, C.-X.; Cai, Z.-G.; Pan, W.-D.; Cao, P.-X.; Hao, X.-J.; Liang, G.-Y. Bioorg. Med. Chem. 2009, 17, 3118.
[3] Qiu, J.-Y.; Xu, B.-X.; Huang, Z.-M.; Pan W.-D.; Cao P.-X.; Liu C.-X.; HaO, X.-J.; Song, B.-A.; Liang, G.-Y. Bioorg. Med. Chem. 2011, 19, 5352.
[4] Qiu, J.-Y.; Huang, Z.-M.; Pan, W.-D.; Cao, P.-X.; Liang, G.-Y. J. Chin. Pharm. Univ. 2012, 43, 390 (in Chinese).(邱净英, 黄正明, 潘卫东, 曹佩雪, 梁光义, 中国药科大学学报, 2012, 43, 390.)
[5] Liang, G.-P.; Cao, P.-X.; Yang, X.-X.; Huang, Z.-M.; Liu Q.-C.; Liang, G.-Y.; Xu, B.-X. Chin. J. Org. Chem. 2014, 34, 973 (in Chinese).(梁光平, 曹佩雪, 杨秀虾, 黄正明, 刘青川, 梁光义, 徐必学, 有机化学, 2014, 34, 973.)
[6] Spiess, M. Biochemistry 1990, 29, 10009.
[7] Zhu, J.-Q.; Chen, H.; Wang, S.-R.; Li, Y.; Fang, W.-S. Chem. J. Chin. Univ. 2013, 34, 1660 (in Chinese).(朱建勤, 陈晖, 王少戎, 李燕, 方唯硕, 高等学校化学学报, 2013, 34, 1660.)
[8] Huang, Z.-J.; Zhang, Y.-H.; Zhao, L.; Jing, Y.-W.; Lai, Y.-S.; Zhang, L.-Y.; Guo, Q.-L.; Yuan, S.-T.; Zhang, J.-J.; Chen, L.; Peng, S.-X.; Tian, J.-D. Org. Biomol. Chem. 2010, 8, 632.
[9] Huang, Z.-J.; Fu, J.-J.; Liu, L.; Sun, Y.-J.; Lai Y.-S.; Ji, H.; Kanus, E. E.; Tian, J.-D.; Zhang, Y.-H. Org. Biomol. Chem. 2012, 10, 3882.
[10] Krikor, B. J.; Zhang, Z.-W.; Xu, B.; Su, J.; Chen, B.; Wan, S.-B.; Wu, J.-H.; Jiang, T.; Moulay A, A. J. Eur. J. Med. Chem. 2012, 48, 143.
[11] Tsukida, T.; Moriyama, H.; Kurokawa, K.; Achiha, T.; Inoue, Y.; Kondo, H. J. Med. Chem. 1998, 41, 4279.
[12] Jain, R. K.; Locke, R. D.; Matta, K. L. Carbohydr. Res. 1993, 241, 165.
[13] Felpin, F. X.; Boubekeur, K.; Lebreton, J. J. Org. Chem. 2004, 69, 1497.
[14] Chuang, H.-Y.; Ren, C.-T.; Chao, C.-A.; Wu, C.-Y.; Shivatare, S. S.; Cheng, T. J.; Wu, C.-Y.; Wong, C. H. J. Am. Chem. Soc. 2013, 135, 11140.
[15] Nicolaou, K. C.; Seitz, S. P.; Papahatjis, D. P. J. Am. Chem. Soc. 1983, 105, 2430.
[16] Yao, N.-H.; He, W.-Y.; Lam, K. S.; Liu, G. J. Comb. Chem. 2004, 6, 214.
[17] Ishida, H.; Ando, H.; Ito, H.; Kiso, M.; Hasegawa, A. J. Carbohydr. Chem. 1997, 16, 413.
[18] Greene, T. W.; Wuts, P. G. M. In Protective Groups in Organic Synthesis, John Wiley & Sons, Inc, New York, 1999, p. 564.
[19] Carocci, A.; Catalano, A.; Corbo, F.; Duranti, A.; Amoroso, R.; Franchini, C.; Lentini, G.; Tortorella, V. Tetrahedron: Asymmetry 2000, 11, 3619.
[20] Chen, N.; Xie, J. J. Org. Chem. 2014, 79, 10716.
[21] Cai, M.-S.; Li, Z.-J. In Carbohydrate Chemistry: Fundamentals, Reactions, Synthesis, Isolation and Structure., Chemical Industry Press, Beijing, 2006, p. 370 (in Chinese).(蔡孟深, 李中军, 糖化学——基础、反应、合成、分离及结构,化学工业出版社, 北京, 2006, p. 370.)
[22] Pathigoolla, A.; Sureshan, K. M. Chem. Commun. 2014, 50, 317.
[23] Nasopolou, M.; Georgiadis, D.; Matziari, M.; Dive, V.; Yiotakis, A. J. Org. Chem. 2007, 72, 7222.
/
| 〈 |
|
〉 |
