某些B-降胆甾噻唑化合物的合成及抗肿瘤活性研究
收稿日期: 2015-12-23
修回日期: 2016-03-05
网络出版日期: 2016-03-25
基金资助
国家自然科学基金（No.2146209）和广西高校北部湾石油天然气资源有效利用重点实验室开放课题（No.2014KLOG09）资助项目.
Synthesis and Evaluation of Some New B-Norcholesteryl Thiazole Compounds as Anticancer Agents
Received date: 2015-12-23
Revised date: 2016-03-05
Online published: 2016-03-25
Supported by
Project supported by the National Natural Science Foundation of China (No. 21462009) and the Guangxi Colleges and University Key Laboratory Foundation of Beibu Gulf Oil and Natural Gas Resoure Effective Utilization (No. 2014KLOG09).
从胆甾醇出发，合成了系列B-降胆甾烷噻唑化合物，通过IR、NMR及HRMS等现代分析方法对合成物进行了结构表征. 同时，分别采用人肺癌细胞（A549）、宫颈癌细胞（HeLa）、肝癌细胞（HEPG2）和人正常肾上皮细胞（HEK293T）对合成产物进行体外抑制肿瘤细胞增殖活性研究，结果表明具有N-甲基噻唑结构的化合物14和17对A549和HEPG2细胞的生长增殖表现出较好的抑制活性； 具有N-苯基噻唑结构的化合物20~24对HeLa细胞表现出选择性的增殖抑制作用，但对人正常肾上皮细胞却几乎没有作用.
关键词： 胆甾醇; 甾体杂环化合物; B-降甾体噻唑化合物; 抗肿瘤活性
黄燕敏 , 戚斌斌 , 崔建国 , 甘春芳 , 杨春晖 , 刘畅 , 陈爽 , 石海信 . 某些B-降胆甾噻唑化合物的合成及抗肿瘤活性研究[J]. 有机化学, 2016 , 36(7) : 1602 -1610 . DOI: 10.6023/cjoc201512031
Some B-norcholesteryl thiazole compounds were synthesized and their structures were determined by IR, NMR and HRMS. The antiproliferative activity of the compounds against human lung carcinoma (A549), cervical carcinoma (HeLa), liver carcinoma (HEPG2) and normal kidney epithelial (HEK293T) cells was assayed. The results showed that some compounds with a structure of N-methylthiazole showed distinct antiproliferative activity against A549 and HEPG2 cells. The compounds with a structure of N-phenylthiazole displayed a selective antiproliferative activity against HeLa cells and were almost inactive to HEK293T cells. The research provided a theoretical reference for the exploration of new anti-cancer agents.
[1] Luigio, T.; Saverio, F.; Catia, G. Steroids 2002, 67, 687.
[2] Mohared, R. M.; Elmegged, G. A.; Abdel-Salam, O. M. E.; Doss, S. H.; William, M. G. Steroid 2011, 76, 1190.
[3] Natalija, M.; Krsti?, N. M.; Mira, S.; Bjelakovi?, M. S.; Vladimir, D.; Pavlovi?, V. D. Steroids 2012, 77, 558.
[4] Mohared, R. M.; Al-Omran, F. Steroids 2012, 77, 1551.
[5] Festi, D.; Montagnani, M.; Azzaroli, F.; Lodato, F.; Mazzella, G.; Roda, A. Curr. Clin. Pharmacol 2007, 2(2), 155.
[6] Chen, S.-J.; Cui, J.-G.; Li, Y.; Fan, L.-H. Chin. J. Org. Chem. 2011, 31, 187 (in Chinese). (陈思静, 崔建国, 李莹, 范良华, 有机化学, 2011, 31, 187.)
[7] Zhang, X.-J.; Cui, J.-G.; Li, Y.; Chen, S.-J. Chin. J. Org. Chem. 2010, 30, 655 (in Chinese). (张晓佳, 崔建国, 李莹, 陈思静, 有机化学, 2010, 30, 655.)
[8] Traf, D. T. P. Cancer Lett. 2006, 243, 202.
[9] John, W. B.; Brent, R. C.; Robert, A. K.; Murray, H. G. M.; Michèle, R. P. Nat. Prod. Rep. 2013, 30, 237.
[10] John, W. B.; Brent, R. C.; Robert, A. K.; Murray, H. G. M.; Michèle, R. P. Nat. Prod. Rep. 2014, 31, 160.
[11] John, W. B.; Brent, R. C.; Robert, A. K.; Murray, H. G. M.; Michèle, R. P. Nat. Prod. Rep. 2015, 32, 116.
[12] Jorge, A. R. S.; João, F. S. C.; Marco, A. C. N.; Samuel, M. S.; Alcino, J. L.; Manuel, C. S.; Luisa, S. M. Nat. Prod. Rep. 2013, 30, 324.
[13] Wentworth, P.; Nieva, J.; Takeuchi, C.; Galve, R.; Wentworth, A. D.; Dilley, R. B.; DeLaria, G. A.; Saven, A.; Babior, B. M.; Janda, K. D.; Eschenmoser, A.; Lerner, R. A. Science 2003, 302, 1053.
[14] Wang, H. L.; Fang, J. M.; Cheng, Y. S. Phytochemistry 1998, 48, 1391.
[15] Miyamoto, T.; Kodama, K.; Aramaki, Y.; Higuchi, R.; Soest, R. W. M. Tetrahedron Lett. 2001, 42, 6349.
[16] Wei, X. M.; Rodriguez, A. D.; Wang, Y. H.; Franzblau, S. G. Tetrahedron Lett. 2007, 48, 8851.
[17] Wei, X. M.; Rodriguez, A. D.; Wang, Y. H.; Franzblau, S. G. Bioorg. Med. Chem. Lett. 2008, 18, 5448.
[18] Gan, C. F.; Fan, L. H.; Cui, J. G.; Huang, Y. M.; Jiao, Y. X.; Wei, W. X. Steroids 2012, 77, 1061.
[19] Gan, C. F.; Fan, L. H.; Huang, Y. M.; Liu, Z. P.; Cui, J. G. Med. Chem. 2013, 9, 846.
[20] Gan, C. F.; Lin, Q. F.; Cui, J. G.; Feng, J, D.; Guo, J. N.; Liao, H. Y.; Huang, Y. M. Steroids 2014, 79, 37.
[21] Singh, H.; Kapoor, V. K.; Paul, D. In Progress in Medicinal Chemistry, Vol. 16, Eds.: Ellis, G. P.; West, G. B., Springer, Amsterdam, 1979, pp. 35~150.
[22] Singh, H.; Jindal, D. P.; Yadav, M. R.; Kumar, M. In Progress in Medicinal Chemistry, Vol. 28, Eds.: Ellis, G. P.; West, G. B., Elsevier Science Publishers, Amsterdam, 1991, pp. 233~300.
[23] Cui, J. G.; Liu, L.; Gan, C. F.; Xiao, Q.; Huang, Y. M. Prog. Chem. 2014, 26(2/3), 320 (in Chinese). (崔建国, 刘亮, 甘春芳, 肖琦, 黄燕敏, 化学进展, 2014, 26(2/3), 320.)
[24] Ma, B.; Xiao, Z. Y.; Chen, Y. J.; Lei, M.; Meng, Y. H.; Guo, D. A.; Liu, X.; Hu, L. H. Steroids 2013, 78, 508.
[25] Guo, H.; Zhang, G. L.; Zhang, T.; He, X. R.; Wu, Z. Y.; Xiao, Y. L.; Pan, Y. H.; Qiu, G. F.; Liu, P.; Hu, X. M. Eur. J. Med. Chem. 2011, 46, 3662.
[26] Huang, L. H.; Zheng, Y. F.; Lu, Y. Z.; Song, C. J.; Wang, Y. G.; Yu, B.; Liu, H. M. Steroids 2012, 77, 710.
[27] Kovács, D.; Mótyán, G.; Wölfling, J.; Kovács, I.; Zupkó, I.; Frank, É. Bioorg. Med. Chem. Lett. 2014, 24, 1265.
[28] Zhang, B. L.; Zhang, E.; Pang, L. P.; Song, L. X.; Li, Y. F.; Yu, B.; Liu, H. M. Steroids 2013, 78, 1200.
[29] Cui, J. G.; Qi, B. B.; Gan, C. F.; Liu, Z. P.; Huang, H.; Lin, Q. F.; Zhao, D. D.; Huang, Y. M. Mar. Drugs 2015, 13, 2488.
[30] Lesyk, R.; Zimenkovsky, B.; Atamanyuk, D.; Jensen, F.; Kononowicz, K. K.; Gzella, A. Bioorg. Med. Chem. 2006, 14, 5230.
[31] Kashfi, K. Adv. Pharmacol. 2009, 57, 31.
[32] Ramla, M. M.; Omar, M. A.; El-Khamry, A. M.; El-Diwan, H. I. Bioorg. Med. Chem. 2006, 14, 7324.
[33] Sun, L. P.; Jiang, Z.; Gao, L. X.; Liu, X. F.; Quan, Y. C.; Zheng, G. H.; Li, J.; Piao, H. Chin. J. Org. Chem. 2013, 33, 1496.
[34] Mohareb, R. M.; Al-Omran, F. Steroids 2012, 77, 1551.
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