去氢表雄酮噻唑衍生物的合成及抗肿瘤活性评估
收稿日期: 2015-09-18
修回日期: 2015-11-18
网络出版日期: 2015-11-26
基金资助
国家自然科学基金(Nos. 21462009, 21562007)、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)、合成与天然功能分子化学广西重点实验室资助项目.
Synthesis of Dehydroepiandrosteronyl Thiazole Derivatives and Their Antiproliferative Evaluation
Received date: 2015-09-18
Revised date: 2015-11-18
Online published: 2015-11-26
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 21462009, 21562007), the Key Laboratory Project of Effective Utilization of Petroleum and Natural Gas Resources in Guangxi Beibu Gulf (No. 2014KLOG09), and the Synthetic and Natural Functional Molecular Chemistry Lab of Guangxi.
以去氢表雄酮为原料, 通过微波一步合成法及常规2步合成方法合成得到16个新的具有不同结构特征的去氢表雄酮噻唑衍生物. 所有合成物都通过了IR、NMR及HRMS的结构表征. 另外, 分别选用人宫颈癌细胞(HeLa)、人肝癌细胞(HepG)、人肺癌细胞(A549)和人正常肾上皮细胞(HEK-293T)对合成物的抗肿瘤活性进行了研究, 结果表明4-(4'-三氟甲基)苯基噻唑-2-去氢表雄酮腙(4)对所测试的肿瘤细胞株具有很好的生长增殖抑制活性, 对上述肿瘤细胞的IC50值分别为13.2、11.3和8.3 μmol·L-1, 对人肾上皮正常细胞HEK-293T却没有表现出明显的抑制作用(IC50值>100 μmol·L-1). 但是, 其它合成物对所测试的细胞株没有表现出明显的抑制活性.
关键词： 去氢表雄酮; 噻唑; 去氢表雄酮噻唑衍生物; 抗肿瘤活性
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 . DOI: 10.6023/cjoc201509021
Using dehydroepiandrosterone as starting material, 16 dehydroepiandrosteronyl thiazol derivatives with different structures had been synthesized via microwave irradiation assisted one-pot reaction and general synthetic method, and their structures were characterized by IR, NMR and HRMS. The antiproliferative activity of the compounds was evaluated against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma cells (HEPG2) and normal kidney epithelial cells (HEK293T). The results showed that compound 4 displayed significant inhibitory activity to tested cancer cells, and the values of IC50 were 13.2, 11.3 and 8.3 μmol·L-1 respectively, but was almost inactive to HEK293T cells (IC50>100 μmol·L-1). However, other compounds did not exhibit distinct antiproliferative activity to all tested cells.
[1] Bansal, R.; Acharya, P. C. Chem. Rev. 2014, 114, 6986.
[2] Mohared, R. M.; Elmegged, G. A.; Abdel-Salam, O. M. E.; Doss, S. H.; William, M. G. Steroids 2011, 76, 1190.
[3] Krsti?, N. M.; Bjelakovi?, M. S.; Pavlovi?, V. D.; Robeyns, K.; Jurani?, Z. D.; Mati?, I.; Novakovi?, I.; Sladi?, D. M. Steroids 2012, 77, 558.
[4] Mohared, R. M.; Al-Omran, F. Steroids 2012, 77, 1551.
[5] Frank, E.; Schneider, G. J. Steroid Biochem. Mol. Biol. 2013, 127, 301.
[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] Cui, J.-G.; Liu, L.; Gan, C.-F.; Xiao, Q. 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.)
[10] Cui, S.-F.; Wang, Y.; Lü, J.-S.; Damu Guri, L. V. ; Zhou, C.-H. Sci. China, Ser B 2012, 42, 1105 (in Chinese). (崔胜峰, 王艳, 吕敬松, Damu Guri, L. V.; 周成合, 中国科学, 化学, 2012, 42, 1105.)
[11] Lesyk, R.; Zimenkovsky, B.; Atamanyuk, D.; Jensen, F.; Kononowicz, K. K.; Gzella, A. Bioorg. Med. Chem. 2006, 14, 5230.
[12] Kashfi, K. Adv. Pharmacol. 2009, 57, 31.
[13] Ramla, M. M.; Omar, M. A.; El-Khamry, A. M.; El-Diwan, H. I. Bioorg. Med. Chem. 2006, 14, 7324.
[14] 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 (in Chinese). (孙良鹏, 姜哲, 高立信, 刘晓芳, 全迎春, 郑光浩, 李佳, 朴虎日, 有机化学, 2013, 33, 1496.)
[15] Mohareb, R. M.; Al-Omran, F. Steroids 2012, 77, 1551.
[16] Yuan, M.-Y.; Liu, M.; Zhang, Y.-Q.; Yan, H.-F.; Li, D.-F.; Zhang, D. N.; Liu, H. M. Chin. J. Org. Chem. 2012, 32, 1746 (in Chinese). (袁明月, 刘敏, 张英群, 闫红飞, 李德富, 张冬暖, 刘卉闵, 有机化学, 2012, 32, 1746.)
[17] Chen, C.-J.; Song, B. A. Pesticide 2005, 44(2), 53 (in Chinese). (陈才俊, 宋宝安, 农药, 2005, 44(2), 53.)
[18] Shingate, B. B.; Hazra, B. G.; Salunke, D. B.; Pore, V. S.; Shirazi, F.; Deshpande, M. V. Eur. J. Med. Chem. 2011, 46, 3681.
[19] Cui, J.; Qi, B.; Gan, C.; Liu, Z.; Huang, H.; Lin, Q.; Zhao, D.; Huang. Y. Mar. Drugs 2015, 13, 2488.
[20] Cui, J.; Liu, L.; Zhao, D.; Gan, C.; Huang, X.; Xiao, Q.; Qi, B.; Yang, L.; Huang, Y. Steroids 2015, 95, 32.
[21] Zhao, D.-D.; Qi, B.-B.; Yang, L.; Huang, Y.-M.; Gan, C.-F.; Cui, J.-G. Chin. J. Med. Chem. 2014, 24, 470 (in Chinese). (赵丹丹, 戚斌斌, 杨雷, 黄燕敏, 甘春芳, 崔建国, 中国药物化学杂志, 2014, 24, 470.)
[22] Qi, B.-B.; Liu, L.; Zhao, D.-D; Yang, L.; Huang, Y. M.; Cui, J.-G. Chem. Res. Appl. 2015, 27, 665 (in Chinese). (戚斌斌, 刘亮, 赵丹丹, 杨雷, 甘春芳, 黄燕敏, 崔建国, 化学研究与应用, 2015, 27, 665.)
[23] Yang, S.; Fu, Z.-D.; Han, R. Acta Pharm. Sinica 2001, 36, 576 (in Chinese). (杨笋, 付招娣, 韩锐, 药学学报, 2001, 36, 576.)
[24] Ahluwalia, V. K.; Chibber, S. S.; Goyal, B. Indian J. Chem., Sect. B 1996, 35, 856.
[25] Yuan, M.-Y.; Liu, W. H.; Zhang, Y. Q.; Yan, H. F.; Zhang, D.-N.; Liu, H.-M.; Wang, J.-P. Chin. J. Org. Chem. 2013, 33, 1108 (in Chinese). (袁明月, 刘伟华, 张英群, 闫红飞, 张冬暖, 刘卉闵, 王建平, 有机化学, 2013, 33, 1108.)
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