山荷叶素异羟肟酸和硫醇衍生物的合成与抑制肿瘤细胞增殖活性
收稿日期: 2012-08-31
修回日期: 2012-09-24
网络出版日期: 2012-10-09
基金资助
江苏省自然科学基金(No. BK2011390);江苏省高校优势学科(PAPD)资助项目.
Synthesis and Antiproliferatory Activity of Novel Diphyllin Hydroxamic Acid and Mercaptan Derivatives
Received date: 2012-08-31
Revised date: 2012-09-24
Online published: 2012-10-09
Supported by
Project supported by the Natural Science Foundation of Jiangsu Province (No. BK2011390) and the Priority Academic Program Development of Jiangsu Higher Education Instititutions (PAPD).
通过药效团整合策略将天然抗肿瘤活性木脂素山荷叶素与组蛋白去乙酰化酶抑制剂的药效团长链异羟肟酸或长链硫醇进行拼合, 得到了7个未见文献报道的山荷叶素衍生物, 通过核磁共振氢谱、碳谱、高分辨质谱等方法进行了结构表征. 并采用了噻唑蓝法(MTT)法对这些化合物的体外抑制肿瘤细胞增殖活性进行了测试, 异羟肟酸类衍生物具有较强的活性.
关键词： 山荷叶素; 组蛋白去乙酰化酶抑制剂; 抗肿瘤; 合成
赵育 , 倪春燕 , 张虞婷 , 朱俐 . 山荷叶素异羟肟酸和硫醇衍生物的合成与抑制肿瘤细胞增殖活性[J]. 有机化学, 2013 , 33(01) : 169 -173 . DOI: 10.6023/cjoc201208037
Seven novel diphyllin derivatives have been synthesized by incorporating histone deacetylase inhibitory functional groups into diphyllin. The structures were confirmed by 1H NMR, 13C NMR and HRMS. Their antiproliferative activity against three human cancer cell lines was investigated by methyl thiazolyl tetrazoliym (MTT) assay.
Key words： diphyllin; histone deacetylase inhibitors; antitumor; synthesis
[1] Bolden J. E.; Peart, M. J.; Johnstone, R. W. Nat. Rev. Drug Discovery 2006, 5, 769.
[2] Zhang, L.; Fang, H.; Xu, W. F. Med. Res. Rev. 2010, 30, 585.
[3] Qian, C. G.; Lai, C. J.; Bao, R.; Wang, D. G.; Wang, J.; Xu, G. X.; Atoyan, R.; Qu, H.; Yin, L.; Samson, M.; Zifcak, B.; Ma, A. W. S.; DellaRocca, S.; Borek, M.; Zhai, H. X.; Cai, X.; Voi M. Clin Cancer Res. 2010, 18, 4104.
[4] Witt, O.; Deubzer, H. E.; Milde, T.; Oehme, I. Cancer Lett. 2009, 277, 8.
[5] Cai, X.; Zhai, H. X.; Wang, J.; Forrester, J.; Qu, H.; Yin, L.; Lai, C. J.; Bao, R.; Qian, C. G. J. Med. Chem. 2010, 53, 2000.
[6] Chen, L. Q.; Petrelli, R.; Gao, G. Y.; Wilson, D. J.; Mclean, G. T.; Jayaram, H. N.; Sham, Y. Y.; Pankiewicz, K. W. Bioorg. Med. Chem. 2010, 18, 5950.
[7] Passarella, D.; Comi, D.; Vanossi, A.; Paganini, G.; Colombo, F.; Ferrante, L.; Zuco, V.; Danieli, B.; Zunino, F. Bioorg. Med. Chem. Lett. 2009, 19, 6358.
[8] Li, X. H.; Huang, D. W.; Sun, L.; Xiu, Z. L.; Nishino, N. Chin. J. Org. Chem. 2011, 31, 312 (in Chinese). (李晓晖, 黄大卫, 孙蕾, 修志龙, 西野宪和, 有机化学, 2011, 31, 312.)
[9] Zhao, Y.; Ni, C. Y.; Zhang, Y. T.; Zhu, L. Arch. Pharm. Chem. Life Sci. 2012, 8, 622.
[10] Zhao, Y.; Hui, J.; Wang, D.; Zhu, L. Chem. Pharm. Bull. 2010, 58, 1324.
[11] Guerrant, W.; Patil, V.; Canzoneri, J. C.; Oyelere A. K. J. Med. Chem. 2012, 55, 1465.
[12] Liu, X. H.; Song, H. Y.; Zhang, J. X.; Han, B. C.; Wei, X. N.; Ma, X. H.; Cui, W. K.; Chen, Y. Z. Mol. Inf. 2010, 29, 407.
[13] Zhao, Y.; Wang, D.; Hui, J.; Zhu, L. Med. Chem. Res. 2010, 19, 71.
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