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有机化学
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有机化学 ›› 2008, Vol. 28 ›› Issue (04): 700-704. 上一篇    下一篇

研究论文

非对称双(均三唑席夫碱)衍生物的合成及抗肿瘤活性

胡国强*, a， 侯莉莉a，谢松强a，杜钢军a，黄文龙b，张惠斌b   

  1. (a河南大学药物研究所 开封 475001)
    (b中国药科大学新药中心 南京 210009)
  • 收稿日期:2007-06-04 修回日期:2007-09-07 发布日期:2008-04-17
  • 通讯作者: 胡国强

Synthesis and Antitumor Activity of Asymmetric Bis(s-triazole Schiff-base)s

HU Guo-Qiang*,a,HOU Li-Lia,XIE Song-Qiangb,DU Gang-Juna
HUANG Wen-Longb,ZHANG Hui-Binb   

  1. (a Institute of Pharmacy, Henan University, Kaifeng 475001)
    (b Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009)
  • Received:2007-06-04 Revised:2007-09-07 Published:2008-04-17
  • Contact: HU Guo-Qiang

PDF

847

被引次数

88

为寻找新结构的水溶性抗癌先导化合物, 采用氨基均三唑硫代苯丙酮(1)与氨基均三唑硫醇(2a～2e)缩合得双均三唑单席夫碱化物3a～3e, 接着依次与氨基氯乙烷和水杨醛进行亲核取代和缩合反应, 分别得到含碱性侧链的单席夫碱4a～4e和非对称双席夫碱5a～5e. 所合成新化合物的结构经元素分析和光谱数据表征, 用甲基四噻唑蓝比色法(MTT)对新化合物进行了对于CHO, HL60和L1210 3种癌细胞株的体外活性试验. 在合成的15个新化合物中, 双席夫碱结构的抗癌活性最强, 其IC50值在20.0 μmol•L－1以下, 尤其是均三唑环连有双供电子取代基时(如化合物5c), 表现出潜在的活性, 其抗癌活性与上市药物比生群相当, 具有侯选药物研究的价值.

关键词: 均三唑, 双席夫碱, 合成, 抗肿瘤活性

To discover novel structurally soluble lead compounds for antitumor researches, 1-amino-2-(p-methoxyphenyl)-5-(2-benzoylethylthio)-s-triazole (1) was condensed with 1-amino-s-triazole-5-thiols (2a～2e) in the presence of concentrated H2SO4 to obtain bis-(s-triazole) Schiff-bases 3a～3e, which were subjected to a nucleophilic substitution with N,N-dimethyl-2-chloroethylamine to produce the corresponding bis-(s-triazole) Schiff-bases bearing a basic side chain 4a～4e. Condensation of compounds 4a～4e with salicylaldehyde afforded asymmetric bis-(s-triazole Schiff-base)s 5a～5e, namely 2-(p-methoxyphenyl)-1-salicylideneamino-5-{3-phenyl-3-[N-(2-(2-dimethylaminoethylthio)-s-triazol-1-yl)imino]propylthio}-s-tria-zoles, respectively. The structures of new com-pounds synthesized were characterized by elemental analysis and spectral data, and their in vitro an-titumor activity was also assayed against three cancer cells of CHO, HL60 and L1210 by an methylthiazole-trazolium (MTT) method. Among the fifteen novel compounds synthesized, bis(Schiff base)s 5a～5e showed the most potent cytotoxicity with the IC50 below 20.0 μmol•L－1, especially 5c bearing two (2-methoxyphenyl triazole) rings was comparable to bisantrene.

Key words: bis-(Schiff-base), s-triazole, synthesis, antitumor activity