含多(硫/氧)醚侧链吡啶均三唑席夫碱的合成与抗癌活性  

Synthesis and Antitumor Activity of Pyridyl S-Triazole Schiff-Bases Containing Functional Side-Chain of Poly(thio-oxo)ether

作　　者：胡国强[1] 王海燕[1] 毋小魁[1] 王新[1] 张智强[1] 谢松强[1] 黄文龙[2] 

机构地区：[1]河南大学药物研究所,河南开封475004 [2]中国药科大学,南京210009

出　　处：《中国药学杂志》2009年第19期1511-1514,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(20872028)

摘　　要：目的研究含功能基侧链多(硫/氧)醚吡啶均三唑席夫碱衍生物的合成方法及抗癌活性。方法吡啶噻二唑硫醇(1)与甲氧乙氧氯甲烷进行亲核取代反应得多(硫/氧)醚吡啶噻二唑(2),与水合肼通过开-闭环加成-消除反应得中间体化合物多(硫/氧)醚吡啶均三唑(3),再与各种芳香醛缩合得相应席夫碱目标化合物。采用MTT法研究了目标化合物体外抑制L1210和B16癌细胞的活性。结果合成了12个新化合物,其结构经元素分析、IR、1H-NMR、MS确证。天然芳香醛席夫碱化合物4a,4b,4c,4d,4e表现明显的体外抗癌活性。结论天然芳香醛缩多(硫/氧)醚吡啶均三唑席夫碱衍生物有可能成为新型结构的抗癌先导化合物。OBJECTIVE To study the synthesis and antitumor activity ofpyridyl S-triazole Schiff-bases containing functional side-chain of poly（thio-oxo）ether. METHODS The nucleophilie substitution of starting material, pyridinylthiadiazolethiol（1）, with 2-methoxyethoxy ehloromethane gave poyl（thio-oxo）ether pyridyl thiadiazole（2） followed by addition-elimination reaction via opening-closure mechanism of thiadiazole ring to the intermediate poyl（thio-oxo）ether pyridyl S-triazole （3）; then the title Shift-base compounds （4） were synthesized by condensation of compounds 3 with various aromatic aldehydes, The in vitro antitumor activity of novel synthesized compounds to L1210 and B16 cells was evaluated by MTT method. RESULTS Twelve novel compounds were synthesized, and their structures were characterized by IR, XH-NMR, MS spectra and element analysis. Among them, naturally aromatic aldehyde Schiff-bases 4a, 4c, 4d and 4e showed potential antitumor activity. CONCLUSION Naturally aromatic aldehyde pyridyl triazole Schiff-bases showed a certain antitumor activity, and were worth further developing as promising lead compounds.

关 键 词：均三唑 硫/氧醚 吡啶 席夫碱 合成 抗癌活性 

分 类 号：R914[医药卫生—药物化学]