有机化学 ›› 2015, Vol. 35 ›› Issue (8): 1665-1672.DOI: 10.6023/cjoc201412014 上一篇    下一篇

研究论文

新型三脚架型多苯并咪唑季铵盐类化合物的合成及性能

张成路, 国阳, 陈莹, 孙丽杰, 程安琪, 赵娜, 赵宝成, 唐杰, 袭焕   

  1. 辽宁师范大学化学化工学院 辽宁省生物与制药重点实验室 大连 116029
  • 收稿日期:2014-12-08 修回日期:2015-03-25 出版日期:2015-08-25 发布日期:2015-04-30
  • 通讯作者: 张成路 E-mail:zhangchenglu@lnnu.edu.cn
  • 基金资助:

    辽宁省教育厅科学技术研究(No. 2009A426)资助项目.

Synthesis and Properties of Novel Tripod Type Multi-benzimidazole Quaternary Ammonium Compounds

Zhang Chenglu, Guo Yang, Chen Ying, Sun Lijie, Cheng Anqi, Zhao Na, Zhao Baocheng, Tang Jie, Xi Huan   

  1. Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029
  • Received:2014-12-08 Revised:2015-03-25 Online:2015-08-25 Published:2015-04-30
  • Supported by:

    Project supported by the Science and Technology Research Program of Liaoning Provincial Department of Education (No. 2009A426).

合成了14个具有复合功能的三脚架型多苯并咪唑季铵盐类化合物3a~3n, 并对其进行了结构表征. 探究了目标化合物 3 对 Cdc25B和PTP1B的抑制活性, 结果发现, 目标产物3d3e3i3j3l对Cdc25B 表现出优良的抑制活性, 其中3d3e3j3l的IC50值低于参照物钒酸钠, 有望成为用于治疗癌症的潜在的Cdc25B 抑制剂; 3d3e3i3l对PTP1B 表现出良好的抑制活性, 3l的IC50值低于参照物齐墩果酸, 有望作为用于治糖尿病潜在的 PTP1B 抑制剂. 研究了生命体系中重要的6种不同阴离子对4个代表性目标化合物的荧光猝灭, 结果发现, I-对目标化合物表现出了优良的猝灭效果, 其中对3c3e猝灭作用最为明显, 有望成为一种潜在的I-荧光识别探针.

关键词: 苯并咪唑, 药物活性, 荧光探针, Cdc25B, PTP1B

Fourteen novel tripod type multi-benzimidazole quaternary ammoniums (3a~3n) with complex functions were synthesized for the first time and the structures of the target molecules were well characterized. The inhibitory activities of Cdc25B and PTP1B of 3 were explored. The results showed that 3d, 3e, 3i, 3j and 3l exhibit excellent inhibitory activity against Cdc25B, wherein the IC50 values of 3d, 3e, 3j and 3l were lower than the reference Na3VO4, which were expected to be potential Cdc25B inhibitors for the treatment of cancer. Compounds 3d, 3e, 3i and 3l showed good inhibitory activity against PTP1B, wherein the IC50 value of 3l was lower than the reference oleanolic acid, which may be used as a potential PTP1B inhibitor for the treatment of diabetes. Meanwhile, the fluorescence quenching of six kinds of anions on four target compounds was also studied. It was found that I-exhibited excellent quenching effect, 3c and 3e behaved the best quenching effect and may be a potential recognition fluorescent I-sensor probe.

Key words: benzimidazole, drug activity, fluorescent sensor probe, CDc25B, PTP1B