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

doi:10.6023/cjoc201412014

Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (8): 1665-1672.DOI: 10.6023/cjoc201412014 Previous Articles Next Articles

ARTICLE

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

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 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

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 Published:2015-04-30
Supported by:
Project supported by the Science and Technology Research Program of Liaoning Provincial Department of Education (No. 2009A426).

1. Synthesis and Properties of Novel Tripod Type Multi-benzimidazole Quaternary Ammonium Compounds.PDF(1424KB)

Abstract

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

Cite this article

Zhang Chenglu, Guo Yang, Chen Ying, Sun Lijie, Cheng Anqi, Zhao Na, Zhao Baocheng, Tang Jie, Xi Huan. Synthesis and Properties of Novel Tripod Type Multi-benzimidazole Quaternary Ammonium Compounds[J]. Chin. J. Org. Chem., 2015, 35(8): 1665-1672.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Song, L.; Xie, Y. Y.; Wang, H. Z. Chin. J. Med. Chem. 2000, 92. (in Chinese). (宋琳, 谢毓元, 王惠贞, 中国药物化学杂志, 2000, 92.)
[2] Meng, J. P.; Lu, Y. H.; Halqam, I.; Zhou, C. H. Chin. J. Biochem. Pharmacol. 2008, 29, 418. (in Chinese). (孟江平, 卢一卉, 海力且木·依不那音, 周成合, 中国生化药物杂志, 2008, 29, 418.)
[3] Guo. Y. C.; Zhou, L. H.; Qiao. Z. P. Chin. J. Inorg. Chem. 2006, 134 (in Chinese). (郭应臣, 卓立宏, 乔占平, 无机化学学报, 2006, 134.)
[4] Ören, I.; Temiz, Ö.; Yalc?n, I.; ?ener, E.; Altanlar, N. Eur. Pharm. Sci. 1989, 7, 153.
[5] Klimešová, V.; Ko??á, J.; Pour, M.; Stachel, J.; Waisser, K.; Kaustová, J. Eur. Med. Chem. 2002, 33, 137.
[6] Ansari, K. F.; Lal, C. Eur. J. Med. Chem. 2009, 44, 2294.
[7] Rajakumara, P.; Sekara, K.; Shanmugaiahb, V.;, Mathivananb, N. Bioorg. Med. Chem. Lett. 2008, 18, 4416.
[8] Beaulieu, P. L.; Bousquet, Y.; Gauthier, J.; Gillard, J.; Marquis, M.; McKercher, G.; Pellerin, C.; Valois, S.; Kukolj, G. J. Med. Chem. 2004, 47, 6884.
[9] Hirashima, S.; Suzuki, T.; Ishida, T.; Noji, S.; Yata, S.; Ando, I.; Komatsu, M.; Ikeda, S.; Hashimoto, H. T. J. Med. Chem. 2006, 49, 4721.
[10] Asthana, S.; Shukla, S.; Vargiu, A. V. Biochemistry 2013, 52, 3752.
[11] Li, Y. F.; Wang, G. F.; He, P. L.; Huang, W. G.; Zhu, F. H. ; Gao, H. Y.; Tang, W.; Luo, Y.; Feng, C. L.; Shi, Li. P.; Ren, Y. D.; Lu, W.; Zuo, J. P. J. Med. Chem. 2006, 49, 4790.
[12] Fang, X. P.; Mei, X. G. Foreign Med. Sci. 2005, 32, 115 (in Chinese). (方学平, 梅兴国, 国外医学, 2005, 32, 15.)
[13] Combs, A. P.; Zhu, W. Y.; Crawley, M. L.; Glass, B.; Polam, P.; Sparks, R. B.; Modi, D.; Takvorian, A.; McLaughlin, E.; Yue, E. W.; Wasserman, Z.; Bower, M.; Wei, M.; Rupar, M.; Ala, P. J.; Reid, B. M.; Ellis, D.; Gonneville, L.; Emm, T.; Taylor, N.; Yeleswaram, S.; Li Y. L.; Richard, W.; Timothy, C. B.; Gregory, H.; Phillip, C. C.; Liu, B. M. J. Med. Chem. 2006, 49, 3774.
[14] Ong, J. X.; Yap, C. W.; Ang, W. H. Inorg. Chem. 2012, 51, 12483.
[15] Erion, M. D.; Dang, Q.; Reddy, M. R.; Kasibhatla, S. R.; Huang, J. W.; Lipscomb, W. N.; Poelje, P. D. J. Am. Chem. Soc. 2008, 129, 15480.
[16] Dang, Q.; Kasibhatla, S. R.; Xiao, W.; Liu, Y.; DaRe, J.; Taplin, F.; Reddy, K. R.; Scarlato, G. R.; Gibson, T.; Poelje, P. D.; Potter, S. C.; Erion, M. D. J. Med. Chem. 2010, 53, 441.
[17] Settimo, F. D.; Primofiore, G.; Settimo, A. D. J. Med. Chem. 2001, 44, 4359.
[18] Ramla, M. M.; Omar, M. A.; El-Khamry, A-M. M.; El-Diwani, H. I. Bioorg. Med. Chem. 2006, 14, 7324.
[19] Rewcastle, G. W.; Gamage, S. A.; Flanagan, J. U. J. Med. Chem. 2011, 54, 105.
[20] Lavecchia, A.; Giovanni, C. D.; Pesapane, A.; Montuori, N.; Ragno, P.; Martucci, N. M.; Masullo, M.; Vendittis, E. D.; Novellino, E. J. Med. Chem. 2012, 55, 4142.
[21] Zhang, C. L.; Wang, X.; Guo, Y.; Wu, Y. F.; Gao, L. N.; Sun, L. J. Chai, J. H.; Zhu, C. A. Chin. J. Org. Chem. 2014, 34, 2331 (in Chinese). (张成路, 王雪, 国阳, 吴一非, 高丽娜, 孙丽杰, 柴金华, 朱长安, 有机化学, 2014, 34, 2331.)
[22] Vladislav, Y. K.; Igor, B. K. ; Vyacheslav, Y. S. Heteroat. Chem. 2005, 16, 492.
[23] Zhang, C. L.; Sun, L. J.; Wu, F. Y.; Qu, R. F.; Zhu, C. A.; Wang, X.; Chai, J. H.; Guo, Y.; Hu, X. Chem. J. Chin. Univ. 2014, 35, 1445 (in Chinese). (张成路, 孙立杰, 武飞宇, 曲瑞峰, 朱长安, 王雪, 柴金华, 国阳, 胡雪, 高等学校化学学报, 2014, 35, 1445.)
[24] Fukuyama, Y.; Tanimura, R.; Maeda, K. Anal. Chem. 2012, 84, 4237.
[25] Singh, N.; Jang, D. O. Org. Lett. 2007, 9, 1991.
[26] Martinez, M.; Scancenon, F. Chem. Rev 2003, 103, 4419.
[27] Kim, Y. H.; Sun, G. Text. Res. J. 2001, 71, 318.
[28] Kar, C.; Basu, A.; Das, G. Tetrahedron 2012, 53, 4754.
[29] Zhang, Y. N.; Zhang, W.; Hong, D.; Shi, L.; Shen, Q.; Li, J. Y.; Li, J.; Hua, L. H. Bioorg. Med. Chem. 2008, 16, 8697.
[30] Huang, W. G.; Jiang, Y. Y.; Li, Q.; Li, J.; Li, J. Y.; Lu, W.; Cai, J. C. Tetrahedron 2005, 61, 1863.
[31] Sun, L. P.; Shen, Q.; Piao, H. H.; Ma, W. P.; Gao, L. X.; Zhang, W.; Nan, F. J.; Li, J.; Piao, H. R. Eur. J. Med. Chem. 2011, 46, 3630.
[32] Alam, M. M.; Nazreen, S.; Haider, S.; Shafi, S.; Yar, M. S.; Hamid, H.; Alam, M. S. Pharm. Chem. Life Sci. 2011, 45, 11
[33] Khatri, V. K.; Chahar, M.; Pavani, K.; Pandey, P. S. J. Org. Chem. 2007, 72, 10224.
[34] Boye, B.; Keramanea, E. M.; Monterob, J. L.; Roquea, J. P. Synth. Commun. 1998, 28, 1737.
[35] Wang, Z. T.; Zhu, L.; Yin, F.; Su, Z. Q.; Li, Z. D.; Li, C. Z. J. Am. Chem. Soc. 2012, 134, 4258.
[36] Matsuo, J.; Iida, D.; Yamanakaa, H.; Mukaiyamaa, T. Tetrahedron 2003, 59, 6739.
[37] Sun, J.; Feng, X. J.; Zhao, Z. R.; Yamamoto, Y.; Bao, M. Tetrahedron 2014, 70, 7166.
[38] Niknam, K.; Kiasat, A. R.; Kazemi, F.; Hossienia, A. Phosphorus, Sulfur, Silicon Relat. Elem.2003, 178, 1385.
[39] Li, Z.; Sheng, C.; Qiu, H.; Zhang, Y. The New J. Org. Synth. 2009, 39, 412.
[40] Zhang, J.; Cui, H. L.; Hojo, M.; Shuang, S. M.; Dong, C. Bioorg. Med. Chem. Lett. 2012, 22, 343.
[41] Caliendoa, G.; Fiorinoa, F.; Perissuttia, E.; Severinoa, B.; Gessib, S.; Cattabrigab, E.; Boreab, P. A.; Santagadaa, V. Eur. J. Med. Chem. 2001, 36, 873.
[42] Boger, D. L.; Palanki, M. S. S. J. Am. Chem. Soc. 1992, 114, 9318.
[43] Tan, H. H.; Ong, W. M.; Lai, S. H. Singapore Med. J. 2007, 48, 582.

新型三脚架型多苯并咪唑季铵盐类化合物的合成及性能

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

PDF

Supporting Info.

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Mengjia Xiao, Xike Gao. Design, Synthesis and Anti-inflammatory Activity of Azulene Derivatives Containing Benzimidazole Unit [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3246-3256.
[2]	Tianyang Wang, Yan-Mei Li. Progress on the Synthesis and Activity of Cyclic Dinucleotides as Stimulator of Interferon Gene (STING) Agonists [J]. Chinese Journal of Organic Chemistry, 2023, 43(3): 892-913.
[3]	Binghan Lin, Jibin Zhuo, Caixia Lin, Yong Gao, Yaofeng Yuan. Synthesis and Nucleotide Recognition Properties of Carborane-Based Benzoimidazolium Cyclophane [J]. Chinese Journal of Organic Chemistry, 2022, 42(8): 2551-2558.
[4]	Jing Zhao, Zhe Jin, Run Wang, Xin'geng Zhang, Yingmei Han, Chun Hu, Xiaoping Liu, Chuanming Zhang, Liping Jin. Design, Synthesis and Anticancer Activity of 2-((Pyridin- 2-ylmethyl)thio)-1H-benzimidazole Derivatives [J]. Chinese Journal of Organic Chemistry, 2022, 42(7): 2172-2183.
[5]	Siyu Zhu, Xinyu Huo, Qin Ma, Wei Chen, Jie Zhang, Liang Guo. Design, Synthesis, and Antitumor Activity of β-Carboline-Benzimidazole Hybrids [J]. Chinese Journal of Organic Chemistry, 2022, 42(4): 1129-1135.
[6]	Zirong Zeng, Mengmeng Zhang, Hong Wang, Jia Li, Yuewei Guo, Mingzhi Su. Chemical Constituents of Sinularia nanolobata from the South China Sea [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 891-895.
[7]	Xiaojing Tian, Zhenzhen Fan, Si Jiang, Zhiwei Li, Jiangsheng Li, Yuefei Zhang, Cuihong Lu, Weidong Liu. Metal-Free Synthesis of Benzimidazo[1,2-c]quinazolines from N-Cyanobenzimidazoles via Double C—H Functionalizations [J]. Chinese Journal of Organic Chemistry, 2022, 42(11): 3684-3692.
[8]	Yuyu Guo, Xiangjie Chen, Shiwu Li, Zhihua Cai, Lin He. Synthesis of Mutisubstituted Dihydropyridino[1,2-a]benzimidazole Derivatives via Tandem Reaction of 2-Arylbenzimidazoles [J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3692-3700.
[9]	Fengxing Li, Xin Lu, Xu Liu, Lulu Su, Xiaoliu Li, Hua Chen. Structural Modification of Benzimidazole-Iminosugars and Their Inhibitory Activities against β-Glycosidases [J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3643-3651.
[10]	Yingjun Li, Ledi Lin, Jihong Liu, Lixin Gao, Li Sheng, Kun Jin, Xuejie Liu, Hongjing Yang, Jia Li. Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel N-Acylhydrazone Derivatives Containing Carbazole and Aromatic Ring/Aromatic Fused Heterocycle [J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3593-3607.
[11]	Yingjun Li, Ledi Lin, Kun Jin, Lixin Gao, Li Sheng, Jihong Liu, Jia Li. Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Arylaminoacetylhydrazone Derivatives Containing Carbazole Moiety [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3157-3170.
[12]	Xu Liu, Lulu Su, Zhaoxi Zhou, Liping Niu, Ligang Gao, Huanhuan Ju, Fengxing Li, Xiaoliu Li, Hua Chen. Design and Synthesis of Benzimidazole-Iminosugars and Their Inhibitory Activities against Glycosidases [J]. Chinese Journal of Organic Chemistry, 2021, 41(7): 2861-2874.
[13]	Lin Mei, Wu Fan, Liu Tianhui, Chen Zhitao, Xu Xiuzhi, Ke Fang. Visible-Light Promoted Preparation of Benzimidazoles by Eosin Y Catalyzed Reaction of Benzonitrile Derivatives in Water [J]. Chinese Journal of Organic Chemistry, 2020, 40(8): 2563-2569.
[14]	Wang Xin, Li Guofeng, Sun Kai, Zhang Bing. Peroxide-Induced Radical Relay Carbocyclization towards Polycyclic Benzimidazole[2,1-a]isoquinolines [J]. Chinese Journal of Organic Chemistry, 2020, 40(4): 913-921.
[15]	Zhang Chenglu, Wang Huayu, Yu Xiangkun, Yang Jingyi, Li Chuanyin, Gong Rongqin, Song Fulu, Sun Yuedong. Synthesis of Amide Thioether Bridged 1,3-Selenazole and 1,2,4-Triazole Derivatives and Their Inhibitory Activity against Cell Division Cycle Phosphatase B (Cdc25B) [J]. Chinese Journal of Organic Chemistry, 2020, 40(2): 432-439.