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2020 , Vol. 40 >Issue 2: 478 - 488

DOI: https://doi.org/10.6023/cjoc201907043

研究论文

基于咔唑的新型碳酰腙衍生物的合成及蛋白酪氨酸磷酸酶1B(PTP1B)抑制活性评价

  • 李英俊 ,
  • 刘雪洁 ,
  • 刘季红 ,
  • 高立信 ,
  • 靳焜 ,
  • 盛丽 ,
  • 杨鸿境 ,
  • 林乐弟 ,
  • 李佳
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  • a 辽宁师范大学化学化工学院 大连 116029;
    b 大连理工大学化学分析测试中心 大连 116023;
    c 中国科学院上海药物研究所 国家新药筛选中心 药物研究国家重点实验室 上海 201203;
    d 大连理工大学精细化工国家重点实验室 大连 116012

收稿日期: 2019-07-27

  修回日期: 2019-09-09

  网络出版日期: 2019-10-09

基金资助

辽宁省自然科学基金（No.20102126）资助项目.

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Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Carbazole-Based Carbohydrazone Derivatives

  • Li Yingjun ,
  • Liu Xuejie ,
  • Liu Jihong ,
  • Gao Lixin ,
  • Jin Kun ,
  • Sheng Li ,
  • Yang Hongjing ,
  • Lin Ledi ,
  • Li Jia
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  • a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029;
    b Chemistry Analysis and Inspection Center, Dalian University of Technology, Dalian 116023;
    c National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203;
    d State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012

Received date: 2019-07-27

  Revised date: 2019-09-09

  Online published: 2019-10-09

Supported by

Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126).

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摘要

合成出了一系列新型基于咔唑的单-/双-碳酰腙衍生物3和4.利用1H NMR、13C NMR、IR和元素分析对其进行了结构表征.评价了目标化合物对蛋白酪氨酸磷酸酶1B（PTP1B）的抑制活性，讨论了结构与活性的关系.实验结果显示，大部分化合物对PTP1B具有良好的抑制活性，其中1，5-双[（9-丁基-3-咔唑基）亚甲基]碳酰腙（4c）的抑制活性最高，IC50=（4.81±0.41）μmol/L，且活性高于对照药物齐墩果酸.对目标化合物1-[（9-庚基-3-咔唑基）亚甲基]碳酰腙（3f）和4c进行分子对接研究和密度泛函理论（DFT）计算.分子对接结果表明，化合物3f和4c结合到PTP1B酶由螺旋α3和α6形成的活性位点，与PTP1B酶通过氢键、极性、疏水和π-π等相互作用形成了稳定的复合物.

关键词： 碳酰腙; 咔唑; 合成; PTP1B抑制剂; 分子对接; DFT计算

本文引用格式

李英俊 , 刘雪洁 , 刘季红 , 高立信 , 靳焜 , 盛丽 , 杨鸿境 , 林乐弟 , 李佳 . 基于咔唑的新型碳酰腙衍生物的合成及蛋白酪氨酸磷酸酶1B(PTP1B)抑制活性评价[J]. 有机化学, 2020 , 40(2) : 478 -488 . DOI: 10.6023/cjoc201907043

Abstract

A series of novel carbazole-based mono-/bis-carbohydrazone derivatives 3 and 4 were synthesized. Their structures were characterized by 1H NMR, 13C NMR, IR spectra and elemental analysis. The inhibitory activities of all synthesized compounds against protein tyrosine phosphatase 1B (PTP1B) were evaluated, and the structure-activity relationship was discussed. The results indicated that most of the compounds had good inhibitory activity against PTP1B, and 1,5-bis[(9-butyl-3-carba-zolyl)methylene]carbohydrazone (4c) showed the highest inhibitory activity against PTP1B with IC50=(4.81±0.41) μmol/L and the activity was higher than that of the control drug oleanolic acid. Molecular docking and density functional theory (DFT) calculations of 3f and 4c were carried out. The results of molecular docking indicated that 1-[(9-heptyl-3-carbazolyl)meth-ylene]carbohydrazone (3f) and 4c bind to an active site of PTP1B enzyme formed by the helices α3 and α6, and formed a stable complex respectively with PTP1B enzyme by hydrogen bonds, polar, hydrophobic and π-π interactions.

Key words： carbohydrazone; carbazole; synthesis; PTP1B inhibitor; molecular docking; DFT calculations

参考文献

[1] Sun, R.; Deng, X. X.; Zhang, D. D.; Xie, F. Z.; Wang, D.; Wang, J. T.; Tavallaie, M. S.; Jiang, F. Q.; Fu, L. Bioorg. Chem. 2019, 87, 12.
[2] Paudel, P.; Seong, S. H.; Park, H. J.; Jung, H. A.; Choi, J. S. Mar. Drugs 2019, 17, 166.
[3] Lima, R. C. L.; Kato, L.; Kongstad, K. T.; Staerk, D. J. Funct. Foods 2018, 45, 444.
[4] Xu, H. M.; Mu, C.; Bao, D.; Xing, Q. L. Chin. J. Diabetes Mellitus 2018, 10, 735
[5] Ferhati, X.; Matassini, C.; Fabbrini, M. G.; Goti, A.; Morrone, A.; Cardona, F.; Moreno-Vargas, A. J.; Paoli, P. Bioorg. Chem. 2019, 87, 534.
[6] Liu, H. Y.; Sun, D. W.; Du, H.; Zheng, C. J.; Li, J. Y.; Piao, H. R.; Li, J.; Sun, L. P. Eur. J. Med. Chem. 2019, 172, 163.
[7] Sun, L. P.; Wang, P. P.; Xu, L. L.; Gao, L. X.; Li, J.; Piao, H. R. Bioorg. Med. Chem. Lett. 2019, 29, 1187.
[8] Kostrzewa, T.; Styszko, J.; Gorska-Ponikowska, M.; Sledzinski, T.; Kuban-Jankowska, A. Anticancer Res. 2019, 39, 3379.
[9] Kostrzewa, T.; Przychodzen, P.; Gorska-Ponikowska, M.; Kuban-Jankowska, A. Anticancer Res. 2019, 39, 745.
[10] Li, X. Q.; Xu, Q.; Li, C.; Luo, J.; Li, X. X.; Wang, L. J.; Jiang, B.; Shi, D. Y. Eur. J. Med. Chem. 2019, 166, 178.
[11] El-Sherif, A. A.; Elbastweesy, E. R.; El-Reash, G. M. A.; Aljahdali, M. S. Int. J. Electrochem. Sci. 2019, 14, 7241.
[12] Choudhary, S.; Varshney, S.; Varshney, A. K. J. Appl. Chem. Res. 2016, 10, 99.
[13] Božić, A.; Marinković, A.; Bjelogrlić, S.; Todorović, T. R.; Cvijetić, I. N.; Novaković, I.; Muller, C. D.; Filipović, N. R. RSC Adv. 2016, 6, 104763.
[14] Fetoh, A.; El-Gammal, O. A.; El-Reash, G. M. A. J. Mol. Struct. 2018, 1173, 100.
[15] Ibrahim, S. A.; Elsaman, T. J. Pharm. Res. Int. 2018, 21, 1.
[16] Muğlu, H.; Çavuş, M. S.; Bakır, T.; Yakan, H. J. Mol. Struct. 2019, 1196, 819.
[17] Božić, A. R.; Filipović, N. R.; Novaković, I. T.; Bjelogrlić, S. K.; Nikolić, J. B.; Drmanić, S. Ž.; Marinković, A. D. J. Serb. Chem. Soc. 2017, 82, 495.
[18] Fetoh, A.; Salah, Z.; El-Reash, G. M. A. Appl. Organometal. Chem. 2019, 33, e4727.
[19] Rubčić, M.; Pisk, J.; Pičuljan, K.; Damjanović, V.; Lovrić, J.; Vrdoljak, V. J. Mol. Struct. 2019, 1178, 222.
[20] Chohan, Z. H.; Pervez, H.; Khan, K. M.; Supuran, C. T. J. Enzyme Inhib. Med. Chem. 2005, 20, 81.
[21] Iqbal, S.; Saleem, M.; Azim, M. K.; Taha, M.; Salar, U.; Khan, K. M.; Perveen, S.; Choudhary, M. I. Bioorg. Chem. 2017, 72, 89.
[22] Zhang, L.; Ge, Y.; Song, H. M.; Wang, Q. M.; Zhou, C. H. Bioorg. Chem. 2018, 80, 195.
[23] Tang, Y. B.; Liu, J. Z.; Zhang, S. E.; Du, X.; Nie, F. L.; Tian, J. Y.; Ye, F.; Huang, K.; Hu, J. P.; Li, Y.; Xiao, Z. Y. Chem. Med. Chem. 2014, 9, 918.
[24] Li, Y.-J.; Wang, S.-Y.; Jin, K.; Gao, L.-X.; Sheng, L.; Zhang, N.; Yang, K.-D.; Zhao, Y.; Li, J. Chin. J. Org. Chem. 2018, 38, 1242(in Chinese). (李英俊, 王思远, 靳焜, 高立信, 盛丽, 张楠, 杨凯栋, 赵月, 李佳, 有机化学, 2018, 38, 1242.)
[25] Li, Y.-J.; Wang, S.-Y.; Jin, K.; Gao, L.-X.; Sheng, L.; Zhang, N.; Liu, J.-H.; Li, J. Chin. J. Org. Chem. 2018, 39, 491(in Chinese). (李英俊, 王思远, 靳焜, 高立信, 盛丽, 张楠, 刘继红, 李佳, 有机化学, 2018, 39, 491.)
[26] Li, Y.-J.; Zhao, Y.; Jin, K.; Gao, L.-X.; Sheng, L.; Liu, X.-J.; Yang, H.-J.; Lin, L.-D.; Li, J. Chin. J. Org. Chem. 2019, 39, 2599(in Chinese). (李英俊, 赵月, 靳焜, 高立信, 盛丽, 刘雪洁, 杨鸿境, 林乐弟, 李佳, 有机化学, 2019, 39, 2599.)
[27] Bondock, S.; Alqahtani, S.; Fouda, A. M. Synth. Commun. 2019, 49, 2188.
[28] Krishnan, K. G.; Ashothai, P.; Padmavathy, K.; Lim, W. M.; Mai, C. W.; Thanikachalam, P. V.; Ramalingan, C. New J. Chem. 2019, 43, 12069.
[29] Li, G.; Tang, H. D.; Liu, C. F.; Liao, X. Y.; Li, S. C.; Shu, Z. N.; Yu, H.; Peng, Y. Bioorg. Chem. 2019, 90, UNSP 103074.
[30] Adib, M.; Peytam, F.; Shourgeshty, R.; Mohammadi-Khanaposhtani, M.; Jahani, M.; Imanparast, S.; Faramarzi, M. A.; Larijani, B.; Moghadamnia, A. A.; Esfahani, E. N.; Bandarian, F.; Mahdavi, M. Bioorg. Med. Chem. Lett. 2019, 29, 713.
[31] Caruso, A.; Ceramella, J.; Iacopetta, D.; Saturnino, C.; Mauro, M. V.; Bruno, R.; Aquaro, S.; Sinicropi, M. S. Molecules 2019, 24, 1912.
[32] Shaikh, M. S.; Kanhed, A. M.; Chandrasekaran, B.; Palkar, M. B.; Agrawal, N.; Lherbet, C.; Hampannavar, G. A.; Karpoormath, R. Bioorg. Med. Chem. Lett. 2019, 29, 2338.
[33] Tamene, D.; Endale, M. Adv. Pharm. Sci. 2019, 2019, 1.
[34] Zhou, S. L.; Tang, H. L.; Yao, M.; Cao, S. N.; Zhuang, L. Y.; Cao, C. S. Chem. Pap. 2019, 73, 2477.
[35] Rifati-Nixha, A.; Arslan, M.; Gençer, N.; Çıkrıkıçı, K.; Gökçe, B.; Arslan, O. J. Biochem. Mol. Toxicol. 2019, 33, e22306.
[36] Eseyin, O. A.; Edem, E.; Johnson, E.; Ahmad, A.; Afzal, S. Trop. J. Pharm. Res. 2018, 17, 537.
[37] Dragancea, D.; Shova, S.; Enyedy, É. A.; Breza, M.; Rapta, P.; Carrella, L. M.; Rentschler, E.; Dobrov, A.; Arion, V. B. Polyhedron 2014, 80, 180.
[38] El-Reash, G. M. A.; El-Gammal, O. A.; Radwan, A. H. Spectro-chim. Acta A 2014, 121, 259.
[39] Jagadeeswari, S.; Paramaguru, G.; Thennarasu, S.; Renganathan, R. J. Mol. Struct. 2014, 1060, 191.
[40] Budreckiene, R.; Buika, G.; Grazulevicius, J. V.; Jankauskas, V.; Staniskiene, B. J. Photochem. Photobiol. A 2006, 181, 257.
[41] 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.
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