Citation: Li Yingjun, Wang Siyuan, Jin Kun, Gao Lixin, Sheng Li, Zhang Nan, Liu Jihong, Li Jia. Synthesis and Cdc25B/PTP1B Inhibitory Activity Evaluation of Novel Acylhydrazone Derivatives Containing Carbazole Moity[J]. Chinese Journal of Organic Chemistry, ;2019, 39(2): 491-499. doi: 10.6023/cjoc201806042 shu

Synthesis and Cdc25B/PTP1B Inhibitory Activity Evaluation of Novel Acylhydrazone Derivatives Containing Carbazole Moity

Li Yingjun ^a ,
Wang Siyuan ^a ,
Jin Kun ^b ,
Gao Lixin ^c ,
Sheng Li ^c ,
Zhang Nan ^a ,
Liu Jihong ^d ,
Li Jia ^c,,

a.
College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029
b.
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012
c.
State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
d.
Chemistry Analysis & Research Center, Faculty of Chemical, Environmental & Biological Science and Technology, Dalian University of Technology, Dalian 116023

Corresponding author: Li Jia, chemlab.lnnu@163.com
Received Date: 27 June 2018
Revised Date: 22 August 2018
Available Online: 10 February 2018
Fund Project: Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126)the Natural Science Foundation of Liaoning Province 20102126

Figures(5)

A series of novel acylhydrazone derivatives 6 containing carbazole moity were synthesized by carbazole and 4-cyanobenzyl chloride as starting materials via multi-step reactions. Their structures were characterized by IR, ¹H NMR, ¹³C NMR spectra and elemental analysis. All synthesized target compounds were evaluated for the inhibitory activities against Cdc25B and PTP1B. The results show that the target compounds display significant inhibitory activities against Cdc25B/PTP1B. Among them, compound 4-((carbazol-9-yl)methyl)-N'-(2-hydroxy-1-naphthalenylmethylene)benzoyl hydrazide (6g) had the highest inhibitory activities against Cdc25B and PTP1B with IC₅₀ values of (2.16±0.38) and (1.06±0.23) μg/mL, respectively. The molecular docking results indicated that the hydrogen bond and hydrophobic interaction formed between compound 6g and Cdc25B/PTP1B enzyme.
- acylhydrazone,
- carbazole,
- synthesis,
- Cdc25B and PTP1B inhibitor,
- molecular docking
1. [1]
  Ommis, V.; Demurtas, M.; Deplano, A.; Balboni, G.; Baldisserotto, A.; Manfredini, S.; Pacifico, S.; Liekens, S.; Balzarini, J. Molecules 2016, 21, 579. doi: 10.3390/molecules21050579
2. [2]
  Temirak, A.; Shaker, Y. M.; Ragab, F. A. F.; Ali, M. M.; Soliman, S. M.; Mortier, J.; Wolber, G.; Ali, H. I.; Diwani, H. I. E. Arch. Pharm. Chem. Life Sci. 2014, 347, 291. doi: 10.1002/ardp.v347.4
3. [3]
  Wu, D. Y.; Jin, F. F.; Lu, W. Q.; Zhu, J.; Li, C.; Wang, W.; Tang, Y.; Jiang, H. L.; Huang, J.; Liu, G. X.; Li, J. Chem. Biol. Drug Des. 2012, 79, 897. doi: 10.1111/jpp.2012.79.issue-6
4. [4]
  Taha, M.; Ismail, N. H.; Jamil, W.; Rashwan, H.; Kashif, S. M.; Sain, A. A.; Adenan, M. I.; Anouar, E. H.; Ali, M.; Rahim, F.; Khan, K. M. Eur. J. Med. Chem. 2014, 84, 731. doi: 10.1016/j.ejmech.2014.07.078
5. [5]
  Bouhadir, K. H.; Koubeissi, A.; Mohsen, F. A.; El-Harakeh, M. D.; Cheaib, R.; Younes, J.; Azzi, G.; Eid, A. A. Bioorg. Med. Chem. Lett. 2016, 26, 1020. doi: 10.1016/j.bmcl.2015.12.042
6. [6]
  Uppal, G.; Bala, S.; Kamboj, S.; Saini, M. Pharma Chem. 2011, 3, 250.
7. [7]
  He, H.; Xia, H.; Xia, Q.; Ren, Y.; He, H. Bioorg. Med. Chem. 2017, 25, 5652. doi: 10.1016/j.bmc.2017.08.038
8. [8]
  Feng, Y. X.; Xue, L. W.; Zhang, C. X. J. Chil. Chem. Soc. 2014, 59, 2555. doi: 10.4067/S0717-97072014000300006
9. [9]
  Maddela S.; Ajitha M.; Venugopal M.; Maddela R. Int. J. Pharm. Pharm. Sci. 2014, 6, 254.
10. [10]
  Kumar, V.; Basavarajaswamy, G.; Rai, M. V.; Poojary, B.; Pai, V. R.; Shruthi, N.; Bhat, M. Bioorg. Med. Chem. Lett. 2015, 25, 1420. doi: 10.1016/j.bmcl.2015.02.043
11. [11]
  Mentese, E.; Bekircan, O.; Islamoglu, F.; Beris, F. S. Rev. Chim. (Bucharest, Rom.) 2015, 66, 25.
12. [12]
  Burgeson, J. R.; Gharaibeh, D. N.; Moore, A. L.; Larson, R. A.; Amberg, S. M.; Bolken, T.; Hruby, D. E.; Dai, D. C. Bioorg. Med. Chem. Lett. 2013, 23, 5840. doi: 10.1016/j.bmcl.2013.08.103
13. [13]
  Eldehna, W. M.; Fares, M.; Abdel-Aziz, M. M.; Abdel-Aziz, H. A. Molecules 2015, 20, 8800. doi: 10.3390/molecules20058800
14. [14]
  Velezheva, V.; Brenman, P.; Ivanov, P.; Kornienko, A.; Lyubimov, S.; Kazarian, K.; Nikonenko, B.; Majorov, K.; Apt, A. Bioorg. Med. Chem. Lett. 2016, 26, 978. doi: 10.1016/j.bmcl.2015.12.049
15. [15]
  Torre, S. M. D. D. L.; Vázquez C.; González-Chávez, Z.; Yépez-Mulia, L.; Nieto-Meneses, R.; Jasso-Chávez, R.; Saavedra, E.; Hernández-Luis, F. Bioorg. Med. Chem. Lett. 2017, 27, 3403. doi: 10.1016/j.bmcl.2017.06.013
16. [16]
  Murali, K.; Sparkes, H. A.; Prasad, K. J. R. Eur. J. Med. Chem. 2017, 128, 319. doi: 10.1016/j.ejmech.2017.02.009
17. [17]
  Sun, L. Q.; Wu, Y. B.; Liu, Y. H.; Chen, X. F.; Hu, L. X. Bioorg. Med. Chem. Lett. 2017, 27, 261. doi: 10.1016/j.bmcl.2016.11.068
18. [18]
  Kato, A.; Nagatsuka, Y.; Hitratsuka, T.; Kiuchi, S.; Iwase, Y.; Okuno, Y.; Tsukamoto, T.; Kiran, Y. B.; Sakai, N.; Konakahara, T. Tetrahedron 2016, 72, 4258. doi: 10.1016/j.tet.2016.05.068
19. [19]
  Mahapatra, D. K.; Das, D.; Shivhare, R. Int. J. Pharm. Sci. Drug Res. 2017, 9, 139.
20. [20]
  Itoh, T.; Hatae, N.; Nishiyama, T.; Choshi, T.; Hibino, S.; Yoshimura, T.; Ishikura, M. Med. Chem. Res. 2017, 128, 319.
21. [21]
  Arun, A.; Patel, O. P. S.; Saini, D.; Yadav, P. P.; Konwar, R. Biomed. Pharmacother. 2017, 93, 510. doi: 10.1016/j.biopha.2017.06.065
22. [22]
  Wang, G. C.; Wang, J.; He, D. X.; Li, X.; Li, J.; Peng, Z. Y. Bioorg. Med. Chem. Lett. 2016, 26, 2806. doi: 10.1016/j.bmcl.2016.04.071
23. [23]
  Iqbal, S.; Khan, M. A.; Javaid, K.; Sadiq, R.; Fazal-ur-Rehman, S.; Choudhary, M. I.; Basha, F. Z. Bioorg. Chem. 2017, 74, 72. doi: 10.1016/j.bioorg.2017.07.006
24. [24]
  Börger, C.; Brütting, C.; Julich-Gruner, K. K.; Hesse, R.; Kumar, P.; Kutz, S. K.; Rönnefahrt, M.; Thomas, C.; Wan, B. J.; Franzblau, S. G. Bioorg. Med. Chem. 2017, 25, 6167. doi: 10.1016/j.bmc.2016.12.038
25. [25]
  Chirke, S. S.; Krishna, J. S.; Rathod, B. B.; Bonam, S. R.; Khedkar, V. M.; Rao, B. V.; Kumar, H. M. S.; Shetty, P. R. Med. Chem. Drug Discovery 2017, 2, 7309.
26. [26]
  Kong, X. Q.; Zhang, H. Z.; Cao, C. S.; Zhou, S. L.; Pang, G. S.; Shi, Y.-H. Bioorg. Med. Chem. 2016, 24, 1376. doi: 10.1016/j.bmc.2016.02.013
27. [27]
  Sadiq, Z.; Akbar, E.; Naz, A. N. Int. J. Pharma Bio Sci. 2014, 5, 455.
28. [28]
  Salih, N.; Salimon, J.; Yousif, E. Arabian J. Chem. 2016. 9, S781. doi: 10.1016/j.arabjc.2011.08.013
29. [29]
  Wang, P.-Y.; Fang, H.-S.; Shao, W.-B.; Zhou, J.; Chen, Z.; Song, B.-A.; Yang, S. Bioorg. Med. Chem. Lett. 2017, 27, 4294. doi: 10.1016/j.bmcl.2017.08.040
30. [30]
  Clausen, J. D.; Kjellerup, L.; Cohrt, K. O.; Hansen, J. B.; Dalby-Brown, W.; Winther, A. M. Bioorg. Med. Chem. Lett. 2017, 27, 4564. doi: 10.1016/j.bmcl.2017.08.067
31. [31]
  Wang, W. S.; Li, Q.; Wei, Y. F.; Xue, J.; Sun, X.; Yu, Y.; Chen, Z.; Li, S. Z.; Duan, L.-P. Int. J. Parasitol.:Drugs Drug Resist. 2017, 7, 191. doi: 10.1016/j.ijpddr.2017.03.007
32. [32]
  Wang, W. S.; Li, J.; Yao, J. M.; Wang, T.; Li, S. Z.; Zheng, X. T.; Duan, L. P.; Zhang, W.-B. J. Antimicrob. Chemother. 2017, 72, 3122. doi: 10.1093/jac/dkx250
33. [33]
  Rostom, S. A. F.; Badr, M. H.; Razik, H. A. A. E.; Ashour, H. M. A. Eur. J. Med. Chem. 2017, 139, 263. doi: 10.1016/j.ejmech.2017.07.053
34. [34]
  Sarkis, M.; Miteva, M. A.; Lang, M. C. D.; Jaouen, M.; Sari, M. A.; Galcéra, M. O.; Ethève-Quelquejeu, M.; Garbay, C.; Bertho, G.; Braud, E. Proteins:Struct., Funct., Bioinf. 2013, 21, 7165.
35. [35]
  Lavecchia, A.; Cosconati, S.; Limongelli, V.; Novellino, E. ChemMedChem 2006, 1, 540. doi: 10.1002/(ISSN)1860-7187
36. [36]
  Wang, G. C.; Chen, M.; Qiu, J.; Xie, Z. Z.; Cao, A. B. Bioorg. Med. Chem. Lett. 2018, 28, 113. doi: 10.1016/j.bmcl.2017.11.047
37. [37]
  Lavecchia, A.; Coluccia, A.; Giovanni, C. D.; Novellino, E. Anticancer Agents Med. Chem. 2008, 8, 843. doi: 10.2174/187152008786847783
38. [38]
  Ge, Y.; Kamp, M. V. D.; Malaisree, M.; Liu, D.; Liu, Y.; Mulholland, A. J. J. Comput.-Aided Mol. Des. 2017, 31, 995. doi: 10.1007/s10822-017-0073-y
39. [39]
  Cai, J. Y.; Zhao, L.; Tao, W. Y. Pharm. Biol. 2015, 53, 1030. doi: 10.3109/13880209.2014.957781
40. [40]
  Li, Y. J.; Yu, Y.; Jin, K.; Gao, L. X.; Luo, T. C.; Sheng, L.; Shao, X.; Li, J. Bioorg. Med. Chem. Lett. 2014, 24, 4125. doi: 10.1016/j.bmcl.2014.07.055
41. [41]
  Li, Y.-J.; Shi, X.-L.; Gao, L.-X.; Jin, K.; Sheng, L.; Wu, J.-H.; Peng, L.-N.; Li, J. Chin. J. Org. Chem. 2015, 35, 191(in Chinese).
42. [42]
  Li, Y.-J.; Yu, Y.; Jin, K.; Gao, L.-X.; Luo, T.-C.; Sheng, L.; Shao, X.; Li, J. Chin. J. Org. Chem. 2015, 35, 129(in Chinese).
43. [43]
  Li, Y.-J.; Li, J.-Y.; Peng, L.-N.; Gao, L.-X.; Jin, K.; Sheng, L.; Zhang, N.; Wang, S.-Y.; Li, J. Chin. J. Org. Chem. 2017, 37, 485(in Chinese).
44. [44]
  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).
45. [45]
  Kahveci, B.; Yılmaz, F.; Menteşe, E.; Özil, M.; Karaoğlu, Ş. A. J. Heterocycl. Chem. 2014, 51, 982. doi: 10.1002/jhet.v51.4
46. [46]
  Bayrak, H.; Demirbas, A.; Karaoglu, S. A.; Demirbas, N. Eur. J. Med. Chem. 2009, 44, 1057. doi: 10.1016/j.ejmech.2008.06.019
47. [47]
  Zhou, M.; Eun, Y. J.; Guzei, I. A.; Weibel, D. B. ACS Med. Chem. Lett. 2013, 4, 880. doi: 10.1021/ml400234x
48. [48]
  Li, Y.-J.; Li, J.-Y.; Jin, K.; Cao, X. Chin. J. Magn. Reson. 2017, 34, 25(in Chinese). doi: 10.11938/cjmr20170104
49. [49]
  Li, Y.-J.; Li, J.-Y.; Xu, Y.-T.; Jin, K.; Cao, X. Chin. J. Org. Chem. 2017, 37, 896(in Chinese).
50. [50]
  Guo, D. C.; Li, P. L.; Wang, X.; Wang, L. Y.; Wu, P. L. Synth. Commun. 2010, 40, 3315. doi: 10.1080/00397910903419811
51. [51]
  Li, Y.-J.; Sun, S.-Q. Semimicro Organic Chemistry Experiment, Chemical Industry Press, Beijing, 2009, pp. 114~115(in Chinese).
52. [52]
  Li, Y.-J.; Zhang, N.; Jin, K.; Xu, Y.-T.; Wang, S.-Y.; Zhou, X.-X. Chin. J. Org. Chem. 2017, 37, 2640(in Chinese).
53. [53]
  Huang, W. G.; Jiang, Y. Y.; Li, Q.; Li, J.; Li, J. Y.; Lu, W.; Cai, J. C. Tetrahedron 2005, 61, 1863. doi: 10.1016/j.tet.2004.12.033
54. [54]
  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. doi: 10.1016/j.ejmech.2011.05.027
1. [1]
  Zhi Zhou , Yu-E Lian , Yuqing Li , Hui Gao , Wei Yi . New Insights into the Molecular Mechanism Behind Clinical Tragedies of “Cephalosporin with Alcohol”. University Chemistry, 2025, 40(3): 42-51. doi: 10.12461/PKU.DXHX202403104
2. [2]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
3. [3]
  Xinting XIONG , Zhiqiang XIONG , Panlei XIAO , Xuliang NIE , Xiuying SONG , Xiuguang YI . Synthesis, crystal structures, Hirshfeld surface analysis, and antifungal activity of two complexes Na(Ⅰ)/Cd(Ⅱ) assembled by 5-bromo-2-hydroxybenzoic acid ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1661-1670. doi: 10.11862/CJIC.20240145
4. [4]
  Jiaming Xu , Yu Xiang , Weisheng Lin , Zhiwei Miao . Research Progress in the Synthesis of Cyclic Organic Compounds Using Bimetallic Relay Catalytic Strategies. University Chemistry, 2024, 39(3): 239-257. doi: 10.3866/PKU.DXHX202309093
5. [5]
  Jingjie Tang , Luying Xie , Jiayu Liu , Shangyu Shi , Xinyu Sun , Jiayang Lin , Qikun Yang , Chuan'ang Yu , Zecheng Wang , Yingying Wang , Zengyang Xie . Efficient Rapid Synthesis and Antibacterial Activities of Tosylhydrazones: A Recommended Innovative Chemistry Experiment for Undergraduate Medical University. University Chemistry, 2024, 39(3): 316-326. doi: 10.3866/PKU.DXHX202309091
6. [6]
  Yonghui ZHOU , Rujun HUANG , Dongchao YAO , Aiwei ZHANG , Yuhang SUN , Zhujun CHEN , Baisong ZHU , Youxuan ZHENG . Synthesis and photoelectric properties of fluorescence materials with electron donor-acceptor structures based on quinoxaline and pyridinopyrazine, carbazole, and diphenylamine derivatives. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 701-712. doi: 10.11862/CJIC.20230373
7. [7]
  Lirui Shen , Kun Liu , Ying Yang , Dongwan Li , Wengui Chang . Synthesis and Application of Decanedioic Acid-N-Hydroxysuccinimide Ester: Exploration of Teaching Reform in Comprehensive Applied Chemistry Experiment. University Chemistry, 2024, 39(8): 212-220. doi: 10.3866/PKU.DXHX202312035
8. [8]
  Yuhao SUN , Qingzhe DONG , Lei ZHAO , Xiaodan JIANG , Hailing GUO , Xianglong MENG , Yongmei GUO . Synthesis and antibacterial properties of silver-loaded sod-based zeolite. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 761-770. doi: 10.11862/CJIC.20230169
9. [9]
  Rui Gao , Ying Zhou , Yifan Hu , Siyuan Chen , Shouhong Xu , Qianfu Luo , Wenqing Zhang . Design, Synthesis and Performance Experiment of Novel Photoswitchable Hybrid Tetraarylethenes. University Chemistry, 2024, 39(5): 125-133. doi: 10.3866/PKU.DXHX202310050
10. [10]
  Zhifang SU , Zongjie GUAN , Yu FANG . Process of electrocatalytic synthesis of small molecule substances by porous framework materials. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2373-2395. doi: 10.11862/CJIC.20240290
11. [11]
  Zhenhua Wang , Haoyang Feng , Xiaoyang Shao , Wenru Fan . Vitamins in Solid Propellants: Controlled Synthesis of Neutral Macromolecular Bonding Agents. University Chemistry, 2025, 40(4): 1-9. doi: 10.3866/PKU.DXHX202401007
12. [12]
  Huijuan Liao , Yulin Xiao , Dong Xue , Mingyu Yang , Jianyang Dong . Synthesis of 1-Benzyl Isoquinoline via the Minisci Reaction. University Chemistry, 2025, 40(7): 294-299. doi: 10.12461/PKU.DXHX202409092
13. [13]
  Yufang GAO , Nan HOU , Yaning LIANG , Ning LI , Yanting ZHANG , Zelong LI , Xiaofeng LI . Nano-thin layer MCM-22 zeolite: Synthesis and catalytic properties of trimethylbenzene isomerization reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1079-1087. doi: 10.11862/CJIC.20240036
14. [14]
  Yihui Song , Shangshang Qin , Kai Wu , Chengyun Jin , Bin Yu . 生物化学在高水平创新型药学人才培养中的交叉融合应用——以去甲基化酶LSD1抑制剂的活性评价为例. University Chemistry, 2025, 40(6): 341-352. doi: 10.12461/PKU.DXHX202406018
15. [15]
  Yinwu Su , Xuanwen Zheng , Jianghui Du , Boda Li , Tao Wang , Zhiyan Huang . Green Synthesis of 1,3-Dibromoacetone Using Halogen Exchange Method: Recommending a Basic Organic Synthesis Teaching Experiment. University Chemistry, 2024, 39(5): 307-314. doi: 10.3866/PKU.DXHX202311092
16. [16]
  Tianyun Chen , Ruilin Xiao , Xinsheng Gu , Yunyi Shao , Qiujun Lu . Synthesis, Crystal Structure, and Mechanoluminescence Properties of Lanthanide-Based Organometallic Complexes. University Chemistry, 2024, 39(5): 363-370. doi: 10.3866/PKU.DXHX202312017
17. [17]
  Jiying Liu , Zehua Li , Wenjing Zhang , Donghui Wei . Molecular Orbital and Nucleus-Independent Chemical Shift Calculations for C₆H₆ and B₁₂H₁₂^2-: A Computational Chemistry Experiment. University Chemistry, 2025, 40(3): 186-192. doi: 10.12461/PKU.DXHX202406085
18. [18]
  Tingyu Zhu , Hui Zhang , Wenwei Zhang . Exploration and Practice of Ideological and Political Education in the Course of Experiments on Chemical Functional Molecules: Synthesis and Catalytic Performance Study of Chiral Mn(III)Cl-Salen Complex. University Chemistry, 2024, 39(4): 75-80. doi: 10.3866/PKU.DXHX202311011
19. [19]
  Yuanyuan Ping , Wangqing Kong . 光催化碳氢键官能团化合成1-苯基-1,2-乙二醇. University Chemistry, 2025, 40(6): 238-247. doi: 10.12461/PKU.DXHX202408092
20. [20]
  Zhuo Wang , Xue Bai , Kexin Zhang , Hongzhi Wang , Jiabao Dong , Yuan Gao , Bin Zhao . MOF模板法合成氮掺杂碳材料用于增强电化学钠离子储存和去除. Acta Physico-Chimica Sinica, 2025, 41(3): 2405002-. doi: 10.3866/PKU.WHXB202405002

Get Citation

PDF

XML

Metrics

PDF Downloads(8)
Abstract views(1168)
HTML views(110)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142