Citation: Hu Hongyu, Wu Jun, Yuan Jianfeng, Wang Zhenni, Li Chenfan, Yan Xiaoyan, Fang Meijuan, Zhao Shengxian. Synthesis and Biological Activity Research of 4-Substitued-1-(2-methyl-6-(pyridin-3-yl)-nicotinoyl) Semicarbazides[J]. Chinese Journal of Organic Chemistry, ;2019, 39(9): 2507-2514. doi: 10.6023/cjoc201902033 shu

Synthesis and Biological Activity Research of 4-Substitued-1-(2-methyl-6-(pyridin-3-yl)-nicotinoyl) Semicarbazides

Hu Hongyu ^a,† ,
Wu Jun ^b,† ,
Yuan Jianfeng ^a ,
Wang Zhenni ^a ,
Li Chenfan ^a ,
Yan Xiaoyan ^a ,
Fang Meijuan ^b,, ,
Zhao Shengxian ^a,c,,

a.
Xingzhi College, Zhejiang Normal University, Jinhua 321004
b.
School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102
c.
College of Science and Technology, Ningbo University, Cixi 315302

Corresponding author: Fang Meijuan, fangmj@xmu.edu.cn Zhao Shengxian, 2086488660@qq.com
Received Date: 27 February 2019
Revised Date: 10 April 2019
Available Online: 10 September 2019
Fund Project: Project supported by the General Research Projects of Zhejiang Provincial Department of Education (No. Y201941989)the General Research Projects of Zhejiang Provincial Department of Education Y201941989

Figures(4)

A series of 4-substitued-1-(2-methyl-6-(pyridin-3-yl)-nicotinoyl) semicarbazides were synthesized via molecular hybridization strategy. The synthesized compounds were screened for their anticancer potential against different cancer cells viz human hepatocelular carcinoma (QGY-7703), non-small cell lung (NCl-H460) and human breast (MCF-7) cancer cell lines by methyl thiazolyl tetrazolium (MTT) assay. 1-(2-Methyl-6-(pyridin-3-yl)nicotinoyl)-4-(2, 4, 6-trichlorophenyl)semicarbazide (4n) showed significant anticancer activity in these cancer cell lines with a range of IC₅₀ values from 8.89 μmol/L to 11.45 μmol/L. Further biology studies showed that 4n treatment obviously increased the level of cleaved PARP and induced the apoptosis in QGY-7703 cells.
- semicarbazides,
- bipyridine,
- molecular hybridization,
- biological activity
1. [1]
  Lozano, R.; Naghavi, M.; Foreman, K.; Lim, S.; Shibuya, K.; Aboyans, K.; Abraham, J.; Adair, T.; Aggarwal, R.; Ahn, S. Y.; AlMazroa, M. A.; Alvarado, M.; Anderson, H. R.; Anderson, L. M.; Andrews, K. G.; Atkinson, C.; Baddour, L. M.; Barker-Collo, S.; Bartels, D. H.; Bell, M. L.; Benjamin, E. J.; Bennett, D.; Bhalla, K.; Bikbov, B.; Abdulhak, A. B.; Birbeck, G.; Blyth, F.; Bolliger, I.; Boufous, S.; Bucello, C.; Burch, M.; Burney, P.; Carapetis, J.; Chen, H. L.; Chou, D.; Chugh, S. S.; Coffeng, L. E.; Colan, S. D.; Colquhoun, S.; Colson, K. E.; Condon, J.; Connor, M. D.; Cooper, L. T.; Corriere, M.; Cortinovis, M.; Vaccaro, K.C. D.; Couser, W.; Cowie, B. C.; Criqui, M. H.; Cross, M.; Dabhadkar, K. C.; Dahodwala, N.; Leo, D. D.; Degenhardt, L.; Delossantos, A.; Denenberg, J.; Jarlais, D. C. D.; Dharmaratne, S. D.; Dorsey, E. R.; Driscoll, T.; Duber, H.; Ebel, B.; Erwin, P. J.; Espindola, P.; Ezzati, M.; Feigin, V.; Flaxman, A. D.; Forouzanfar, M. H.; Fowkes, F. G. R.; Franklin, R.; Fransen, M.; Freeman, M. K.; Gabriel, S. E.; Gakidou, E.; Gaspari, F.; Gillum, R. F.; Gonzalez-Medina, D.; Halasa, Y. A.; Haring, D.; Harrison, J. E.; Havmoeller, R.; Hay, R. J.; Hoen, B.; Hotez, P. J; Hoy, D.; Jacobsen, K. H.; James, S. L.; Jasrasaria, R.; Jayaraman, S.; Johns, N.; Karthikeyan, G.; Kassebaum, N.; Keren, A.; Khoo, J.; Knowlton, L. M.; Kobusingye, O.; Koranteng, A.; Krishnamurthi, R.; Lipnick, M.; Lipshultz, S. E.; Ohno, S. L.; Mabweijano, J.; MacIntyre, M. F.; Mallinger, L.; March, L.; Marks, G. B.; Marks, R.; Matsumori, A.; Matzopoulos, R.; Mayosi, B. M.; McAnulty, J. H.; McDermott, M. M.; McGrath, J.; Memish, Z. A.; Mensah, G. A.; Merriman, T. R.; Michaud, C.; Miller, M.; Miller, T. R.; Mock, C.; Mocumbi, A. O.; Mokdad, A. A.; Moran, A.; Mulholland, K.; Nair, M. N.; Naldi, L.; Narayan, K. M. V.; Nasseri, K.; Norman, P.; O'Donnell, M.; Omer, S. B.; Ortblad, K.; Osborne, R.; Ozgediz, D.; Pahari, B.; Pandian, J. D.; Rivero, A. P.; Padilla, R. P.; Perez-Ruiz, F.; Perico, N.; Phillips, D.; Pierce, K.; Pope Ⅲ, C. A.; Porrini, E.; Pourmalek, F.; Raju, M.; Ranganathan, D.; Rehm, J. T.; Rein, D. B.; Remuzzi, G.; Rivara, F. P.; Roberts, T.; León, F. R. D.; Rosenfeld, L. C.; Rushton, L.; Sacco, R. L.; Salomon, J. A.; Sampson, U.; Sanman, E.; Schwebel, D. C.; Segui-Gomez, M.; Shepard, D. S.; Singh, D.; Singleton, J.; Sliwa, K.; Smith, E.; Steer, A.; Taylor, J. A.; Thomas, B.; Tleyjeh, I. M.; Towbin, J. A.; Truelsen, T.; Undurraga, E. A.; Venketasubramanian, N.; Vijayakumar, L.; Vos, T.; Wagner, G. A.; Wang, M. R.; Wang, W. Z.; Watt, K.; Weinstock, M. A.; Weintraub, R.; Wilkinson, J. D.; Woolf, A. D.; Wulf, S.; Yeh, P. H.; Yip, P.; Zabetian, A.; Zheng, Z. J.; Lopez, A. D.; Murray, C. J. L. Lancet 2012, 380, 2095.
2. [2]
  Guo, Z. H.; Du, Q.; Dai, X. C.; Liu, Y. Y.; Yu, B.; Zhai, Q. Shanghai Med. Pharm. J. 2018, 39, 5.
3. [3]
  Thomas, K. D.; Adhikari, A. V.; Telkar, S.; Chowdhury, I. H.; Mahmood, R.; Pal, N. K.; Row, G.; Sumesh, E. Eur. J. Med. Chem. 2011, 46, 5283. doi: 10.1016/j.ejmech.2011.07.033
4. [4]
  Deng, X. Q.; Wei, C. X.; Li, F. N.; Sun, Z. G.; Quan, Z. S. Eur. J. Med. Chem. 2010, 45, 3080. doi: 10.1016/j.ejmech.2010.03.041
5. [5]
  Hameed, P. S.; Solapurel, S.; Patill, V.; Henrich, P. P.; Magistrado, P. A.; Bharath, S.; Murugan, K.; Viswanath, P.; Puttur, J.; Srivastava, A.; Bellale, E.; Panduga, V.; Shanbag, G.; Awasthy, D.; Landge, S.; Morayya, S.; Koushik, K.; Saralaya, R.; Raichurkar, A.; Rautela, N.; Choudhury, N. R.; Ambady, A.; Nandishaiah, R.; Reddy, J.; Prabhakar, K. R.; Menasinakai, S.; Rudrapatna, S.; Chatterji, M.; Jimenez-Diaz, M. B.; Martinez, M. S.; Sanz, L. M.; Coburn-Flynn, O.; Fidock, D. A.; Lukens, A. K.; Wirth, D. F.; Bandodkar, B.; Mukherjee, K.; McLaughlin, R. E.; Waterson, D.; Rosenbrier-Ribeiro, L.; Hickling, K.; Balasubramanian, V.; Warner, P.; Hosagrahara, V.; Dudley, A.; Iyer, P. S.; Narayanan, S.; Kavanagh, S.; Sambandamurthy, V. K. Nat. Commun. 2015, 6, 1.
6. [6]
  Guo, B.; Fan, H. X.; Xin, Q. S.; Chu, W. J.; Wang, H.; Huang, Y. Q.; Chen, X. Y.; Yang, Y. S. J. Med. Chem. 2013, 56, 2642. doi: 10.1021/jm4000598
7. [7]
  Grigor'ev, A. A.; Shtyrlin, N. V.; Gabbasova, R. R.; Zeldi, M. I.; Grishaev, D. Y.; Gnezdilov, O. I.; Balakin, K. V.; Nasakin, O. E.; Shtyrlin, Y. G. Synth. Commun. 2018, 48, 2288. doi: 10.1080/00397911.2018.1501487
8. [8]
  Lan, L.; Zhan, X. P.; Qin, W. X.; Liu, Z. L.; Mao, Z. M. Heterocycles 2014, 89, 375. doi: 10.3987/COM-13-12890
9. [9]
  Łukowska-Chojnacka, E.; Wińska, P.; Wielechowska, M.; Poprzeczko, M.; Bretner, M. Bioorg. Med. Chem. 2016, 24, 735. doi: 10.1016/j.bmc.2015.12.041
10. [10]
  Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Valori, L.; Landi, L.; Prata, C.; Berridge, M. V.; Grasso, C.; Fiebig, H.; Kelter, G.; Burger, A. M.; Kunkel, M. W. J. Med. Chem. 2008, 51, 4563. doi: 10.1021/jm800194k
11. [11]
  Zhang, S.; Luo, Y.; He, L. Q.; Liu, Z. J.; Jiang, A. Q.; Yang, Y. H.; Zhu, H. L. Bioorg. Med. Chem. 2013, 21, 3723. doi: 10.1016/j.bmc.2013.04.043
12. [12]
  Song, K. Z.; Ma, J. J.; Wang, X.; Gong, P.; Zhao, Y. F. Chem. Res. Chin. Univ. 2014, 30, 75. doi: 10.1007/s40242-013-3281-6
13. [13]
  Viegas-Junior, C.; Danuello, A.; Bolzani, V. D. S.; Barreiro, E. J.; Fraga, C. A. M. Curr. Med. Chem. 2007, 14, 1829. doi: 10.2174/092986707781058805
14. [14]
  Fortin, S.; Bérubé, G. Expert Opin. Drug Discovery 2013, 8, 1029. doi: 10.1517/17460441.2013.798296
15. [15]
  El-Sadek, M. E.; Aboukull, M. E.; El-Sabbagh, O. I.; Shallal, H. M. Pharm. Chem. J. 2007, 41, 188. doi: 10.1007/s11094-007-0043-0
16. [16]
  Hu, H. Y.; Wu, J.; Ao, M. T.; Wang, H.; Zhou, T. T.; Xue, Y. H.; Qiu, H. K.; Fan, M. J.; Wu, Z. Chem. Biol. Drug Des. 2016, 88, 766. doi: 10.1111/cbdd.12808
17. [17]
  Hu, H. Y.; Yu, X. D.; Wang, F.; Lin, C. R.; Zeng, J. Z.; Qiu, Y. K.; Fang, M. J.; Wu, Z. Molecules 2016, 21, 530. doi: 10.3390/molecules21050530
18. [18]
  Hu, H. Y.; Lin, C. R.; Ao, M. T.; Ji, Y. F.; Tang, B. W.; Zhou, X. X.; Fang, M. J.; Zeng, J. Z.; Wu, Z. RSC Adv. 2017, 7, 51640. doi: 10.1039/C7RA08149A
1. [1]
  Xin MA , Ya SUN , Na SUN , Qian KANG , Jiajia ZHANG , Ruitao ZHU , Xiaoli GAO . A Tb₂ complex based on polydentate Schiff base: Crystal structure, fluorescence properties, and biological activity. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1347-1356. doi: 10.11862/CJIC.20230357
2. [2]
  Tao Yu , Vadim A. Soloshonok , Zhekai Xiao , Hong Liu , Jiang Wang . Probing the dynamic thermodynamic resolution and biological activity of Cu(Ⅱ) and Pd(Ⅱ) complexes with Schiff base ligand derived from proline. Chinese Chemical Letters, 2024, 35(4): 108901-. doi: 10.1016/j.cclet.2023.108901
3. [3]
  Hao Jiang , Yuan-Yuan He , Hai-Chao Liang , Meng-Jia Shang , Han-Han Lu , Chun-Hua Liu , Yin-Shan Meng , Tao Liu , Yuan-Yuan Zhu . Tuning lanthanide luminescence from bipyridine-bis(oxazoline/thiazoline) tetradentate ligands. Chinese Journal of Structural Chemistry, 2024, 43(9): 100354-100354. doi: 10.1016/j.cjsc.2024.100354
4. [4]
  Hualei Xu , Manman Han , Haiqiang Liu , Liang Qin , Lulu Chen , Hao Hu , Ran Wu , Chenyu Yang , Hua Guo , Jinrong Li , Jinxiang Fu , Qichen Hao , Yijun Zhou , Jinchao Feng , Xiaodong Wang . 4-Nitrocatechol as a novel matrix for low-molecular-weight compounds in situ detection and imaging in biological tissues by MALDI-MSI. Chinese Chemical Letters, 2024, 35(6): 109095-. doi: 10.1016/j.cclet.2023.109095
5. [5]
  Jian Song , Shenghui Wang , Qiuge Liu , Xiao Wang , Shuo Yuan , Hongmin Liu , Saiyang Zhang . N-Benzyl arylamide derivatives as novel and potent tubulin polymerization inhibitors against gastric cancers: Design, structure–activity relationships and biological evaluations. Chinese Chemical Letters, 2025, 36(2): 109678-. doi: 10.1016/j.cclet.2024.109678
6. [6]
  Kai An , Qinglong Qiao , Lovelesh , Syed Ali Abbas Abedi , Xiaogang Liu , Zhaochao Xu . "Superimposed" spectral characteristics of fluorophores arising from cross-conjugation hybridization. Chinese Chemical Letters, 2025, 36(1): 109786-. doi: 10.1016/j.cclet.2024.109786
7. [7]
  Jialiang XU , Jiabin CUI . Recent biological applications of corroles: From diagnosis to therapy. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2303-2317. doi: 10.11862/CJIC.20240245
8. [8]
  Fang-Yuan Chen , Wen-Chao Geng , Kang Cai , Dong-Sheng Guo . Molecular recognition of cyclophanes in water. Chinese Chemical Letters, 2024, 35(5): 109161-. doi: 10.1016/j.cclet.2023.109161
9. [9]
  Kuan Deng , Fei Yang , Zhi-Qi Cheng , Bi-Wen Ren , Hua Liu , Jiao Chen , Meng-Yao She , Le Yu , Xiao-Gang Liu , Hai-Tao Feng , Jian-Li Li . Construction of wavelength-tunable DSE quinoline salt derivatives by regulating the hybridization form of the nitrogen atom and intramolecular torsion angle. Chinese Chemical Letters, 2024, 35(10): 109464-. doi: 10.1016/j.cclet.2023.109464
10. [10]
  Bin Chen , Chaoyang Zheng , Dehuan Shi , Yi Huang , Renxia Deng , Yang Wei , Zheyuan Liu , Yan Yu , Shenghong Zhong . p-d orbital hybridization induced by CuGa2 promotes selective N2 electroreduction. Chinese Journal of Structural Chemistry, 2025, 44(1): 100468-100468. doi: 10.1016/j.cjsc.2024.100468
11. [11]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
12. [12]
  Zikang Hu , Hengjie Zhang , Zhengqiu Li , Tianbao Zhao , Zhipeng Gu , Qijuan Yuan , Baoshu Chen . Multifunctional photothermal hydrogels: Design principles, various functions, and promising biological applications. Chinese Chemical Letters, 2024, 35(10): 109527-. doi: 10.1016/j.cclet.2024.109527
13. [13]
  Caihong Mao , Yanfeng He , Xiaohan Wang , Yan Cai , Xiaobo Hu . Synthesis and molecular recognition characteristics of a tetrapodal benzene cage. Chinese Chemical Letters, 2024, 35(8): 109362-. doi: 10.1016/j.cclet.2023.109362
14. [14]
  Cheng-Da Zhao , Huan Yao , Shi-Yao Li , Fangfang Du , Li-Li Wang , Liu-Pan Yang . Amide naphthotubes: Biomimetic macrocycles for selective molecular recognition. Chinese Chemical Letters, 2024, 35(4): 108879-. doi: 10.1016/j.cclet.2023.108879
15. [15]
  Guangyao Wang , Zhitong Xu , Ye Qi , Yueguang Fang , Guiling Ning , Junwei Ye . Electrospun nanofibrous membranes with antimicrobial activity for air filtration. Chinese Chemical Letters, 2024, 35(10): 109503-. doi: 10.1016/j.cclet.2024.109503
16. [16]
  Gang Lang , Jing Feng , Bo Feng , Junlan Hu , Zhiling Ran , Zhiting Zhou , Zhenju Jiang , Yunxiang He , Junling Guo . Supramolecular phenolic network-engineered C–CeO₂ nanofibers for simultaneous determination of isoniazid and hydrazine in biological fluids. Chinese Chemical Letters, 2024, 35(6): 109113-. doi: 10.1016/j.cclet.2023.109113
17. [17]
  Mianling Yang , Meehyein Kim , Peng Zhan . Modular miniaturized synthesis and in situ biological evaluation facilitate rapid discovery of potent MraY inhibitors as antibacterial agents. Chinese Chemical Letters, 2025, 36(2): 110455-. doi: 10.1016/j.cclet.2024.110455
18. [18]
  Shuaige Bai , Shuai Huang , Ting Luo , Bin Feng , Yanpeng Fang , Feiyi Chu , Jie Dong , Wenbin Zeng . Debut of a responsive chemiluminescent probe for butyrylcholinesterase: Application in biological imaging and pesticide residue detection. Chinese Chemical Letters, 2025, 36(3): 110054-. doi: 10.1016/j.cclet.2024.110054
19. [19]
  Zhimin Sun , Xin-Hui Guo , Yue Zhao , Qing-Yu Meng , Li-Juan Xing , He-Lue Sun . Dynamically switchable porphyrin-based molecular tweezer for on−off fullerene recognition. Chinese Chemical Letters, 2024, 35(6): 109162-. doi: 10.1016/j.cclet.2023.109162
20. [20]
  Li Lin , Song-Lin Tian , Zhen-Yu Hu , Yu Zhang , Li-Min Chang , Jia-Jun Wang , Wan-Qiang Liu , Qing-Shuang Wang , Fang Wang . Molecular crowding electrolytes for stabilizing Zn metal anode in rechargeable aqueous batteries. Chinese Chemical Letters, 2024, 35(7): 109802-. doi: 10.1016/j.cclet.2024.109802

Get Citation

PDF

XML

Metrics

PDF Downloads(9)
Abstract views(679)
HTML views(48)

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