Citation: Ma Hongguang, Wang Liping, Xu Zhihong, Zhang Yapeng, Li Xia, Zhu Weiming. Synthesis and Cytotoxicity of N₁₂-Ethyl Substituted Indolocarbazole Derivatives[J]. Chinese Journal of Organic Chemistry, ;2016, 36(8): 1839-1846. doi: 10.6023/cjoc201602035 shu

Synthesis and Cytotoxicity of N₁₂-Ethyl Substituted Indolocarbazole Derivatives

Ma Hongguang ^a ,
Wang Liping ^b ,
Xu Zhihong ^a ,
Zhang Yapeng ^a ,
Li Xia ^c ,
Zhu Weiming ^a,*,,

a.
Key Laboratory of Marine Drugs, Ministry Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003
b.
Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002
c.
School of Ocean, Shandong University, Weihai 264209

Corresponding author: Zhu Weiming, weimingzhu@ouc.edu.cn
Received Date: 29 February 2016
Revised Date: 17 April 2016

Fund Project: Project supported by the National Natural Science Foundation of China Nos. 81561148012，41376148，81273532，30973680and the National Natural Science Foundation of China-Guangdong Fund Joint Project No. U1501221the National High-Tech R & D Program of China No. 2012AA092104

Figures(1)

Nine new N₁₂-ethyl substituted indolocarbazole derivatives were synthesized. Their structures were identified by ¹H NMR, ¹³C NMR and HRESIMS. The thiazolyl blue tetrazolium bromide (MTT) method was used to evaluate the cytotoxicities of these derivatives against A549, HepG-2 and Hela cell lines, while the cell counting kit-8 (CCK-8) method was used to evaluate cytotoxicity against K562 cell lines. The results showed that compounds 7～9 displayed comparable cytotoxicity to adriamycin (ADM) against K562 cell lines with the IC₅₀ values of 0.43～0.93 μmol/L. Compounds 8 and 12 showed comparable cytotoxicity to ADM against Hela cell lines with the IC₅₀ values of 1.23 and 0.43 μmol/L, respectively. The hydrochloride 14 of compound 13 exhibited good cytotoxicity against the four cell lines with the IC₅₀ values of 0.23～1.72 μmol/L, indicating a worth of further study as an antitumor lead compound.
- N₁₂-ethyl indolocarbazole,
- synthesis,
- cytotoxicity
1. [1]
2. [2]
  Ma, H.; Liu, Q.; Zhu, G.; Liu, H.; Zhu, W. J. Asian Nat. Prod. Res. 2016, 18, 92.
3. [3]
4. [4]
5. [5]
  Omura, S.; Iwai, Y.; Hirano, A.; Nakagawa, A.; Awaya, J.; Tsuchiya, H.; Takahashi, Y.; Masuma, R. J. Antibiot. 1977, 30, 275.
6. [6]
7. [7]
  Wang, L.; Mei, X.; Wang, C.; Zhu, W. Tetrahedron 2015, 71, 7990.
8. [8]
  Gani, O. A.; Engh, R. A. Nat. Prod. Rep. 2010, 27, 489.
9. [9]
  Sánchez, C.; Méndez, C.; Salas, J. A. Nat. Prod. Rep. 2006, 23, 1007.
10. [10]
  Fu, P.; Zhuang, Y.; Wang, Y.; Liu, P.; Qi, X.; Gu, K.; Zhang, D.; Zhu, W. Org. Lett. 2012, 14, 6194.
11. [11]
  Fu, P.; Yang, C.; Wang, Y.; Liu, P.; Ma, Y.; Xu, L.; Su, M.; Hong, K.; Zhu, W. Org. Lett. 2012, 14, 2422.
12. [12]
  Pereira, E. R.; Belin, L.; Sancelme, M.; Prudhomme, M.; Ollier, M.; Rapp, M.; Severe, D.; Riou, J. F.; Fabbro, D.; Meyer, T. J. Med. Chem. 1996, 39, 4471.
13. [13]
  Labourier, E.; Riou, J. F.; Prudhomme, M.; Carrasco, C.; Bailly, C.; Tazi, J. Cancer Res. 1999, 59, 52.
14. [14]
  Zhu, G. X.; Conner, S. E.; Zhou, X.; Chan, H. K.; Shih, C.; Engler, T. A.; Al-Awar, R. S.; Brooks, H. B.; Watkins, S. A.; Spencer, C. D.; Schultz, R. M.; Dempsey, J. A.; Considine, E. L.; Patel, B. R.; Ogg, C. A.; Vasudevan, V.; Lytle, M. L. Bioorg. Med. Chem. Lett. 2004, 14, 3057.
15. [15]
  Zhang, H. C.; White, K. B.; Ye, H.; McComsey, D. F.; Derian, C. K.; Addo, M. F.; Andrade-Gordon, P.; Eckardt, A. J.; Conway, B. R.; Westover, L.; Xu, J. Z.; Look, R.; Demarest, K. T.; Emanuel, S.; Maryanoff, B. E. Bioorg. Med. Chem. Lett. 2003, 13, 3049.
16. [16]
  Rodriguez-Ariza, A.; Lopez-Pedrera, C.; Aranda, E.; Barbarroja, N. Crit. Rev. Oncol. Hematol. 2011, 80, 241.
17. [17]
  Hudkins, R. L.; Becknell, N. C.; Zulli, A. L.; Underiner, T. L.; Angeles, T. S.; Aimone, L. D.; Albom, M. S.; Chang, H.; Miknyoczki, S. J.; Hunter, K.; Jones-Bolin, S.; Zhao, H.; Bacon, E. R.; Mallamo, J. P.; Ator, M. A.; Ruggeri, B. A. J. Med. Chem. 2012, 55, 903.
18. [18]
  Ruegg, U. T.; Burgess, G. M. Trends Pharmacol. Sci. 1989, 10, 218.
19. [19]
  Bharate, S. B.; Sawant, S. D.; Singh, P. P.; Vishwakarma, R. A. Chem. Rev. 2013, 113, 6761.
20. [20]
  Anastassiadis, T.; Deacon, S. W.; Devarajan, K.; Ma, H.; Peterson, J. R. Nat. Biotechnol. 2011, 29, 1039.
21. [21]
  Huang, Y. C.; Chao, D. K.; Chao, K. S. C.; Chen, Y. J. Toxicol. In Vitro 2009, 23, 979.
22. [22]
  Del Corral, A.; Dutreix, C.; Huntsman-Labed, A.; Lorenzo, S.; Morganroth, J.; Harrell, R.; Wang, Y. Cancer Chemother. Pharmacol. 2012, 69, 1255.
23. [23]
  Fischer, T.; Stone, R. M.; Deangelo, D. J.; Galinsky, I.; Estey, E.; Lanza, C.; Fox, E.; Ehninger, G.; Feldman, E. J.; Schiller, G. J.; Klimek, V. M.; Nimer, S. D.; Gilliland, D. G.; Dutreix, C.; Huntsman-Labed, A.; Virkus, J.; Giles, F. J. J. Clin. Oncol. 2010, 28, 4339.
24. [24]
  Graul, A. I. Drug News Perspect. 2007, 20, 45.
25. [25]
  Levis, M.; Allebach, J.; Tse, K. F., Zheng, R.; Baldwin, B. R.; Smith, B. D.; Jones-Bolin, S.; Ruggeri, B.; Dionne, C.; Small, D. Blood 2002, 99, 3885.
26. [26]
  Diaz, T.; Navarro, A.; Ferrer, G.; Gel, B.; Gaya, A.; Artells, R.; Bellosillo, B.; Garcia-Garcia, M.; Serrano, S.; Martínez, A.; Monzo, M. PLoS One 2011, 6, e18856.
27. [27]
  Marshall, J. L.; Kindler, H.; Deeken, J.; Bhargava, P.; Vogelzang, N. J.; Rizvi, N.; Luhtala, T.; Boylan, S.; Dordal, M.; Robertson, P.; Hawkins, M. J.; Ratain, M. J. Invest New Drugs 2005, 23, 31.
28. [28]
  Knapper, S.; Burnett, A. K.; Littlewood, T.; Kell, W. J.; Agrawal, S.; Chopra, R.; Clark, R.; Levis, M. J.; Small, D. Blood 2006, 108, 3262.
29. [29]
  Mackay, H. J.; Twelves, C. J. Nat. Rev. Cancer 2007, 7, 554.
30. [30]
  Lee, K. W.; Kim, S. G.; Kim, H. P.; Kwon, E.; You, J.; Choi, H. J.; Park, J. H.; Kang, B. C.; Im, S. A.; Kim, T. Y.; Kim, W. H.; Bang, Y. J. Cancer Res. 2008, 68, 1916.
31. [31]
  Padda, S. K.; Krupitskaya, Y.; Chhatwani, L.; Fisher, G. A.; Colevas, A. D.; Pedro-Salcedo, M. S.; Decker, R.; Latz, J. E.; Wakelee, H. A. Cancer Chemother. Pharmacol. 2012, 69, 1013.
32. [32]
  Slater, M. J.; Baxter, R.; Bonser, R. W.; Cockerill, S.; Gohil, K.; Parry, N.; Robinson, E.; Randall, R.; Yeates, C.; Snowden, W.; Walters, A. Bioorg. Med. Chem. Lett. 2001, 11, 1993.
33. [33]
  Sanchez-Martinez, C.; Shih, C.; Zhu, G. X.; Li, T. C.; Brooks, H. B.; Patel, B. K.; Schultz, R. M.; DeHahn, T. B.; Spencer, C. D.; Watkins, S. A.; Ogg, C. A.; Considine, E.; Dempsey, J. A.; Zhang, F. M. Bioorg. Med. Chem. Lett. 2003, 13, 3841.
34. [34]
35. [35]
  Davis, P. D.; Bit, R. A.; Hurst, S. A. Tetrahedron Lett. 1990, 31, 2353.
36. [36]
  Haddach, A. A.; Kelleman, A.; Deaton-Rewolinski, M. V. Tetrahedron Lett. 2002, 43, 399.
37. [37]
  Joyce, R. P.; Gainor, J. A.; Weinreb, S. M. J. Org. Chem. 1987, 52, 1177.
38. [38]
  Julia, M.; Tchernoff, G. Bull. Soc. Chim. Fr. 1960, 741.
39. [39]
  Bocchi, V.; Casnati, G.; Dossena, A.; Villani, F. Synthesis 1976, 414.
40. [40]
  Lakatosh, S. A.; Balzarini, J.; Andrei, G.; Snoeck, R.; Lakatosh, A.; De Clercq, E.; Preobrazhenskaya, M. N. J. Antibiot. 2002, 55, 768.
1. [1]
  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
2. [2]
  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
3. [3]
  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
4. [4]
  Ping Song , Nan Zhang , Jie Wang , Rui Yan , Zhiqiang Wang , Yingxue Jin . Experimental Teaching Design on Synthesis and Antitumor Activity Study of Cu-Pyropheophorbide-a Methyl Ester. University Chemistry, 2024, 39(6): 278-286. doi: 10.3866/PKU.DXHX202310087
5. [5]
  Zhilian Liu , Wengui Wang , Hongxiao Yang , Yu Cui , Shoufeng Wang . Ideological and Political Education Design for the Synthesis of Irinotecan Drug Intermediate 7-Ethyl Camptothecin. University Chemistry, 2024, 39(2): 89-93. doi: 10.3866/PKU.DXHX202306012
6. [6]
  Jingjing QING , Fan HE , Zhihui LIU , Shuaipeng HOU , Ya LIU , Yifan JIANG , Mengting TAN , Lifang HE , Fuxing ZHANG , Xiaoming ZHU . Synthesis, structure, and anticancer activity of two complexes of dimethylglyoxime organotin. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1301-1308. doi: 10.11862/CJIC.20240003
7. [7]
  Xiaofeng Xia , Jielian Zhu . Innovative Comprehensive Experimental Design: Synthesis of 6-Fluoro-N-benzoyl Tetrahydroquinoline. University Chemistry, 2024, 39(10): 344-352. doi: 10.12461/PKU.DXHX202405063
8. [8]
  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
9. [9]
  Hong RAO , Yang HU , Yicong MA , Chunxin LÜ , Wei ZHONG , Lihua DU . Synthesis and in vitro anticancer activity of phenanthroline-functionalized nitrogen heterocyclic carbene homo- and heterobimetallic silver/gold complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2429-2437. doi: 10.11862/CJIC.20240275
10. [10]
  Linjie ZHU , Xufeng LIU . Synthesis, characterization and electrocatalytic hydrogen evolution of two di-iron complexes containing a phosphine ligand with a pendant amine. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 939-947. doi: 10.11862/CJIC.20240416
11. [11]
  Jiahao Zeng , Hui Chao . 诱导程序性细胞死亡的金属抗肿瘤药物研究. University Chemistry, 2025, 40(6): 145-159. doi: 10.12461/PKU.DXHX202406019
12. [12]
  Wei Zhong , Dan Zheng , Yuanxin Ou , Aiyun Meng , Yaorong Su . K原子掺杂高度面间结晶的g-C₃N₄光催化剂及其高效H₂O₂光合成. Acta Physico-Chimica Sinica, 2024, 40(11): 2406005-. doi: 10.3866/PKU.WHXB202406005
13. [13]
  Guoqiang Chen , Zixuan Zheng , Wei Zhong , Guohong Wang , Xinhe Wu . 熔融中间体运输导向合成富氨基g-C₃N₄纳米片用于高效光催化产H₂O₂. Acta Physico-Chimica Sinica, 2024, 40(11): 2406021-. doi: 10.3866/PKU.WHXB202406021
14. [14]
  Jianyu Qin , Yuejiao An , Yanfeng Zhang . In Situ Assembled ZnWO₄/g-C₃N₄ S-Scheme Heterojunction with Nitrogen Defect for CO₂ Photoreduction. Acta Physico-Chimica Sinica, 2024, 40(12): 2408002-. doi: 10.3866/PKU.WHXB202408002
15. [15]
  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
16. [16]
  Xi YANG , Chunxiang CHANG , Yingpeng XIE , Yang LI , Yuhui CHEN , Borao WANG , Ludong YI , Zhonghao HAN . Co-catalyst Ni₃N supported Al-doped SrTiO₃: Synthesis and application to hydrogen evolution from photocatalytic water splitting. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 440-452. doi: 10.11862/CJIC.20240371
17. [17]
  Chao Liu , Huan Yu , Jiaming Li , Xi Yu , Zhuangzhi Yu , Yuxi Song , Feng Zhang , Qinfang Zhang , Zhigang Zou . Facile synthesis of hierarchical Ti₃C₂/Bi₁₂O₁₇Br₂ Schottky heterojunction with photothermal effect for solar-driven antibiotics photodegradation. Acta Physico-Chimica Sinica, 2025, 41(7): 100075-. doi: 10.1016/j.actphy.2025.100075
18. [18]
  Minna Ma , Yujin Ouyang , Yuan Wu , Mingwei Yuan , Lijuan Yang . Green Synthesis of Medical Chemiluminescence Reagents by Photocatalytic Oxidation. University Chemistry, 2024, 39(5): 134-143. doi: 10.3866/PKU.DXHX202310093
19. [19]
  Qingying Gao , Tao Luo , Jianyuan Su , Chaofan Yu , Jiazhu Li , Bingfei Yan , Wenzuo Li , Zhen Zhang , Yi Liu . Refinement and Expansion of the Classic Cinnamic Acid Synthesis Experiment. University Chemistry, 2024, 39(5): 243-250. doi: 10.3866/PKU.DXHX202311074
20. [20]
  Wenjun Zheng . Application in Inorganic Synthesis of Ionic Liquids. University Chemistry, 2024, 39(8): 163-168. doi: 10.3866/PKU.DXHX202401020

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(928)
HTML views(108)

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

Synthesis and Cytotoxicity of N12-Ethyl Substituted Indolocarbazole Derivatives

Metrics

通讯作者: 陈斌, bchen63@163.com

Synthesis and Cytotoxicity of N₁₂-Ethyl Substituted Indolocarbazole Derivatives