Citation: Zhou Changjian, Xie Jianwei, Zhang Jie, Dai Bin. Study on the Synthesis and Anti-tumor Activities of Rhein-Amino Acid Conjugates[J]. Chinese Journal of Organic Chemistry, ;2017, 37(1): 122-132. doi: 10.6023/cjoc201607020 shu

Study on the Synthesis and Anti-tumor Activities of Rhein-Amino Acid Conjugates

Zhou Changjian ^a ,
Xie Jianwei ^a,*,, ,
Zhang Jie ^a,*,, ,
Dai Bin ^a

a.
School of Chemistry and Chemical Engineering and Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, Shihezi 832003

Corresponding author: Xie Jianwei, cesxjw@foxmail.com Zhang Jie, zhangjie-xj@163.com
Received Date: 12 July 2016
Revised Date: 20 August 2016

Figures(3)

20 novel rhein-amino acid conjugates were designed and synthesized from the rhein via esterification, etherification, hydrolysis, condensation and salification. Their structures were confirmed by ¹H NMR, ¹³C NMR and HRMS. All the target compounds were tested for cytotoxic activity against five cancer cell lines including Hela, MCF-7, HepG2, KB and HEK293T by methyl thiazolyl tetrazolium (MTT) method in vitro. The results showed that sodium (4, 5-bis (benzyloxy)-9, 10-dioxo-9, 10-dihydroanthracene-2-carbonyl) leucinate (6eb) demonstrated moderate cytotoxic activities (IC₅₀ < 50 µmol•L^-1). The fluorescence of compounds sodium (4, 5-dibutoxy-9, 10-dioxo-9, 10-dihydroanthracene-2-carbonyl) leucinate (6db) and 6eb could be both quenched by DNA. It was speculated that compound 6db interacted with DNA by the static attraction or was partially embedded into DNA.
- rhein,
- amino acid,
- antitumor activity,
- structure-activity relationships
1. [1]
  Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D. M.; Forman, D.; Bray, F. Int. J. Cancer 2015, 136, E359. doi: 10.1002/ijc.29210
2. [2]
  Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2007, 70, 461. doi: 10.1021/np068054v
3. [3]
  Liu, X.; Cheng, J.; Zheng, X. C.; Chen, Y. G.; Wu, C.; Li, B.; Fu, J. F.; Cao, H. W.; Lu, Y. L.; Li, J.; Zheng, J.; Zhou, H. Int. Immunopharmacol. 2009, 9, 1021. doi: 10.1016/j.intimp.2009.03.023
4. [4]
  Chung, J. G.; Tsou, M. F.; Wang, H. H.; Lo, H. H.; Hsieh, S. E.; Yen, Y. S.; Wu, L. T.; Chang, S. H.; Ho, C. C.; Hung, C. F. J. Appl. Toxicol. 1998, 18, 117. doi: 10.1002/(ISSN)1099-1263
5. [5]
  Hao, K.; Qi, Q.; Wan, P.; Zhang, J. W.; Hao, H. P.; Liang, Y.; Xie, L.; Wang, G. J.; Sun, J. G. Basic Clin. Pharmacol. Toxicol. 2014, 114, 160. doi: 10.1111/bcpt.12148
6. [6]
  Yu, L.; Xiang, H.; Fan, J. W.; Wang, D. C.; Yang, F.; Guo, N.; Jin, Q.; Deng, X. M. J. Biotechnol. 2008, 135, 304.
7. [7]
  Gao, Q.; Qin, W. S.; Jia, Z. H.; Zheng, J. M.; Zeng, C. H.; Li, L. S.; Liu, Z. H. Planta Med. 2010, 76, 27. doi: 10.1055/s-0029-1185948
8. [8]
  Peng, L. L.; Yang, J. Y.; Ning, C.; Zhang, J.; Xiao, X. C.; He, D.; Wang, X. Y.; Li, Z. P.; Fu, S. S.; Ning, J. P. Biol. Pharm. Bull. 2012, 35, 1676. doi: 10.1248/bpb.b12-00107
9. [9]
  Yadav, A.; Bhardwaj, R.; Sharma, R. A. Res. J. Med. Plant 2013, 7, 150. doi: 10.3923/rjmp.2013.150.157
10. [10]
  Ip, S. W.; Weng, Y. S.; Lin, S. Y.; Yang, M. D.; Tang, N. Y.; Su, C. C.; Chung, J. G. Anticancer Res. 2007, 27, 379.
11. [11]
  Fernand, V. E.; Losso, J. N.; Truax, R. E.; Villar, E. E.; Bwambok, D. K.; Fakayode, S. O.; Lowry, M.; Warner, I. M. Chem. Biol. Interact. 2011, 192, 220. doi: 10.1016/j.cbi.2011.03.013
12. [12]
  Badria, F. A.; Ibrahim A. S. Drug Discoveries Ther. 2013, 7, 84.
13. [13]
  Wang, Q.; Zhang, N. N.; Li, H. Y.; Jiang, M.; Gao, J.; Bai, G. Acta Pharm. Sin. 2012, 47, 1618 (in Chinese).
14. [14]
  Hsia, T. C.; Yang, J. S.; Chen, G. W.; Chiu, T. H.; Lu, H. F.; Yang, M. D.; Yu, F. S.; Liu, K. C.; Lai, K. C.; Lin, C. C.; Chung, J. G. Anticancer Res. 2009, 29, 309.
15. [15]
  Chang, C. Y.; Chan, H. L.; Lin, H. Y.; Way, T. D.; Kao, M. C.; Song, M. Z.; Lin, Y. J.; Lin, C. W. J. Evidence-Based Complementary Alterna. Med. 2012, 45, 1052
16. [16]
  Lai, W. W.; Yang, J. S.; Lai, K. C.; Kuo, C. L.; Hsu, C. K.; Wang, C. K.; Chang, C. Y.; Lin, J. J.; Tang, N. Y.; Chen, P. Y.; Huang, W. W.; Chung, J. G. In Vivo 2009, 23, 309.
17. [17]
  Gan, Y.; He, L. H.; Zhang, Y. H.; Wang, J. H.; Zhao, J. Chin. J. Org. Chem. 2014, 34, 589 (in Chinese). doi: 10.6023/cjoc201309010
18. [18]
  Marković, V.; Debeljak, N.; Stanojković, T.; Kolundzija, B.; Sladić, D.; Vujcić, M.; Janović, B.; Tanić, N.; Perović, M.; Tesić, V.; Antić, J.; Joksović, M. D. Eur. J. Med. Chem. 2015, 89, 401. doi: 10.1016/j.ejmech.2014.10.055
19. [19]
  Igarashi, Y.; Trujillo, M. E.; Martínez-Molina, E.; Yanase, S.; Miyanaga, S.; Obata, T.; Sakurai, H.; Saiki, I.; Fujita, T.; Furumai, T. Bioorg. Med. Chem. Lett. 2007, 17, 3702. doi: 10.1016/j.bmcl.2007.04.039
20. [20]
  Barthel, B. L.; Mooz, E. L.; Wiener, L. E.; Koch, G. G.; Koch, T. H. J. Med. Chem. 2016, 59, 2205. doi: 10.1021/acs.jmedchem.5b01956
21. [21]
  Zhu, X.; Ye, X.; Song, L.; Luo, Y.; Tang, Q.; Jin, Y.; Li, X. Med. Chem. Res. 2013, 22, 2228. doi: 10.1007/s00044-012-0215-7
22. [22]
  Yuan, Y.-F.; Hu, X.-Y.; He, Y.; Deng, J.-G. Nat. Prod. Commun. 2012, 7, 207.
23. [23]
  Viayna, E.; Sola, I.; Bartolini, M.; Simone, A. D.; Tapia-Rojas, C.; Serrano, F. G.; Sabaté, R.; Juárez-Jiménez, J.; Pérez, B.; Luque, F. J.; Andrisano, V.; Clos, M. V.; Inestrosa, N. C.; Muñoz-Torrero, D. J. Med. Chem. 2014, 57, 2549. doi: 10.1021/jm401824w
24. [24]
  Li, S.-Y.; Jiang, N.; Xie, S.-S.; Wang, X.-B.; Kong, L.-Y. Org. Biomol. Chem. 2014, 12, 801-814. doi: 10.1039/C3OB42010H
25. [25]
  Yao, G.-Y.; Ye, M.-Y.; Huang, R.-Z.; Li, Y.-J.; Pan, Y.-M.; Xu, Q.; Liao, Z.-X.; Wang, H.-S. Bioorg. Med. Chem. Lett. 2014, 24, 501. doi: 10.1016/j.bmcl.2013.12.030
26. [26]
  Liang Y.-K.; Yue, Z.-Z.; Li, J.-X.; Tan, C.; Miao, Z.-H.; Tan, W.-F.; Yang, C.-H. Eur. J. Med. Chem. 2014, 84, 505. doi: 10.1016/j.ejmech.2014.07.047
27. [27]
  Sirajuddin, M.; Ali, S.; Badshah, A. J. Photochem. Photobiol., B 2013, 124, 1. doi: 10.1016/j.jphotobiol.2013.03.013
1. [1]
  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
2. [2]
  Runjie Li , Hang Liu , Xisheng Wang , Wanqun Zhang , Wanqun Hu , Kaiping Yang , Qiang Zhou , Si Liu , Pingping Zhu , Wei Shao . 氨基酸的衍生及手性气相色谱分离创新实验. University Chemistry, 2025, 40(6): 286-295. doi: 10.12461/PKU.DXHX202407059
3. [3]
  Hong CAI , Jiewen WU , Jingyun LI , Lixian CHEN , Siqi XIAO , Dan LI . Synthesis of a zinc-cobalt bimetallic adenine metal-organic framework for the recognition of sulfur-containing amino acids. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 114-122. doi: 10.11862/CJIC.20240382
4. [4]
  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
5. [5]
  Fa Wang , Yu Chen , Hui Chao . Ruthenium(II) Complexes as Photoactivated Chemo-Prodrugs for Hypoxic Tumor Therapy. University Chemistry, 2025, 40(7): 200-212. doi: 10.12461/PKU.DXHX202410024
6. [6]
  Xuejie Wang , Guoqing Cui , Congkai Wang , Yang Yang , Guiyuan Jiang , Chunming Xu . 碳基催化剂催化有机液体氢载体脱氢研究进展. Acta Physico-Chimica Sinica, 2025, 41(5): 100044-. doi: 10.1016/j.actphy.2024.100044
7. [7]
  Ruiying WANG , Hui WANG , Fenglan CHAI , Zhinan ZUO , Benlai WU . Three-dimensional homochiral Eu(Ⅲ) coordination polymer and its amino acid configuration recognition. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 877-884. doi: 10.11862/CJIC.20250052
8. [8]
  Jian Li , Yu Zhang , Rongrong Yan , Kaiyuan Sun , Xiaoqing Liu , Zishang Liang , Yinan Jiao , Hui Bu , Xin Chen , Jinjin Zhao , Jianlin Shi . 高效靶向示踪钙钛矿纳米系统光电增效抗肿瘤. Acta Physico-Chimica Sinica, 2025, 41(5): 100042-. doi: 10.1016/j.actphy.2024.100042
9. [9]
  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
10. [10]
  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
11. [11]
  Lanjun Cheng , Xinyuan Wang , Jie An , Xiang Wu , Chengfeng Zhu , Yanming Fu , Yougui Li . Improvement of the Resolution Experiment of Racemic Tartaric Acid. University Chemistry, 2025, 40(7): 277-285. doi: 10.12461/PKU.DXHX202408010
12. [12]
  Meijin Li , Xirong Fu , Xue Zheng , Yuhan Liu , Bao Li . The Marvel of NAD⁺: Nicotinamide Adenine Dinucleotide. University Chemistry, 2024, 39(9): 35-39. doi: 10.12461/PKU.DXHX202401027
13. [13]
  Keying Qu , Jie Li , Ziqiu Lai , Kai Chen . Unveiling the Mystery of Chirality from Tartaric Acid. University Chemistry, 2024, 39(9): 369-378. doi: 10.12461/PKU.DXHX202310091
14. [14]
  Ran Yu , Chen Hu , Ruili Guo , Ruonan Liu , Lixing Xia , Cenyu Yang , Jianglan Shui . 杂多酸H₃PW₁₂O₄₀高效催化MgH₂储氢. Acta Physico-Chimica Sinica, 2025, 41(1): 2308032-. doi: 10.3866/PKU.WHXB202308032
15. [15]
  Zijian Zhao , Yanxin Shi , Shicheng Li , Wenhong Ruan , Fang Zhu , Jijun Jiang . A New Exploration of the Preparation of Polyacrylic Acid by Free Radical Polymerization Based on the Concept of Green Chemistry. University Chemistry, 2024, 39(5): 315-324. doi: 10.3866/PKU.DXHX202311094
16. [16]
  Jiahe LIU , Gan TANG , Kai CHEN , Mingda ZHANG . Effect of low-temperature electrolyte additives on low-temperature performance of lithium cobaltate batteries. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 719-728. doi: 10.11862/CJIC.20250023
17. [17]
  Junke LIU , Kungui ZHENG , Wenjing SUN , Gaoyang BAI , Guodong BAI , Zuwei YIN , Yao ZHOU , Juntao LI . Preparation of modified high-nickel layered cathode with LiAlO₂/cyclopolyacrylonitrile dual-functional coating. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1461-1473. doi: 10.11862/CJIC.20240189
18. [18]
  Jizhou Liu , Chenbin Ai , Chenrui Hu , Bei Cheng , Jianjun Zhang . 六氯锡酸铵促进钙钛矿太阳能电池界面电子转移及其飞秒瞬态吸收光谱研究. Acta Physico-Chimica Sinica, 2024, 40(11): 2402006-. doi: 10.3866/PKU.WHXB202402006
19. [19]
  Ke Li , Chuang Liu , Jingping Li , Guohong Wang , Kai Wang . 钛酸铋/氮化碳无机有机复合S型异质结纯水光催化产过氧化氢. Acta Physico-Chimica Sinica, 2024, 40(11): 2403009-. doi: 10.3866/PKU.WHXB202403009
20. [20]
  Yukun Chang , Haoqin Huang , Baolei Wang . Preparation of Trans-Cinnamic Acid via “One-Pot” Protocol of Aldol Condensation-Hydrolysis Reaction: Recommending an Improved Organic Synthesis Experiment. University Chemistry, 2024, 39(4): 322-328. doi: 10.3866/PKU.DXHX202309095

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(1422)
HTML views(145)

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