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Chinese Journal of Organic Chemistry >

2015 , Vol. 35 >Issue 4: 835 - 842

DOI: https://doi.org/10.6023/cjoc201410013

ARTICLE

Rational Synthesis and Preliminary Anti-cancer Activities of 18β-Glycyrrhetinic Acid Derivatives Containing Pyridinecarboxamide

  • Chen Couxi ,
  • Wei Mengxue ,
  • Li Xueqiang ,
  • Li Tiancai ,
  • Zhou Xuezhang
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  • a School of Chemistry and Chemical Engineering, Ningxia University, Yinchuan 750021;
    b Ningxia Development Center of Natural Products and Medication, Yinchuan 750021;
    c Key Laboratory of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan 750021

Received date: 2014-10-09

  Revised date: 2014-12-07

  Online published: 2014-12-23

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 21462032, 21062014), the University of Science and Technology Research Project in Nignxia Province (No. NGY.2013171) and the Research Starting Funds for Imported Talents, Ningxia University (No. 80020241).

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Abstract

Five novel containing pyridinecarboxamide 18β-glycyrrhetinic acid derivatives have been designed and synthesized following the concept of ‘active structural splice’. In vitro studies demonstrated that all derivatives showed strong anti-cancer activities in thiazolylblue (MTT) assay towards Hela cell lines. They were founded to inhibit the Hela cell lines prolifration and induce apoptosis as the lowest IC50 values was only 0.02 μmol·L-1. Under the same conditions, these showed lower IC50 of cells growth than that of cytarabine. All findings supported further optimization efforts based on 18β-glycyrrhetinic acid as a lead compound to develop potential anti-cancer drug candidates.

Key words： 18β-glycyrrhetinic acid; pyridine; amide; derivative; anti-tumor activity

Cite this article

Chen Couxi , Wei Mengxue , Li Xueqiang , Li Tiancai , Zhou Xuezhang . Rational Synthesis and Preliminary Anti-cancer Activities of 18β-Glycyrrhetinic Acid Derivatives Containing Pyridinecarboxamide[J]. Chinese Journal of Organic Chemistry, 2015 , 35(4) : 835 -842 . DOI: 10.6023/cjoc201410013

References

[1] Schwarz, S.; Siewert, B.; Xavier, N. M.; Jesus, A. R.; Rauter, A. P.; Csuk, R. Eur. J. Med. Chem. 2014, 72, 78.
[2] Wang, J.; Wen, W. H.; Hu, X. L.; Zhu, Y. L. Chin. J. Org. Chem. 2012, 32, 138 (Chinese).
(王军, 文伟河, 胡小丽, 朱玉亮, 有机化学, 2012, 32, 138.)
[3] Schwarz, S.; Lucas, S. D.; Sommerwerk, S.; Csuk, R. Bioorg. Med. Chem. 2014, 22, 3370
[4] Parida, P. K.; Sau, A.; Ghosh, T.; Jana, K.; Biswas, K.; Raha, S.; Misra, A. K. Bioorg. Med. Chem. Lett. 2014, 24, 3865.
[5] Salomatina, O. V.; Markov, A. V.; Logashenko, E. B.; Korchagina, D. V.; Zenkova, M. A.; Salakhutdinov, N. F.; Vlassov, V. V.; Tolstikov, G. A. Bioorg. Med. Chem. 2014, 22, 585.
[6] Csuk, R.; Schwarz, S.; Siewert, B.; Kluge, R.; Ströhl, D. Eur. J. Med. Chem. 2011, 46, 5356.
[7] Hu, J.; Wu Y.; Zhao, C.-Q.; Ju, Y. Chem. J. Chin. Univ. 2010, 31, 1762 (Chinese).
(胡君, 吴洋, 赵长崎, 巨勇, 高等学校化学学报, 2010, 31, 1762.)
[8] Gaware, R.; Khunt, R.; Czollner, L.; Stanetty, C.; Cunha, T. D.; Kratschmar, D. V.; Odermatt, A.; Kosma, P.; Jordis, U.; Claßen- Houben, D. Bioorg. Med. Chem. 2011, 19, 1866.
[9] Liu, Y. Q.; Qian, K. D.; Wang, C.-Y.; Chen, C.-H.; Yang, X. M.; Lee, K.-H. Bioorg. Med. Chem. Lett. 2012, 22, 7530.
[10] Wang, L.-J.; Geng, C.-A.; Ma, Y.-B.; Huang, X-Y.; Luo, J.; Chen, H.; Zhang, X.-M.; Chen, J.-J. Bioorg. Med. Chem. Lett. 2012, 22, 3473.
[11] Gao, Z. B.; Hu, J.; Kang, X.; Xu, C. L.; Ju, Y. Chem. J. Chin. Univ. 2012, 33, 750 (Chinese).
(高振北, 胡君, 康潇, 许传莲, 巨勇, 高等学校化学学报, 2012, 33, 750.)
[12] Lin, K.-W.; Huang, A.-M.; Hour, T.-C.; Yang, S.-C.; Pu, Y.-S.; Lin, C.-N. Bioorg. Med. Chem. 2011, 19, 4274.
[13] Hu, J.; Yu, L. B.; Zhang, M.; Ju, Y. Chin. J. Chem. 2011, 29, 1139.
[14] Liu, L.-J.; Yong, J.-P.; Dai, X. J.; Jia, J.; Wang, X. Z.; Wang, J. W. Chem. J. Chin. Univ. 2006, 27, 1669 (Chinese).
(刘利军, 雍建平, 戴小军, 贾炯, 王西照, 王建武, 高等学校化学学报, 2006, 27, 1669.)
[15] Lallemand, B.; Ouedraogo, M.; Wauthoz, N.; Lamkami, T.; Mathieu, V.; Jabin, I.; Amighi, K.; Kiss, R.; Dubois, J.; Goole, J. J. Pharm. Pharmacol. 2013, 65, 402.
[16] Zhao, K.; Ding, M.; Cao, H.; Cao, Z.-X. J. Pharm. Pharmacol. 2012, 64, 1445.
[17] Kurono, M.; Ishiwata, Y.; Yokochi, S.; Asano, K.; Mitani, T.; Kakigami, T.; Iwata, N.; Isogawa, K.; Baba, Y.; et al. EP 518533, 1992 [Chem. Abstr. 1993, 119, 73029].
[18] Chen, C. X.; Li, X. Q.; Li, T. C.; Zhou, X. Z. Acta Chim. Sinica 2012, 70, 852 (Chinese).
(陈凑喜, 李学强, 李天才, 周学章, 化学学报, 2012, 70, 852.)
[19] Lee, J. S.; Shim, H. S.; Park, Y. K.; Park, S. J.; Shin, J. S.; Yang, W. Y.; Lee, H. D.; Park, W. J.; Chung, Y. H.; Lee, S. W. Bioorg. Med. Chem. Lett. 2002, 12, 2715.
[20] Guo, Z. R.; Dowdy, E. D.; Li, W.-S.; Polniaszek, R.; Delaney, E. Tetrahedron Lett. 2001, 42, 1843.
[21] Faul, M. M.; Ratz, A. M.; Sullivan, K. A.; Trankle, W. G.; Winneroski, L. L. J. Org. Chem. 2001, 66, 5772.
[22] Schiffner, J. A.; Wöste, T. H.; Oestreich, M. Eur. J. Org. Chem. 2010, 174.
[23] Wei, M.-X.; Feng, L.; Li, X,-Q.; Zhou, X.-Z.; Shao, Z.-H. Eur. J. Med. Chem. 2009, 44, 3340.

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