Synthesis and Anticancer Activity of 4β-Triazole-podophyllotoxin Glycosides

doi:10.1007/s13659-015-0057-3

应用天然产物 ›› 2015, Vol. 5 ›› Issue (2): 83-90.DOI: 10.1007/s13659-015-0057-3

• Original article • 上一篇下一篇

Synthesis and Anticancer Activity of 4β-Triazole-podophyllotoxin Glycosides

Cheng-Ting Zi^1,2, Gen-Tao Li¹, Yan Li¹, Jun Zhou¹, Zhong-Tao Ding², Zi-Hua Jiang³, Jiang-Miao Hu¹

1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
2. Key Laboratory of Medicinal Chemistry for Nature Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China;
3. Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, ON P7 B5 E1, Canada

收稿日期:2015-03-02 修回日期:2015-03-22 出版日期:2015-04-24 发布日期:2018-02-11
基金资助:
This work was financially supported by the Fund of State Key Laboratory of Phytochemistry and Plant Resource in West China(P2010-KF07).

Synthesis and Anticancer Activity of 4β-Triazole-podophyllotoxin Glycosides

Cheng-Ting Zi^1,2, Gen-Tao Li¹, Yan Li¹, Jun Zhou¹, Zhong-Tao Ding², Zi-Hua Jiang³, Jiang-Miao Hu¹

1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
2. Key Laboratory of Medicinal Chemistry for Nature Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China;
3. Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, ON P7 B5 E1, Canada

Received:2015-03-02 Revised:2015-03-22 Online:2015-04-24 Published:2018-02-11
Supported by:
This work was financially supported by the Fund of State Key Laboratory of Phytochemistry and Plant Resource in West China(P2010-KF07).

摘要/Abstract

摘要： A series of novel 4β-triazole-podophyllotoxin glycosides were synthesized by utilizing the Click reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines(HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assay shows that most of these compounds show weak cytotoxicity. It was observed that compound 16 shows the highest activity with IC₅₀ values ranging from 2.85 to 7.28 μM, which is more potent than the control drugs etoposide and cisplatin against four of five cancer cell lines tested. Compound 16 is characterized with an α-D-galactosyl residue directly linked to the triazole ring and a 4'-OH group on the E ring of the podophyllotoxin scaffold. HPLC investigation of representative compound indicates that incorporation of a sugar moiety seems to improve the chemical stability of the podophyllotoxin scaffold.

关键词: Podophyllotoxin, 4β-Triazole-podophyllotoxin, Glycosides, Click reaction, Anticancer, Synthesis

Abstract: A series of novel 4β-triazole-podophyllotoxin glycosides were synthesized by utilizing the Click reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines(HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assay shows that most of these compounds show weak cytotoxicity. It was observed that compound 16 shows the highest activity with IC₅₀ values ranging from 2.85 to 7.28 μM, which is more potent than the control drugs etoposide and cisplatin against four of five cancer cell lines tested. Compound 16 is characterized with an α-D-galactosyl residue directly linked to the triazole ring and a 4'-OH group on the E ring of the podophyllotoxin scaffold. HPLC investigation of representative compound indicates that incorporation of a sugar moiety seems to improve the chemical stability of the podophyllotoxin scaffold.

Key words: Podophyllotoxin, 4β-Triazole-podophyllotoxin, Glycosides, Click reaction, Anticancer, Synthesis

Cheng-Ting Zi, Gen-Tao Li, Yan Li, Jun Zhou, Zhong-Tao Ding, Zi-Hua Jiang, Jiang-Miao Hu. Synthesis and Anticancer Activity of 4β-Triazole-podophyllotoxin Glycosides[J]. 应用天然产物, 2015, 5(2): 83-90.

Cheng-Ting Zi, Gen-Tao Li, Yan Li, Jun Zhou, Zhong-Tao Ding, Zi-Hua Jiang, Jiang-Miao Hu. Synthesis and Anticancer Activity of 4β-Triazole-podophyllotoxin Glycosides[J]. Natural Products and Bioprospecting, 2015, 5(2): 83-90.

参考文献

1. M.Á. Castro, J.M. Miguel del Corral, P.A. García, M.V. Rojo, J. de la Iglesia-Vicente, F. Mollinedo, C. Cuevas, A.S. Feliciano, J. Med. Chem. 53, 983-993 (2010)
2. J.L. Hartwell, A.W. Schrecker, J. Am. Chem. Soc. 73, 2909-2916 (1951)
3. I. Jardine, J.M. Cassady, J. Douros, In the anticancer agents based on natural product models (Academic Press, New York, 1980), p. 319
4. B.F. Issell, Cancer Chemother. Pharmacol. 7, 73-80 (1982)
5. T. Terada, K. Fujimoto, M. Nomura, J. Yamashita, K. Wierzba, R. Yamazaki, J. Shibata, Y. Sugimoto, Y. Yamada, T. Kobunai, S. Takeda, Y. Minami, K. Yoshida, H. Yamaguchi, J. Med. Chem. 36, 1689-1699 (1993)
6. Z.Y. Xiao, Y.D. Xiao, J. Feng, A. Golbraikh, A. Tropsha, K.H. Lee, J. Med. Chem. 45, 2294-2309 (2002)
7. R. Tawa, M. Takami, Y. Imakura, K.H. Lee, H. Sakuri, Bioorg. Med. Chem. Lett. 7, 489-494 (1997)
8. P. Thirumurugan, D. Matosiuk, K. Jozwiak, Chem. Rev. 113, 4905-4979 (2013)
9. P.B. Reddy, D.V. Paul, S.K. Agrawal, A.K. Saxena, H.M.S. Kumar, G.N. Qazi, Arch. Pharm. Chem. Life Sci. 341, 126-131 (2008)
10. C.T. Zi, F.Q. Xu, G.T. Li, Y. Li, Z.T. Ding, J. Zhou, Z.H. Jiang, J.M. Hu, Molecules 18, 1420-1430 (2013)
11. V.V. Rostovtsev, L.G. Green, V.V. Fokin, K.B. Sharpless, Angew. Chem. Int. Ed. 41, 2596-2599 (2002)
12. C.W. Tornoe, C. Christensen, M. Meldal, J. Org. Chem. 67, 3057-3064 (2002)
13. B. Mukhopadhyay, Tetrahedron Lett. 47, 4337-4341 (2006)
14. B. Roy, B. Mukhopadhyay, Tetrahedron Lett. 48, 3783-3787 (2007)
15. V.K. Rajput, B. Mukhopadhyay, Tetrahedron Lett. 47, 5939-5941 (2006)
16. P. Simerska, M. Kuzma, D. Monti, S. Riva, M. Mackova, V. Kǐren, J. Mol. Catal. B 39, 128-134 (2006)
17. O. Michel, B.J. Ravoo, Langmuir 24, 12116-12118 (2008)
18. T. Hasegawa, M. Numata, S. Okumura, T. Kimura, K. Sakurai, S. Shinkai, Org. Biomol. Chem. 5, 2404-2412 (2007)
19. L. Cui, J.A. Cohen, K.E. Broaders, T.T. Beaudette, J.M.J. Fré-chet, Bioconjug Chem. 22, 949-957 (2011)
20. A.S. Rowan, N.I. Nicely, N. Cochrane, W.A. Wlassoff, A. Claiborneb, C.J. Hamilton, Org. Biomol. Chem. 7, 4029-4036 (2009)
21. A. Kamal, N. Laxman, G. Ramesh, Bioorg. Med. Chem. Lett. 10, 2059-2062 (2000)
22. X.M. Zhou, Z.Q. Wang, J.Y. Chang, H.X. Chen, K.H. Yung, J. Med. Chem. 34, 3346-3350 (1991)
23. S.W. Chen, Y.H. Wang, Y. Jin, X. Tian, Y.T. Zheng, D.Q. Luo, Y.Q. Tu, Bioorg. Med. Chem. Lett. 17, 2091-2095 (2007)
24. K.J. Doores, B.G. Davis, Org. Biomol. Chem. 6, 2692-2696 (2008)
25. L.J. Reed, H. Muench, Am. J. Hyg. 27, 493-497 (1938)
26. W.J. Gensler, C.D. Gatsonis, J. Org. Chem. 31, 3224-3227 (1966)

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Synthesis and Anticancer Activity of 4β-Triazole-podophyllotoxin Glycosides

Synthesis and Anticancer Activity of 4β-Triazole-podophyllotoxin Glycosides

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