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Synthesis and Anticancer Activity of 4β-Triazole-podophyllotoxin Glycosides |
| Cheng-Ting Zi1,2, 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 |
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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.
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| Keywords
Podophyllotoxin
4β-Triazole-podophyllotoxin
Glycosides
Click reaction
Anticancer
Synthesis
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| Fund:This work was financially supported by the Fund of State Key Laboratory of Phytochemistry and Plant Resource in West China(P2010-KF07). |
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Issue Date: 11 February 2018
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