2. Academic Validation
  3. Synthesis and antitumor activity of novel per-butyrylated glycosides of podophyllotoxin and its derivatives

Synthesis and antitumor activity of novel per-butyrylated glycosides of podophyllotoxin and its derivatives

  • Bioorg Med Chem. 2015 Apr 1;23(7):1437-46. doi: 10.1016/j.bmc.2015.02.021.
Cheng-Ting Zi 1,  Dan Yang 2,  Fa-Wu Dong 2,  Gen-Tao Li 2,  Yan Li 2,  Zhong-Tao Ding 3,  Jun Zhou 2,  Zi-Hua Jiang 4,  Jiang-Miao Hu 5
Affiliations

Affiliations

  • 1 Key Laboratory of Medicinal Chemistry for Natural Resource, Yunnan University, Kunming 650091, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
  • 2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
  • 3 Key Laboratory of Medicinal Chemistry for Natural Resource, Yunnan University, Kunming 650091, China.
  • 4 Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, ON P7B 5E1, Canada. Electronic address: zjiang@lakeheadu.ca.
  • 5 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. Electronic address: hujiangmiao@mail.kib.ac.cn.
PMID: 25744190 DOI: 10.1016/j.bmc.2015.02.021
Abstract

A series of perbutyrylated glycosides of podophyllotoxin and its derivatives were synthesized and evaluated for their antitumor activity in vitro. Most of them exhibit cytotoxic activity against a panel of five human Cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Among the synthesized compounds, epipodophyllotoxin α-d-galactopyranoside 8b, epipodophyllotoxin α-d-arabinopyranoside 8e, and podophyllotoxin β-d-glucopyranoside 11a show the highest potency of Anticancer activity with their IC50 values ranging from 0.14 to 1.69μM. Structure activity relationship analysis indicates that the type of glycosidic linkage, the configuration at C-4 of the podophyllotoxin scaffold, and the substitution at 4'-position (OH vs OCH3) can all have significant effect on the potency of their Anticancer activity. Several compounds are more active than the control drugs Etoposide and Cisplatin, suggesting their potential as Anticancer agents for further development.

Keywords

4′-Demethylepipodophyllotoxin; Antitumor; Butyrylated glycosides; Cytotoxic; Epipodophyllotoxin; Podophyllotoxin; Synthesis.

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