Synthesis and antitumor activity of novel per-butyrylated glycosides of podophyllotoxin and its derivatives.
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.
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.
Cheng-Ting
CT
Zi
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
Dan
D
Yang
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
Fa-Wu
FW
Dong
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
Gen-Tao
GT
Li
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
Yan
Y
Li
Key Laboratory of Medicinal Chemistry for Natural Resource, Yunnan University, Kunming 650091, China.
Zhong-Tao
ZT
Ding
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
Jun
J
Zhou
Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, ON P7B 5E1, Canada. Electronic address: zjiang@lakeheadu.ca.
Zi-Hua
ZH
Jiang
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.
Jiang-Miao
JM
Hu
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D006027:Glycosides / Q000138:chemical synthesis*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D011034:Podophyllotoxin / Q000138:chemical synthesis*
D000970:Antineoplastic Agents; D006027:Glycosides; D011034:Podophyllotoxin
4′-Demethylepipodophyllotoxin; Antitumor; Butyrylated glycosides; Cytotoxic; Epipodophyllotoxin; Podophyllotoxin; Synthesis