Design, Synthesis, and Cytotoxicity of Perbutyrylated Glycosides of 4β-Triazolopodophyllotoxin Derivatives
Cheng-Ting Zi,
Zhen-Hua Liu,
Gen-Tao Li,
Yan Li,
Jun Zhou,
Zhong-Tao Ding,
Jiang-Miao Hu,
Zi-Hua Jiang
Affiliations
Cheng-Ting Zi
Key Laboratory of Medicinal Chemistry for Nature Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China
Zhen-Hua Liu
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China
Gen-Tao Li
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China
Yan Li
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China
Jun Zhou
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China
Zhong-Tao Ding
Key Laboratory of Medicinal Chemistry for Nature Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China
Jiang-Miao Hu
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China
Zi-Hua Jiang
Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, ON P7B 5E1, Canada
A series of novel perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using the MTT assay shows that some of these glycosylated derivatives have good anticancer activity. Among the synthesized compounds, compound 21a shows the highest activity, with IC50 values ranging from 0.49 to 6.70 μM, which is more potent than the control drugs etoposide and cisplatin. Compound 21a is characterized by a perbutyrylated α-D(+)-galactosyl residue, the absence of an additional linking spacer between the sugar residue and the triazole ring, as well as a 4'-OH group on the E ring of the podophyllotoxin scaffold.
