Semi-Synthesis and Biological Evaluation of 1,2,3-Triazole-Based Podophyllotoxin Congeners as Potent Antitumor Agents Inducing Apoptosis in HepG2 Cells

被引：13

作者：

Chen, Jinying ^{[1
]}

Ma, Liang ^{[1
]}

Zhang, Ronghong ^{[1
]}

Tang, Jie ^{[3
]}

Lai, Huijun ^{[2
]}

Wang, Jun ^{[1
]}

Wang, Guangcheng ^{[1
]}

Xu, Qinyuan ^{[1
]}

Chen, Tao ^{[1
]}

Peng, Fei ^{[1
]}

Qiu, Jingxiang ^{[1
]}

Liang, Xiaolin ^{[1
]}

Cao, Dong ^{[1
]}

Ran, Yan ^{[1
]}

Peng, Aihua ^{[1
]}

Wei, Yuquan ^{[1
]}

Chen, Lijuan ^{[1
]}

机构：

[1] Sichuan Univ, W China Hosp, W China Med Sch, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China

[2] Sichuan Univ, Inst Chem Engn, Chengdu 610041, Sichuan, Peoples R China

[3] Sichuan Univ, W China Sch Pharm, Chengdu 610041, Sichuan, Peoples R China

来源：

ARCHIV DER PHARMAZIE | 2012年 / 345卷 / 12期

关键词：

Antitumor activity; Cell cycle; Docking study; G2; M phase; Podophyllotoxin congeners; TOPOISOMERASE II-ALPHA; CLICK CHEMISTRY; HUMAN DNA; ETOPOSIDE; DERIVATIVES; ANALOGS;

D O I：

10.1002/ardp.201100438

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4 beta-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin congeners were synthesized by employing click chemistry and further evaluated for their antitumor activity by MTT assay. Among them, six congeners (10, 11, 12, 13, 22, and 24) exhibited approximately 100-fold more potent inhibitory activity against four tumor cell lines (HepG2, MKN-45, NCI-H1993, and B16) than etoposide as positive control. Docking studies on binding in the ATPase domain of topoisomerase II revealed perfect docking of four congeners in the active site. Furthermore, the podophyllotoxin congeners 10, 11, 12, and 13 induced cell cycle arrest of HepG2 cells at the G2/M phase in a concentration-dependent manner, assessed by flow cytometric analysis, highlighting that they exert their antitumor activity via HepG2 cell apoptosis.

引用

页码：945 / 956

页数：12

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