Synthesis and biological evaluation of derivatives of 4-deoxypodophyllotoxin as antitumor agents

被引：33

作者：

Jin, Yan ^{[3
]}

Liu, Jie ^{[3
]}

Huang, Wen-Ting ^{[1
,2
]}

Chen, Shi-Wu ^{[1
,2
]}

Hui, Ling ^{[4
]}

机构：

[1] Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China

[2] Lanzhou Univ, Key Lab Preclin Study New Drugs Gansu Prov, Lanzhou 730000, Peoples R China

[3] Qingdao Univ Sci & Technol, Coll Chem Engn, Qingdao 266042, Peoples R China

[4] Lanzhou Mil Command, Gen Hosp, Ctr Med Expt, Key Lab Stem Cells & Gene Drug Gansu Prov, Lanzhou 730050, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 09期

关键词：

Podophyllotoxin; 4-Deoxypodophyllotoxin; Piperazine; Antitumor activity; SPIN-LABELED DERIVATIVES; CELL-CYCLE ARREST; PODOPHYLLOTOXIN DERIVATIVES; CYTOTOXIC ACTIVITY; DEOXYPODOPHYLLOTOXIN; APOPTOSIS; 4'-DEMETHYL-4-DEOXYPODOPHYLLOTOXIN; 4'-DEMETHYLEPIPODOPHYLLOTOXIN; INDUCTION; PLANTS;

D O I：

10.1016/j.ejmech.2011.06.004

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

In an attempt to generate compounds with superior bioactivity and reduced toxicity, a series of derivatives of deoxypodophyllotoxin were synthesized by reacting 4'-demethyl-4-deoxypodophyllotoxin with substituted piperazines or their amino acid amides. The cytotoxic activity of these compounds against three human cancer cell lines was evaluated. We found that p-nitrophenylpiperazine substitution (Compound 8b) led to an increase in the potency of the compound. Compound 8b exhibited the most potent cytotoxicity against A-549, HeLa and SiHa cells (IC50 values were 0.102, 0.180 and 0.0195 mu M, respectively). In addition, flow cytometric analysis showed that 8b induced cell cycle arrest in the G1 phase accompanied by apoptosis in A-549 cells. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：4056 / 4061

页数：6

共 30 条

[1]

Podophyllotoxin [J].