Carbamates of 4′-demethyl-4-deoxypodophyllotoxin: Synthesis, cytotoxicity and cell cycle effects

被引：33

作者：

Chen, Shi-Wu ^{[1
]}

Gao, Yuan-Yu ^{[1
]}

Zhou, Ni-Ni ^{[1
]}

Liu, Jie ^{[2
]}

Huang, Wen-Ting ^{[1
]}

Hui, Ling ^{[3
,4
]}

Jin, Yan ^{[2
]}

Jin, Yong-Xin ^{[5
]}

机构：

[1] Lanzhou Univ, Sch Pharm, State Key Lab Appl Organ Chem, Key Lab Preclin Study New Drugs Gansu Prov, Lanzhou 730000, Peoples R China

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

[3] Gen Hosp Lanzhou Mil Command, Ctr Med Expt, Lanzhou 730050, Peoples R China

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

[5] Second Peoples Hosp Gansu Prov, Dept Med, Lanzhou 730000, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 24期

关键词：

Podophyllotoxin; 4-Deoxypodophyllotoxin; Amino acid; Antitumor activity; SPIN-LABELED DERIVATIVES; PODOPHYLLOTOXIN DERIVATIVES; BIOLOGICAL EVALUATION; ANTITUMOR AGENTS; DEOXYPODOPHYLLOTOXIN; PLANTS; PART;

D O I：

10.1016/j.bmcl.2011.10.024

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, 12 carbamates of 4'-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4'-demethyl- 4-deoxypodophyllic)-alpha-amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities against four cell lines (A-549, HeLa, SiHa, and HL-60) compared with either parent DPT or anti-cancer drug VP-16. Furthermore, flow cytometric analysis exhibited that N-(1-oxyl-4'-demethyl-4-deoxypodophyllic)-D-alpha-methine amide (15f) induced cell cycle arrest in the G2/M phase in A-549 cells. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：7355 / 7358

页数：4

共 33 条

[1]

Synthesis and antibacterial studies of binaphthyl-based tripeptoids. Part 1 [J].