Synthesis of 4β-triazole-podophyllotoxin derivatives by azide-alkyne cycloaddition and biological evaluation as potential antitumor agents

被引：38

作者：

Chen, Hong ^{[1
,4
]}

Zuo, Song ^{[1
,2
]}

Wang, Xiaochen ^{[3
]}

Tang, Xiaowei ^{[1
]}

Zhao, Ming ^{[1
]}

Lu, Yanling ^{[1
]}

Chen, Liting ^{[1
]}

Liu, Jing ^{[1
]}

Liu, Yongfeng ^{[1
]}

Liu, Dailin ^{[1
]}

Zhang, Shi ^{[1
]}

Li, Tan ^{[1
]}

机构：

[1] Chinese Peoples Armed Police Force, Coll Med, Pharmacognosy Div, Tianjin 300162, Peoples R China

[2] Chinese Peoples Armed Police Force Hosp Sichuan, Gen Unit, Chengdu Branch, Chengdu 600041, Peoples R China

[3] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA

[4] Tianjin Key Lab Biomarkers Occupat & Environm Haz, Tianjin 300162, Peoples R China

来源：

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

基金：

中国国家自然科学基金;

关键词：

Podophyllotoxin; Triazole; 1,3-Dipolar cycloaddition; Antitumor; DNA TOPOISOMERASE-II; CLICK CHEMISTRY; 1,2,3-TRIAZOLES; INHIBITORS; PODOPHYLLOTOXINS;

D O I：

10.1016/j.ejmech.2011.07.024

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A representative synthetic process of derivatizing the natural product podophyllotoxin utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is described including molecular design, reaction optimization and X-ray structure confirmation. Evaluation of cytotoxicity against human cancer cell lines (Hela, K562 and K562/A02) using MTT assay proves that these triazole derivatives have good antitumor activities. High activities toward the drug resistant K562/A02 cell line reveal promising future for these derivatives. The rarely prepared 1,5-disubstituted triazole isomers, which would be omitted by the "click chemistry", were found to have superior cytotoxicities to that of the 1,4-disubstituted isomers. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：4709 / 4714

页数：6

共 23 条

[1] Studies on novel 4β-[(4-substituted)-1,2,3-triazol-1-yl] podophyllotoxins as potential anticancer agents [J].

Bhat, Bilal A. ;

Reddy, P. Bhaskar ;

Agrawal, Satyam Kumar ;

Saxena, A. K. ;

Kumar, H. M. Sampath ;

Qazi, G. N. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2008, 43 (10) :2067-2072

[2] 'Click' chemistry in polymer and material science: An update [J].

Binder, Wolfgang H. ;

Sachsenhofer, Robert .

MACROMOLECULAR RAPID COMMUNICATIONS, 2008, 29 (12-13) :952-981

[3] Ruthenium-catalyzed azide-alkyne cycloaddition: Scope and mechanism [J].

Boren, Brant C. ;

Narayan, Sridhar ;

Rasmussen, Lars K. ;

Zhang, Li ;

Zhao, Haitao ;

Lin, Zhenyang ;

Jia, Guochen ;

Fokin, Valery V. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (28) :8923-8930

[4]

Cao CN, 1999, CHINESE CHEM LETT, V10, P1003

[5] Polytriazoles as copper(I)-stabilizing ligands in catalysis [J].

Chan, TR ;

Hilgraf, R ;

Sharpless, KB ;

Fokin, VV .

ORGANIC LETTERS, 2004, 6 (17) :2853-2855

[6] Postsynthetic DNA Modification through the Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction [J].

Gramlich, Philipp M. E. ;

Wirges, Christian T. ;

Manetto, Antonio ;

Carell, Thomas .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2008, 47 (44) :8350-8358

[7] Click chemistry, a powerful tool for pharmaceutical sciences [J].

Hein, Christopher D. ;

Liu, Xin-Ming ;

Wang, Dong .

PHARMACEUTICAL RESEARCH, 2008, 25 (10) :2216-2230

[8]

Jardine I., 1980, ANTICANCER AGENTS BA, P319

[9] Spirostanol and furostanol glycosides from the fresh tubers of Polianthes tuberosa [J].

Jin, JM ;

Zhang, YJ ;

Yang, CR .

JOURNAL OF NATURAL PRODUCTS, 2004, 67 (01) :5-9

[10]

Krivopalov V.P., 2005, RUSS CHEM REV+, V74, P339, DOI DOI 10.1070/RC2005V074N04ABEH000893

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