Structure-based design, synthesis and evaluation of novel anthra[1,2-d]imidazole-6,11-dione derivatives as telomerase inhibitors and potential for cancer polypharmacology

被引：38

作者：

Chen, Chun-Liang ^{[1
]}

Chang, Deh-Ming ^{[1
,3
]}

Chen, Tsung-Chih ^{[1
]}

Lee, Chia-Chung ^{[1
]}

Hsieh, Hsi-Hsien ^{[5
]}

Huang, Fong-Chun ^{[5
]}

Huang, Kuo-Feng ^{[6
]}

Guh, Jih-Hwa ^{[7
]}

Lin, Jing-Jer ^{[5
,8
]}

Huang, Hsu-Shan ^{[1
,2
,4
]}

机构：

[1] Natl Def Med Ctr, Grad Inst Life Sci, Taipei 114, Taiwan

[2] Natl Def Med Ctr, Sch Pharm, Taipei 114, Taiwan

[3] Natl Def Med Ctr, Triserv Gen Hosp, Taipei 114, Taiwan

[4] Natl Def Med Ctr, Triserv Gen Hosp, Dept Pharm Practice, Taipei 114, Taiwan

[5] Natl Yang Ming Univ, Inst Biopharmaceut Sci, Taipei 112, Taiwan

[6] Chi Mei Med Ctr, Tainan 710, Taiwan

[7] Natl Taiwan Univ, Coll Med, Sch Pharm, Taipei 100, Taiwan

[8] Natl Taiwan Univ, Coll Med, Inst Biochem & Mol Biol, Taipei 100, Taiwan

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 60卷

关键词：

Telomerase; Imidazole-fused anthraquinones; TRAP assay; SEAP assay; Polypharmacology; RAPID COLORIMETRIC ASSAY; G-QUADRUPLEX; CYTOTOXICITY; TARGETS; SURVIVAL; GROWTH; SERIES; CELLS;

D O I：

10.1016/j.ejmech.2012.11.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of anthra[1,2-d]imidazole-6,11-dione derivatives were synthesized and evaluated for telomerase inhibition, hTERT expression and suppression of cancer cell growth in vitro. All of the compounds tested, except for compounds 4, 7, 16, 24, 27 and 28 were selected by the NCI screening system. Among them, compounds 16, 39, and 40 repressed hTERT expression without greatly affecting cell growth, suggesting for the selectivity toward hTERT expression. Taken together, our findings indicated that the analysis of cytotoxicity and telomerase inhibition might provide information applicable for further developing potential telomerase and polypharmacological targeting strategy. Crown Copyright (C) 2012 Published by Elsevier Masson SAS. All rights reserved.

引用

页码：29 / 41

页数：13

共 33 条

[1] HUMAN TELOMERES CONTAIN AT LEAST 3 TYPES OF G-RICH REPEAT DISTRIBUTED NON-RANDOMLY [J].

ALLSHIRE, RC ;

DEMPSTER, M ;

HASTIE, ND .

NUCLEIC ACIDS RESEARCH, 1989, 17 (12) :4611-4627

[2] The nature of telomere fusion and a definition of the critical telomere length in human cells [J].

Capper, Rebecca ;

Britt-Compton, Bethan ;

Tankimanova, Maira ;

Rowson, Jan ;

Letsolo, Boitelo ;

Man, Stephen ;

Haughton, Michele ;

Baird, Duncan M. .

GENES & DEVELOPMENT, 2007, 21 (19) :2495-2508

[3] Beginning to understand the end of the chromosome [J].

Cech, TR .

CELL, 2004, 116 (02) :273-279

[4] An experimental and computational analysis on the differential role of the positional isomers of symmetric bis-2-(pyridyl)-1H-benzimidazoles as DNA binding agents [J].

Chaudhuri, Padmaparna ;

Ganguly, Bishwajit ;

Bhattacharya, Santanu .

JOURNAL OF ORGANIC CHEMISTRY, 2007, 72 (06) :1912-1923

[5] Mammalian telomeres and telomerase [J].

Collins, K .

CURRENT OPINION IN CELL BIOLOGY, 2000, 12 (03) :378-383

[6] Telomerase in the human organism [J].

Collins, K ;

Mitchell, JR .

ONCOGENE, 2002, 21 (04) :564-579

[7]

CULLEN BR, 1992, METHOD ENZYMOL, V216, P362

[8] Targeting telomeres and telomerase [J].

De Cian, Anne ;

Lacroix, Laurent ;

Douarre, Celine ;

Temime-Smaali, Nassima ;

Trentesaux, Chantal ;

Riou, Jean-Francois ;

Mergny, Jean-Louis .

BIOCHIMIE, 2008, 90 (01) :131-155

[9] RAPID COLORIMETRIC ASSAY FOR CELL-GROWTH AND SURVIVAL - MODIFICATIONS TO THE TETRAZOLIUM DYE PROCEDURE GIVING IMPROVED SENSITIVITY AND RELIABILITY [J].

DENIZOT, F ;

LANG, R .

JOURNAL OF IMMUNOLOGICAL METHODS, 1986, 89 (02) :271-277

[10]

Gomez D, 2002, CANCER RES, V62, P3365

← 1 2 3 4 →