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

Chun Liang Chen, Deh Ming Chang, Tsung Chih Chen, Chia Chung Lee, Hsi Hsien Hsieh, Fong Chun Huang, Kuo Feng Huang, Jih Hwa Guh, Jing Jer Lin, Hsu Shan Huang

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)29-41
Number of pages13
JournalEuropean Journal of Medicinal Chemistry
Volume60
DOIs
Publication statusPublished - Feb 2013
Externally publishedYes

Fingerprint

Polypharmacology
Telomerase
Cell growth
Derivatives
Neoplasms
Cytotoxicity
Growth
Screening
heparinized hydrophilic polymer
imidazole

Keywords

  • Imidazole-fused anthraquinones
  • Polypharmacology
  • SEAP assay
  • Telomerase
  • TRAP assay

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

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. / Chen, Chun Liang; Chang, Deh Ming; Chen, Tsung Chih; Lee, Chia Chung; Hsieh, Hsi Hsien; Huang, Fong Chun; Huang, Kuo Feng; Guh, Jih Hwa; Lin, Jing Jer; Huang, Hsu Shan.

In: European Journal of Medicinal Chemistry, Vol. 60, 02.2013, p. 29-41.

Research output: Contribution to journalArticle

Chen, Chun Liang ; Chang, Deh Ming ; Chen, Tsung Chih ; Lee, Chia Chung ; Hsieh, Hsi Hsien ; Huang, Fong Chun ; Huang, Kuo Feng ; Guh, Jih Hwa ; Lin, Jing Jer ; Huang, Hsu Shan. / 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. In: European Journal of Medicinal Chemistry. 2013 ; Vol. 60. pp. 29-41.
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abstract = "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.",
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AU - Chang, Deh Ming

AU - Chen, Tsung Chih

AU - Lee, Chia Chung

AU - Hsieh, Hsi Hsien

AU - Huang, Fong Chun

AU - Huang, Kuo Feng

AU - Guh, Jih Hwa

AU - Lin, Jing Jer

AU - Huang, Hsu Shan

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