Ring fusion strategy for synthesis and lead optimization of sulfur-substituted anthra[1,2-c[[1,2,5]thiadiazole-6,11-dione derivatives as promising scaffold of antitumor agents

Yu Ru Lee, Tsung Chih Chen, Chia Chung Lee, Chun Liang Chen, Ahmed Atef Ahmed Ali, Alexander Tikhomirov, Jih Hwa Guh, Dah Shyong Yu, Hsu Shan Huang

Research output: Contribution to journalArticle

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Abstract

A series of sulfur-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-diones were synthesized and evaluated using the cell proliferations, apoptosis and NCI-60 cell panel assays. Also, the signaling pathways that account for their activities were investigated. Compounds 2, 3, 4a, 4d, 4f, 4i, 4k, 5b, 5c, 5d, 5f, 5g, 6b, 6c, 6d, 6e, 6g, 7a and 7g were selected by NCI. Among the tested compounds, 6g appeared to be the most active compound of this series that not only induced apoptosis in DU-145 cancer cells but also attenuated the ERK1/2 and p38 signaling pathways. All test compounds exhibited diverse cytostatic and cytotoxic activities that warrant further development as potential anticancer agents.

Original languageEnglish
Pages (from-to)661-676
Number of pages16
JournalEuropean Journal of Medicinal Chemistry
Volume102
DOIs
Publication statusPublished - Sep 18 2015

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Sulfur
Scaffolds
Antineoplastic Agents
Fusion reactions
Apoptosis
Derivatives
Cell proliferation
Cytostatic Agents
Assays
Cells
Cell Proliferation
Neoplasms
anthra(2,1-c)(1,2,5)thiadiazole-6,11-dione

Keywords

  • Anthra[1 2-c][1 2 5]thiadiazole-6 11-dione
  • Apoptosis
  • NCI 60-cell panel assay
  • SRB assay
  • Thiadiazoles

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Ring fusion strategy for synthesis and lead optimization of sulfur-substituted anthra[1,2-c[[1,2,5]thiadiazole-6,11-dione derivatives as promising scaffold of antitumor agents. / Lee, Yu Ru; Chen, Tsung Chih; Lee, Chia Chung; Chen, Chun Liang; Ahmed Ali, Ahmed Atef; Tikhomirov, Alexander; Guh, Jih Hwa; Yu, Dah Shyong; Huang, Hsu Shan.

In: European Journal of Medicinal Chemistry, Vol. 102, 18.09.2015, p. 661-676.

Research output: Contribution to journalArticle

Lee, Yu Ru ; Chen, Tsung Chih ; Lee, Chia Chung ; Chen, Chun Liang ; Ahmed Ali, Ahmed Atef ; Tikhomirov, Alexander ; Guh, Jih Hwa ; Yu, Dah Shyong ; Huang, Hsu Shan. / Ring fusion strategy for synthesis and lead optimization of sulfur-substituted anthra[1,2-c[[1,2,5]thiadiazole-6,11-dione derivatives as promising scaffold of antitumor agents. In: European Journal of Medicinal Chemistry. 2015 ; Vol. 102. pp. 661-676.
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