Development of 1-Amino-4-(phenylamino)anthraquinone-2-sulfonate Sodium Derivatives as a New Class of Inhibitors of RANKL-Induced Osteoclastogenesis

Chia Chung Lee, Chun Liang Chen, Fei Lan Liu, Chung Yu Chiou, Tsung Chih Chen, Cheng Chi Wu, Wei Hsin Sun, Deh Ming Chang, Hsu Shan Huang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A series of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium derivatives was synthesized and evaluated for osteoclast inhibition using a TRAP-staining assay. Among them, two compounds, LCCY-13 and LCCY-15, dose-dependently suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Moreover, the cytotoxicity assay on RAW264.7 cells suggested that the inhibition of osteoclastic bone resorption by these compounds was not a result of their cytotoxicity. Further, the inhibitory activities of compounds LCCY-13 and LCCY-15 were further confirmed by including specific inhibition of NFATc1 expression levels in nuclei using an immunofluorescent analysis. In addition, LCCY-13 and LCCY-15 also significantly attenuated the bone resorption activity of osteoclasts according to a pit formation assay. Thus, a new class of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium compounds might be considered as an essential lead structure for the further development of anti-resorptive agents.

Original languageEnglish
Pages (from-to)342-355
Number of pages14
JournalArchiv der Pharmazie
Volume349
Issue number5
DOIs
Publication statusPublished - May 1 2016

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Keywords

  • Anthraquinone derivatives
  • Osteoclastogenesis
  • RANKL
  • TRAP-staining assay

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmaceutical Science

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