Modified salicylanilide and 3-phenyl-2 H -benzo[ e ][1,3]oxazine-2,4(3 H)-dione derivatives as novel inhibitors of osteoclast differentiation and bone resorption

Chun Liang Chen, Fei Lan Liu, Chia Chung Lee, Tsung Chih Chen, Ahmed Atef Ahmed Ali, Huey Kang Sytwu, Deh Ming Chang, Hsu Shan Huang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Inhibition of osteoclast formation is a potential strategy to prevent inflammatory bone resorption and to treat bone diseases. In the present work, the purpose was to discover modified salicylanilides and 3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivatives as potential antiosteoclastogenic agents. Their inhibitory effects on RANKL-induced osteoclastogenesis from RAW264.7 cells were evaluated by TRAP stain assay. The most potent compounds, 1d and 5d, suppressed RANKL-induced osteoclast formation and TRAP activity dose-dependently. The cytotoxicity assay on RAW264.7 cells suggested that the inhibition of osteoclastic bone resorption by these compounds did not result from their cytotoxicity. Moreover, both compounds downregulated RANKL-induced NF-κB and NFATc1 in the nucleus, suppressed the expression of osteoclastogenesis-related marker genes during osteoclastogenesis, and prevented osteoclastic bone resorption but did not impair osteoblast differentiation in MC3T3-E1. Therefore, these modified salicylanilides and 3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones could be potential lead compounds for the development of a new class of antiresorptive agents.

Original languageEnglish
Pages (from-to)8072-8085
Number of pages14
JournalJournal of Medicinal Chemistry
Volume57
Issue number19
DOIs
Publication statusPublished - Oct 9 2014

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Salicylanilides
Osteoclasts
Bone Resorption
Osteogenesis
Bone Density Conservation Agents
Bone Diseases
Osteoblasts
Coloring Agents
Down-Regulation
Genes
salicylanilide
oxazine 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Medicine(all)

Cite this

Modified salicylanilide and 3-phenyl-2 H -benzo[ e ][1,3]oxazine-2,4(3 H)-dione derivatives as novel inhibitors of osteoclast differentiation and bone resorption. / Chen, Chun Liang; Liu, Fei Lan; Lee, Chia Chung; Chen, Tsung Chih; Ahmed Ali, Ahmed Atef; Sytwu, Huey Kang; Chang, Deh Ming; Huang, Hsu Shan.

In: Journal of Medicinal Chemistry, Vol. 57, No. 19, 09.10.2014, p. 8072-8085.

Research output: Contribution to journalArticle

Chen, Chun Liang ; Liu, Fei Lan ; Lee, Chia Chung ; Chen, Tsung Chih ; Ahmed Ali, Ahmed Atef ; Sytwu, Huey Kang ; Chang, Deh Ming ; Huang, Hsu Shan. / Modified salicylanilide and 3-phenyl-2 H -benzo[ e ][1,3]oxazine-2,4(3 H)-dione derivatives as novel inhibitors of osteoclast differentiation and bone resorption. In: Journal of Medicinal Chemistry. 2014 ; Vol. 57, No. 19. pp. 8072-8085.
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