Discovery of 5-(2′,4′-difluorophenyl)-salicylanilides as new inhibitors of receptor activator of NF-κ°B ligand (RANKL)-induced osteoclastogenesis

Chia Chung Lee, Fei Lan Liu, Chun Liang Chen, Tsung Chih Chen, Deh Ming Chang, Hsu Shan Huang

研究成果: 雜誌貢獻文章同行評審

24 引文 斯高帕斯(Scopus)

摘要

To improve the inhibitory potency of lead compound NDMC101 on RANKL-induced osteoclastogenesis, a series of new 5-(2′,4′-difluorophenyl)-salicylanilide derivatives were synthesized and evaluated for osteoclast inhibition by using TRAP-staining assay. Among them, both of compounds 6d and 6i showed three-fold increase in osteoclast-inhibitory activities compared to NDMC101 at half-inhibitory concentration. Further, the mechanistic study showed that 6d and 6i could suppress RANKL-induced osteoclastogenesis-related genes, such as NFATc1, c-fos, TRAP, and cathepsin K. Their inhibitory activities were further confirmed by including specific inhibition of NF-κ°B and NFATc1 expression levels in nucleus. In addition, 6d and 6i also could significantly attenuate bone-resorbing activity of osteoclasts by performing pit formation assay. Thus, a new class of 5-(2′,4′-difluorophenyl)-salicylanilide derivatives may be considered as essential lead structures for the further development of anti-resorptive agents.
原文英語
頁(從 - 到)115-126
頁數12
期刊European Journal of Medicinal Chemistry
98
DOIs
出版狀態已發佈 - 5月 25 2015

ASJC Scopus subject areas

  • 藥物發現
  • 有機化學
  • 藥理

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