Premium
Development of 1‐Amino‐4‐(phenylamino)anthraquinone‐2‐sulfonate Sodium Derivatives as a New Class of Inhibitors of RANKL‐Induced Osteoclastogenesis
Author(s) -
Lee ChiaChung,
Chen ChunLiang,
Liu FeiLan,
Chiou ChungYu,
Chen TsungChih,
Wu ChengChi,
Sun WeiHsin,
Chang DehMing,
Huang HsuShan
Publication year - 2016
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201500475
Subject(s) - chemistry , rankl , anthraquinone , osteoclast , cytotoxicity , bone resorption , activator (genetics) , sulfonate , resorption , biochemistry , stereochemistry , sodium , in vitro , receptor , organic chemistry , medicine
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.