AI Article Synopsis
- A series of new 5-(2',4'-difluorophenyl)-salicylanide derivatives were created and tested for their ability to inhibit osteoclastogenesis induced by RANKL, with compounds 6d and 6i showing three times more potency than the lead compound NDMC101.
- Mechanistic studies revealed that these compounds suppress key genes related to osteoclast formation, such as NFATc1, c-fos, TRAP, and cathepsin K, while also inhibiting NF-κB and NFATc1 at the nuclear level.
- Additionally, 6d and 6i effectively reduced the bone-resorbing activity of osteoclasts in pit
Article Abstract
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-κB 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.
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| http://dx.doi.org/10.1016/j.ejmech.2015.05.015 | DOI Listing |
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