Reference - Detail
| RRC ID | 62832 |
|---|---|
| Author | Kumagai M, Nishikawa K, Mishima T, Yoshida I, Ide M, Watanabe A, Fujita K, Morimoto Y. |
| Title | Fluorinated Kavalactone Inhibited RANKL-Induced Osteoclast Differentiation of RAW264 Cells. |
| Journal | Biol Pharm Bull |
| Abstract |
Bone loss and bone-related disease are associated with the deregulation of osteoclast function, and therefore agents that affect osteoclastogenesis have attracted attention. The purpose of the present study was to discover modified kavalactone analogs as potential anti-osteoclastogenic agents. We assessed the effect of 26 analogs on osteoclast differentiation in vitro. The most potent compound, (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one (22), suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenic differentiation of RAW264 cells with IC50 values of 4.3 µM. A partial structure-activity relationship study revealed the importance of fluorine and its position within the 5,6-dehydrokawain skeleton. The results of a pit formation assay suggested that compound 22 prevents osteoclastic bone resorption by inhibiting osteoclastogenesis. Moreover, compound 22 downregulated mRNA expression levels of RANKL-induced nuclear factor of activated T cells c1 (NFATc1) and osteoclastogenesis-related genes. These results suggest that (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one scaffold could lead to the identification of new anti-resorptive agents. |
| Volume | 43(5) |
| Pages | 898-903 |
| Published | 2020-1-1 |
| DOI | 10.1248/bpb.b20-00063 |
| PMID | 32378565 |
| MeSH | Animals Bone Resorption Cell Differentiation / drug effects Fluorine Lactones / pharmacology* Mice Osteoclasts / drug effects* Osteogenesis / drug effects Pyrones / pharmacology* RANK Ligand RAW 264.7 Cells Styrenes / pharmacology* |
| IF | 1.863 |
| Altmetric score |
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| The most frequently cited source | |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) |