Fluorinated Kavalactone Inhibited RANKL-Induced Osteoclast Differentiation of RAW264 Cells
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- Kumagai Momochika
- Faculty of Fisheries, Kagoshima University Japan Food Research Laboratories Department of Chemistry, Graduate School of Science, Osaka City University
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- Nishikawa Keisuke
- Department of Chemistry, Graduate School of Science, Osaka City University
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- Mishima Takashi
- Japan Food Research Laboratories
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- Yoshida Izumi
- Japan Food Research Laboratories
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- Ide Masahiro
- Japan Food Research Laboratories
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- Watanabe Akio
- Research Institute for Biological Functions, Chubu University
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- Fujita Kazuhiro
- Japan Food Research Laboratories
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- Morimoto Yoshiki
- Department of Chemistry, Graduate School of Science, Osaka City University
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Abstract
<p>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.</p>
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 43 (5), 898-903, 2020-05-01
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390566775132308480
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- NII Article ID
- 130007839305
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 030401782
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- PubMed
- 32378565
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed