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Novel diether compounds inhibiting differentiation of osteoclasts

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Abstract

Osteoporosis is a disorder in which bone mass decreases and is responsible for many degenerative bone diseases. The excessive formation and activity of osteoclasts results in pathological disorders of the bone. Receptor Activator of Nuclear Factor κB Ligand (RANKL) is regarded as a key regulator of osteoclast activity and as a new therapeutic target for treating osteoporosis. Herein, we have synthesized several new small molecules and tested their inhibition activity on RANKL-induced osteoclast formation. The active compounds 2c and 4d showed inhibitory activity against RANKL-induced osteoclast differentiation (IC50 = 1.56 and 2.20 μM, respectively). The most active compound 2c prevented LPS-induced osteoclastogenesis in vivo. These data imply that the compound may be the potential candidate for a new therapeutic drug for treatment of bone resorption-associated diseases.

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Acknowledgments

This research was supported by the Sookmyung Women’s University Research Grants (1-1303-0205).

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Authors and Affiliations

  1. College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea

    Kyung Eun Doh & Hea-Young Park Choo

  2. College of Pharmacy, Sookmyung Women’s University, Seoul, 140-742, Republic of Korea

    Ju-Hee Kang, Zheng Ting & Mijung Yim

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  1. Kyung Eun Doh
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  2. Ju-Hee Kang
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  3. Zheng Ting
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  4. Mijung Yim
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  5. Hea-Young Park Choo
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Correspondence to Mijung Yim or Hea-Young Park Choo.

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Doh, K.E., Kang, JH., Ting, Z. et al. Novel diether compounds inhibiting differentiation of osteoclasts. Arch. Pharm. Res. 39, 178–190 (2016). https://doi.org/10.1007/s12272-015-0672-x

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