Novel Pyrazole Derivatives Effectively Inhibit Osteoclastogenesis, a Potential Target for Treating Osteoporosis

Ting Hao Kuo, Tzu Hung Lin, Rong Sen Yang, Sheng Chu Kuo, Wen Mei Fu, Hsin-Yi Hung

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

As human beings live longer, age-related diseases such as osteoporosis will become more prevalent. Intolerant side effects and poor responses to current treatments are observed. Therefore, novel effective therapeutic agents are greatly needed. Here, pyrazole derivatives were designed and synthesized, and their osteoclastogenesis inhibitory effects both in vitro and in vivo were evaluated. The most promising compound 13 with a 2-(dimethylamino)ethyl group inhibited markedly in vitro osteoclastogenesis as well as the bone resorption activity of osteoclasts. Compound 13 affected osteoclasts early proliferation and differentiation more than later fusion and maturation stages. In ovariectomized (OVX) mice, compound 13 can inhibit the loss of trabecular bone volume, trabecular bone number, and trabecular thickness. Moreover, compound 13 can antagonize OVX-induced reduction of serum bone resorption marker and then compensatory increase of the bone formation marker. To sum up, compound 13 has high potential to be developed into a novel therapeutic agent for treating osteoporosis in the future.

Original languageEnglish
Pages (from-to)4954-4963
Number of pages10
JournalJournal of Medicinal Chemistry
Volume58
Issue number12
DOIs
Publication statusPublished - 2015 Jun 25

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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