title: Novel diether compounds inhibiting differentiation of osteoclasts.
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.
authors.affiliation: College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Doh
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, Republic of Korea.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ting
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, Republic of Korea. myim@soomyung.ac.kr.
authors.forename: Mijung
authors.initials: M
authors.lastname: Yim
authors.affiliation: College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea. hypark@ewha.ac.kr.
authors.forename: Hea-Young Park
authors.initials: HP
authors.lastname: Choo
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D004987:Ethers / Q000138:chemical synthesis / Q000494:pharmacology*; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D013997:Time Factors
chemical_list: D050071:Bone Density Conservation Agents; D004987:Ethers; D008070:Lipopolysaccharides; D053245:RANK Ligand
keywords: Differentiation; Osteoclast; Osteoporosis; RANKL