title: Development of 1-Amino-4-(phenylamino)anthraquinone-2-sulfonate Sodium Derivatives as a New Class of Inhibitors of RANKL-Induced Osteoclastogenesis.
abstract: A series of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium derivatives was synthesized and evaluated for osteoclast inhibition using a TRAP-staining assay. Among them, two compounds, LCCY-13 and LCCY-15, dose-dependently suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Moreover, the cytotoxicity assay on RAW264.7 cells suggested that the inhibition of osteoclastic bone resorption by these compounds was not a result of their cytotoxicity. Further, the inhibitory activities of compounds LCCY-13 and LCCY-15 were further confirmed by including specific inhibition of NFATc1 expression levels in nuclei using an immunofluorescent analysis. In addition, LCCY-13 and LCCY-15 also significantly attenuated the bone resorption activity of osteoclasts according to a pit formation assay. Thus, a new class of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium compounds might be considered as an essential lead structure for the further development of anti-resorptive agents.
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.|Rheumatology/Immunology/Allergy, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chia-Chung
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.|Rheumatology/Immunology/Allergy, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Rheumatology/Immunology/Allergy, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Fei-Lan
authors.initials: FL
authors.lastname: Liu
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Chiou
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Tsung-Chih
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Rheumatology/Immunology/Allergy, Taipei Veterans General Hospital, Taipei, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Cheng-Chi
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Life Sciences, National Central University, Jhongli City, Taiwan.
authors.forename: Wei-Hsin
authors.initials: WH
authors.lastname: Sun
authors.affiliation: Rheumatology/Immunology/Allergy, Taipei Veterans General Hospital, Taipei, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hsu-Shan
authors.initials: HS
authors.lastname: Huang
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D001862:Bone Resorption; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051379:Mice; D050778:NFATC Transcription Factors / Q000096:biosynthesis; D010010:Osteoclasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand
keywords: Anthraquinone derivatives; Osteoclastogenesis; RANKL; TRAP-staining assay