Synthesis and biological evaluation of rhein amides as inhibitors of osteoclast differentiation and bone resorption
文献类型：期刊论文
| 作者 | Xu, Xing1; Qi, Xueyu2,3; Yan, Yufei1; Qi, Jin1; Qian, Niandong1; Guo, Lei1; Li, Changwei1; Wang, Fei1; Huang, Ping1; Zhou, Hanbing1 |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2016-11-10 |
| 卷号 | 123页码:769-776 |
| 关键词 | Osteoclast Rhein derivatives Bone resorption Inhibitor RANKL/RANK/NFATc1 pathway |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2016.08.004 |
| 文献子类 | Article |
| 英文摘要 | Approaches of targeting excessive activation and differentiation of osteoclasts were considered as an effective treatment option for osteoporosis or osteopenia. In the present work, a series of rhein derivatives were synthesized and employed for their cytotoxicity screening against bone marrow-derived macrophages cells (BMMs) and their inhibition effects on osteoclasts activation and differentiation in vitro using an MTF assay and a TRAP activity assay respectively. Two rhein derivatives d6 and d11 inhibited BMMs activation and differentiation with 98% and 85% inhibitory activity respectively, without showing any cytotoxicity on BMMs. Subsequently, the most potent compound d6 was further validated for its inhibitory effects on the formation of TRAP-positive multinucleated cells and bone resorption as evaluated by TRAP staining and bone resorption assay. The regulation by d6 of osteoclast marker genes assay revealed that treatment of BMMs with M-CSF and RANK!, resulted in the stimulation of mRNA expressions of NFATc1, c-fos, TRAP, MMP-9 and cathepsin K which were highly related with osteoclast activation and differentiation, while d6 decreased mRNA expressions of these genes. It was indicated that d6 might regulate osteoclasts activity through RANKL/RANK/NFATc1 pathway. Thus our current work is expected to provide a highly promising approach for the development of a new type of anti-osteoporosis agent. (C) 2016 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | RANKL-INDUCED OSTEOCLASTOGENESIS ; POTENTIAL ANTICANCER AGENTS ; IN-VITRO ; DERIVATIVES ; OSTEOPOROSIS ; DISEASE ; DESIGN ; PATHOGENESIS ; HOMEOSTASIS |
| 资助项目 | NSFC[81321092] ; NSFC[81502902] ; Shanghai Municipal Health Bureau young scientific research project[20154Y0005] ; Shanghai Municipal Health Bureau young scientific research project[20144Y0055] ; Shanghai Committee of Science and Technology, China[14ZR1437500] ; Shanghai Committee of Science and Technology, China[16ZR1431900] ; Funding of Shanghai Jiao Tong University School of Medicine[14XJ10043] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000385319000061 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275816]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Jiang, Min; Yang, Chunhao |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Shanghai Inst Traumatol & Orthopaed, Shanghai Key Lab Bone & Joint Dis, Shanghai Ruijin Hosp,Sch Med, Shanghai 20025, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Xing,Qi, Xueyu,Yan, Yufei,et al. Synthesis and biological evaluation of rhein amides as inhibitors of osteoclast differentiation and bone resorption[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2016,123:769-776. |
| APA | Xu, Xing.,Qi, Xueyu.,Yan, Yufei.,Qi, Jin.,Qian, Niandong.,...&Deng, Lianfu.(2016).Synthesis and biological evaluation of rhein amides as inhibitors of osteoclast differentiation and bone resorption.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,123,769-776. |
| MLA | Xu, Xing,et al."Synthesis and biological evaluation of rhein amides as inhibitors of osteoclast differentiation and bone resorption".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 123(2016):769-776. |
入库方式： OAI收割
来源：上海药物研究所
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