Synthesis and Antiosteoporotic Characterization of Diselenyl Maleimides: Discovery of a Potent Agent for the Treatment of Osteoporosis by Targeting RANKL

doi:10.1021/acs.jmedchem.4c01105

科研成果详情

题名	Synthesis and Antiosteoporotic Characterization of Diselenyl Maleimides: Discovery of a Potent Agent for the Treatment of Osteoporosis by Targeting RANKL
作者	Bin Li1; Yao Wu2,3; Linkun Ying2,3; Weiwei Zhu3; Jingyi Yang 4; Lingling Zhou2,3; Lele Yi2,3; Tianle Jiang1; Haofu Jiang1; Xiangrui Song2,3; Weiwei Xue 4; Guang Liang3,5; Shengbin Huang1; Zengqiang Song2,3
发表日期	2024-09-19
发表期刊	Journal of Medicinal Chemistry 影响因子和分区
语种	英语
原始文献类型	Journal Article
其他关键词	OSTEOCLAST DIFFERENTIATION ; BONE ; SELENIUM
摘要	To discover new osteoclast-targeting antiosteoporosis agents, we identified forty-six diselenyl maleimides, which were efficiently prepared using a novel, simple, and metal-free method at room temperature in a short reaction time. Among them, 3k showed the most marked inhibition of osteoclast differentiation with an IC50 value of 0.36 ± 0.03 μM. Moreover, 3k significantly suppressed RANKL-induced osteoclast formation, bone resorption, and osteoclast-specific genes expression in vitro. Mechanistic studies revealed that 3k remarkably blocked the RANKL-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways. In ovariectomized mice, intragastric administration of 3k significantly alleviated bone loss, exhibiting an effect similar to that of alendronate. Surface plasmon resonance assay and microscale thermophoresis assay results suggested that RANKL might be a potential molecular target for 3k. Collectively, the findings presented above provided a novel candidate for further development of bone antiresorptive drugs that target RANKL
资助项目	National Natural Science Foundation of China [22077096]; Natural Science Foundation of Zhejiang Province [LY23B020006]; Scientific Research Center of Wenzhou Medical University
出版者	AMER CHEMICAL SOC
ISSN	0022-2623
EISSN	1520-4804
卷号	67 期号:19 页码:17226-17242
DOI	10.1021/acs.jmedchem.4c01105
页数	17
WOS类目	Chemistry, Medicinal
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001318702300001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	39299698
SCOPUSEID	2-s2.0-85204896706
通讯作者地址	[Huang, Shengbin]Wenzhou Med Univ, Sch & Hosp Stomatol, Inst Stomatol, Wenzhou 325027, Peoples R China. ; [Song, Zengqiang]Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China. ; [Liang, Guang;Song, Zengqiang]Wenzhou Med Univ, Sch Pharmaceut Sci, State Key Lab Macromol Drugs & Large Scale Mfg, Wenzhou 325035, Zhejiang, Peoples R China. ; [Liang, Guang]Hangzhou Med Coll, Sch Pharm, Hangzhou 311399, Zhejiang, Peoples R China.
Scopus学科分类	Molecular Medicine;Drug Discovery
SCOPUS_ID	SCOPUS_ID:85204896706
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/218934
专题	口腔医学院、附属口腔医院药学院（分析测试中心）口腔医学院、附属口腔医院_口腔医学研究所
作者单位	1.Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, No. 373, Xueyuan West Road, Lucheng District, Wenzhou 325027, PR China.; 2.School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.; 3.State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.; 4.School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China.; 5.School of Pharmacy, Hangzhou Medical College, Hangzhou 311399, Zhejiang, China.
第一作者单位	口腔医学院、附属口腔医院; 口腔医学研究所
通讯作者单位	口腔医学院、附属口腔医院; 口腔医学研究所; 药学院（分析测试中心）
第一作者的第一单位	口腔医学院、附属口腔医院
推荐引用方式 GB/T 7714	Bin Li,Yao Wu,Linkun Ying,et al. Synthesis and Antiosteoporotic Characterization of Diselenyl Maleimides: Discovery of a Potent Agent for the Treatment of Osteoporosis by Targeting RANKL[J]. Journal of Medicinal Chemistry,2024,67(19):17226-17242.
APA	Bin Li., Yao Wu., Linkun Ying., Weiwei Zhu., Jingyi Yang., ... & Zengqiang Song. (2024). Synthesis and Antiosteoporotic Characterization of Diselenyl Maleimides: Discovery of a Potent Agent for the Treatment of Osteoporosis by Targeting RANKL. Journal of Medicinal Chemistry, 67(19), 17226-17242.
MLA	Bin Li,et al."Synthesis and Antiosteoporotic Characterization of Diselenyl Maleimides: Discovery of a Potent Agent for the Treatment of Osteoporosis by Targeting RANKL".Journal of Medicinal Chemistry 67.19(2024):17226-17242.