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Structural Optimization of Isoquinoline Derivatives from Lycobetaine and Their Inhibitory Activity against Neuroendocrine Prostate Cancer Cells

文献类型：期刊论文

作者Zhang, Zhuo7; Shen, Qianqian6; Ji, Yiyi5; Ma, Yanjie3,4; Hou, Haiyang2,6; Yang, Huajie4; Zhu, Yinjie5; Chen, Yi3,6; Hu, Youhong1,2,3,4,7
刊名MOLECULES
出版日期2024-09-01
卷号29期号:18页码:28
关键词NEPC natural product natural product derivatives lycobetaine
DOI10.3390/molecules29184503
通讯作者Zhu, Yinjie(yinjiezhu@outlook.com) ; Hu, Youhong(yhhu@simm.ac.cn)
英文摘要Neuroendocrine prostate cancer (NEPC) is a highly aggressive cancer that is resistant to hormone therapy and characterized by poor prognosis, as well as limited therapeutic options. Since the natural product lycobetaine was reported to exhibit good antitumor activities against various types of cancers, we initially simplified the scaffold of lycobetaine to obtain the active compound 1, an isoquinoline derivative with an aryl moiety substitution at the 4-position, which showed apparent antiproliferative activities against NPEC cell line LASCPC-01 in vitro. Subsequently, we carried out structural optimization and systematic structure-activity relationship (SAR) studies on compound 1, leading to the discovery of compound 46, which demonstrated potent inhibitory activities against the LASCPC-01 cell line with an IC50 value of 0.47 mu M. Moreover, compound 46 displayed remarkable selectivity over prostate cancer cell line PC-3 with a selectivity index greater than 190-fold. Further cell-based mechanism studies revealed that compound 46 and lycobetaine can effectively induce G1 cell cycle arrest and apoptosis dose dependently. However, lycobetaine inhibited the expression of neuroendocrine markers, while compound 46 slightly upregulated these proteins. This suggested that compound 46 might exert its antitumor activities through a different mechanism than lycobetaine, warranting further study.
WOS关键词L-DOPA DECARBOXYLASE ; ANDROGEN RECEPTOR ; UNGEREMINE ; GROWTH
资助项目Shandong Laboratory Program ; [SYS202205]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:001323477100001
出版者MDPI
源URL[http://119.78.100.183/handle/2S10ELR8/313657]  
专题新药研究国家重点实验室
通讯作者Zhu, Yinjie; Hu, Youhong
作者单位1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, 1st Xiangshan Branch Alley, Hangzhou 310024, Peoples R China
2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
3.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu ChongZhi Rd, Shanghai 201203, Peoples R China
5.Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Urol, Shanghai 200127, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
7.Nanjing Univ Chinese Med, Coll Pharm, Sch Chinese Mat Med, 138 Xianlin Rd, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Zhuo,Shen, Qianqian,Ji, Yiyi,et al. Structural Optimization of Isoquinoline Derivatives from Lycobetaine and Their Inhibitory Activity against Neuroendocrine Prostate Cancer Cells[J]. MOLECULES,2024,29(18):28.
APA Zhang, Zhuo.,Shen, Qianqian.,Ji, Yiyi.,Ma, Yanjie.,Hou, Haiyang.,...&Hu, Youhong.(2024).Structural Optimization of Isoquinoline Derivatives from Lycobetaine and Their Inhibitory Activity against Neuroendocrine Prostate Cancer Cells.MOLECULES,29(18),28.
MLA Zhang, Zhuo,et al."Structural Optimization of Isoquinoline Derivatives from Lycobetaine and Their Inhibitory Activity against Neuroendocrine Prostate Cancer Cells".MOLECULES 29.18(2024):28.

入库方式： OAI收割

来源：上海药物研究所

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