中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Design, Synthesis, and Biological Evaluation of Peptidomimetic Tetrahydropyrrole Spirodihydroindolones as SARS-CoV-2 3CL Protease Inhibitors

文献类型：期刊论文

作者Hu, Liuyan5,6,7; Zhao, Zhi6,7; Zhang, Shujing8; Yang, Lei1,9; Cui, Wenjie2; Hu, Tianwen2; Suo, Jin9; Sun, Haiguo1,9; Zhang, Qiumeng9; Zhang, Leike4
刊名ACS MEDICINAL CHEMISTRY LETTERS
出版日期2025-04-14
卷号16期号:5页码:790-796
关键词COVID-19 SARS-CoV-2 3CL protease Peptidomimetic inhibitors Tetrahydropyrrole spirodihydroindolone
ISSN号1948-5875
DOI10.1021/acsmedchemlett.4c00637
英文摘要The 3CL protease (3CL(pro)) of SARS-CoV-2 is a key enzyme that plays an essential role in mediating viral replication and transcription. In this study, we synthesized and evaluated a series of peptidomimetic compounds containing a tetrahydropyrrole spirodihydroindolone moiety. Among the target compounds, 13c and 17d exhibited obvious 3CL(pro) inhibitory activities with IC50 = 3.71 and 6.21 nM, respectively. In metabolic stability testing of liver microsomes, compound 13c showed improved stability in human liver microsomes. In addition, 13c displayed significant anti-SARS-CoV-2 activity and high safety in Vero E6 cells (EC50 = 19.26 nM, SI > 400). Further investigations indicated that 13c showed potent activity against HCoV-OC43 and favorable safety in Huh7 cells (EC50 = 61 nM, SI > 100). These findings suggest that compound 13c is a promising lead compound in the development of novel 3CL(pro) inhibitors.
资助项目Shanghai Institute of Materia Medica[SIMM0120231003]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001466857900001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/317467]  
专题新药研究国家重点实验室
通讯作者Xu, Zhijian; Zhang, Yumin; Jiang, Xiangrui; Zhang, Yan
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Vigonvita Shanghai Co Ltd, Shanghai 201210, Peoples R China
3.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
4.Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China
5.Anhui Univ Chinese Med, Sch Pharm, Hefei 230012, Peoples R China
6.Yangtze Delta Drug Adv Res Inst, Nantong 226133, Peoples R China
7.Yangtze Delta Pharmaceut Coll, Nantong 226133, Peoples R China
8.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pediat, Wuhan 430022, Hubei, Peoples R China
9.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Hu, Liuyan,Zhao, Zhi,Zhang, Shujing,et al. Design, Synthesis, and Biological Evaluation of Peptidomimetic Tetrahydropyrrole Spirodihydroindolones as SARS-CoV-2 3CL Protease Inhibitors[J]. ACS MEDICINAL CHEMISTRY LETTERS,2025,16(5):790-796.
APA Hu, Liuyan.,Zhao, Zhi.,Zhang, Shujing.,Yang, Lei.,Cui, Wenjie.,...&Shen, Jingshan.(2025).Design, Synthesis, and Biological Evaluation of Peptidomimetic Tetrahydropyrrole Spirodihydroindolones as SARS-CoV-2 3CL Protease Inhibitors.ACS MEDICINAL CHEMISTRY LETTERS,16(5),790-796.
MLA Hu, Liuyan,et al."Design, Synthesis, and Biological Evaluation of Peptidomimetic Tetrahydropyrrole Spirodihydroindolones as SARS-CoV-2 3CL Protease Inhibitors".ACS MEDICINAL CHEMISTRY LETTERS 16.5(2025):790-796.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。