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
Rational Design and Synthesis of Novel Benzimidazole Derivatives as Potential β-Glucosidase Inhibitors

文献类型：期刊论文

作者Liu, Xu4; Sun, Ge2,3; Li, Fengxing4; Feng, Xia1; Jia, Tongguan4; Luo, Cheng2,3; Chen, Shijie2,3; Chen, Hua4
刊名LETTERS IN DRUG DESIGN & DISCOVERY
出版日期2024
卷号21期号:13页码:2674-2683
关键词beta-glucosidase inhibitors benzimidazole linker solvent-exposed region o-trihydroxyphenol iminosugar
ISSN号1570-1808
DOI10.2174/1570180820666230822141514
英文摘要Background beta-Glucosidase has a variety of biological functions. A structural model for a potential beta-glucosidase inhibitor has been proposed in the studies. Objective A series f new diaryl derivatives linked through benzimidazole have been randomly and rationally designed, synthesized, and evaluated for their inhibitory activities against beta-glucosidase (almond). The proposed structural model provides a new strategy for the design of potent beta-glucosidase inhibitors. Methods According to the model, a series of benzimidazole derivatives were designed and synthesized, and their inhibitory activity, Ki value, inhibitory type, and binding mode analysis (PDB ID: 2J7C) on beta-glucosidase (almond) were evaluated. Results Two compounds 7b and 7d were the best inhibitors with IC50 values of 7.86 mu M and 3.52 mu M, respectively. Their K-i values were calculated to be 9.91 mu M and 5.81 mu M, respectively. Conclusion The SAR analysis suggested that such benzimidazole derivatives might bind to the active site of beta-glucosidase mainly through hydrogen bonds on o-trihydroxyphenol; the additional phenyl ring on the other side towards the solvent-exposed region played a very important role in improving their inhibitory activity against beta-glucosidase.
资助项目National Natural Science Foundation of China (NSFC)[21772031] ; Natural Science Foundations of Hebei Province[B2019201398]
WOS研究方向Pharmacology & Pharmacy
WOS记录号WOS:001326854300015
出版者BENTHAM SCIENCE PUBL LTD
源URL[http://119.78.100.183/handle/2S10ELR8/313687]  
专题新药研究国家重点实验室
通讯作者Chen, Hua
作者单位1.Chongqing Univ Educ, Sch Biol & Chem Engn, Chongqing 400067, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Ctr Chem Biol, Drug Discovery & Design Ctr, State Key Lab Drug Res,Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Hebei Univ, Coll Chem & Environm Sci, Key Lab Chem Biol Hebei Prov, Baoding 071002, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Xu,Sun, Ge,Li, Fengxing,et al. Rational Design and Synthesis of Novel Benzimidazole Derivatives as Potential β-Glucosidase Inhibitors[J]. LETTERS IN DRUG DESIGN & DISCOVERY,2024,21(13):2674-2683.
APA Liu, Xu.,Sun, Ge.,Li, Fengxing.,Feng, Xia.,Jia, Tongguan.,...&Chen, Hua.(2024).Rational Design and Synthesis of Novel Benzimidazole Derivatives as Potential β-Glucosidase Inhibitors.LETTERS IN DRUG DESIGN & DISCOVERY,21(13),2674-2683.
MLA Liu, Xu,et al."Rational Design and Synthesis of Novel Benzimidazole Derivatives as Potential β-Glucosidase Inhibitors".LETTERS IN DRUG DESIGN & DISCOVERY 21.13(2024):2674-2683.

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。