Design, synthesis and biological evaluation of Alisol B derivatives for potential treatment of non-alcoholic steatohepatitis
文献类型：期刊论文
| 作者 | Yu, Nai-Rong1,3; Huang, Suling2 ; Deng, Zhen-Tao3; Wang, Jiayue1,2; Shen, Yu2; Leng, Ying1,2; Zhao, Qin-Shi1,3
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| 刊名 | BIOORGANIC CHEMISTRY
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| 出版日期 | 2025-02-01 |
| 卷号 | 155页码:15 |
| 关键词 | Non-alcoholic steatohepatitis (NASH) Alisol B Structural modification Structure-activity relationship HFD+CCl4-induced NASH mice model |
| ISSN号 | 0045-2068 |
| DOI | 10.1016/j.bioorg.2025.108132 |
| 英文摘要 | Non-alcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction- associated with fatty liver disease (MAFLD), is one of the most prevalent chronic liver diseases globally. NAFLD is characterized by the accumulation of liver fat unrelated to excessive alcohol consumption. Non-alcoholic steatohepatitis (NASH) is the disease progression of NAFLD and could develop into cirrhosis and hepatocellular carcinoma. In previous studies, the preclinical efficacy of alisol B and alisol B 23-acetate against NASH and metabolic syndrome was identified. However, there is a paucity of literature pertaining to the specialized structural optimization of alisol B for the treatment of NASH. In this study, a series of alisol B derivatives (1-21) were designed, synthesized and evaluated in order to improve the activity of alisol B and to obtain candidate compounds for treating NASH. The effects of the synthesized compounds on de novo lipogenesis and alpha-SMA gene expression were tested to explore the preliminary structure-activity relationship (SAR). Compounds 14 and 21 were selected for further in vivo investigation. The high-fat diet plus carbon tetrachloride (HFD + CCl4)-induced NASH mice model was employed for biological evaluation in vivo. Compounds 14 and 21 effectively improved hepatic steatosis, ballooning, inflammatory infiltration, and hepatic fibrosis in the livers of HFD + CCl4 mice. Thus, 14 and 21 are promising lead compounds for the treatment of NASH. |
| WOS关键词 | DE-NOVO LIPOGENESIS ; OBETICHOLIC ACID ; MULTICENTER ; INHIBITORS ; ORIENTALE ; RHIZOME ; PHASE-3 |
| 资助项目 | State Key laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM2205KF-08] ; Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China[P2022-KF06] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001417521500001 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316221]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Leng, Ying; Zhao, Qin-Shi |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Chi, Kunming 650201, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, Nai-Rong,Huang, Suling,Deng, Zhen-Tao,et al. Design, synthesis and biological evaluation of Alisol B derivatives for potential treatment of non-alcoholic steatohepatitis[J]. BIOORGANIC CHEMISTRY,2025,155:15. |
| APA | Yu, Nai-Rong.,Huang, Suling.,Deng, Zhen-Tao.,Wang, Jiayue.,Shen, Yu.,...&Zhao, Qin-Shi.(2025).Design, synthesis and biological evaluation of Alisol B derivatives for potential treatment of non-alcoholic steatohepatitis.BIOORGANIC CHEMISTRY,155,15. |
| MLA | Yu, Nai-Rong,et al."Design, synthesis and biological evaluation of Alisol B derivatives for potential treatment of non-alcoholic steatohepatitis".BIOORGANIC CHEMISTRY 155(2025):15. |
入库方式： OAI收割
来源：上海药物研究所
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