Synthesis and biological evaluation of amino-conjugated bile acid derivatives against non-alcoholic steatohepatitis

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-03-24 DOI:10.1016/j.bmcl.2025.130210

Zhitao Wu , Mingge Zhang , Meng Kun Yan , Chenyue Li , Guoyu Pan , Lijiang Xuan

{"title":"Synthesis and biological evaluation of amino-conjugated bile acid derivatives against non-alcoholic steatohepatitis","authors":"Zhitao Wu , Mingge Zhang , Meng Kun Yan , Chenyue Li , Guoyu Pan , Lijiang Xuan","doi":"10.1016/j.bmcl.2025.130210","DOIUrl":null,"url":null,"abstract":"<div><div>Non-alcoholic steatohepatitis (NASH) is emerging as a rapidly growing health concern. Bile acids (BAs) function as endocrine signaling molecules and exhibit therapeutic potential for NASH. To develop safer and more effective BA derivatives for NASH treatment, 25 amino acid-conjugated bile acid derivatives were designed and synthesized based on the pharmacological properties of the leading compound <strong>A17.</strong> The anti-lipid accumulation, anti-inflammatory and anti-fibrosis activities of these compounds were evaluated, and their structure-activity relationships were elucidated. Notably, compound <strong>C04</strong> exhibited superior in vitro activity compared to obeticholic acid and demonstrated enhanced efficacy in improving both NASH and fibrosis in preclinical murine models via oral administration. These findings suggest that <strong>C04</strong> is a promising candidate for NASH treatment and warrants further investigation.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"122 ","pages":"Article 130210"},"PeriodicalIF":2.5000,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry Letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960894X25001192","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Non-alcoholic steatohepatitis (NASH) is emerging as a rapidly growing health concern. Bile acids (BAs) function as endocrine signaling molecules and exhibit therapeutic potential for NASH. To develop safer and more effective BA derivatives for NASH treatment, 25 amino acid-conjugated bile acid derivatives were designed and synthesized based on the pharmacological properties of the leading compound A17. The anti-lipid accumulation, anti-inflammatory and anti-fibrosis activities of these compounds were evaluated, and their structure-activity relationships were elucidated. Notably, compound C04 exhibited superior in vitro activity compared to obeticholic acid and demonstrated enhanced efficacy in improving both NASH and fibrosis in preclinical murine models via oral administration. These findings suggest that C04 is a promising candidate for NASH treatment and warrants further investigation.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.