2. Academic Validation
  3. Synthesis and biological evaluation of amino-conjugated bile acid derivatives against non-alcoholic steatohepatitis

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

  • Bioorg Med Chem Lett. 2025 Jul 1:122:130210. doi: 10.1016/j.bmcl.2025.130210.
Zhitao Wu 1,  Mingge Zhang 2,  Meng Kun Yan 2,  Chenyue Li 3,  Guoyu Pan 4,  Lijiang Xuan 5
Affiliations

Affiliations

  • 1 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210029, China; State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China.
  • 2 State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China.
  • 3 State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China; School of Pharmacy, Fudan University, Shanghai 201203, PR China.
  • 4 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210029, China; State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China. Electronic address: gypan@simm.ac.cn.
  • 5 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210029, China; State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China. Electronic address: ljxuan@simm.ac.cn.
PMID: 40139332 DOI: 10.1016/j.bmcl.2025.130210
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.

Keywords

Anti-fibrosis activities; Anti-inflammatory activities; Anti-lipid accumulation activities; Bile acid derivatives; Non-alcoholic steatohepatitis (NASH).

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