2. Academic Validation
  3. Design, synthesis and evaluation of shikimic acid derivatives for the treatment of ulcerative colitis

Design, synthesis and evaluation of shikimic acid derivatives for the treatment of ulcerative colitis

  • Eur J Med Chem. 2026 May 5:309:118762. doi: 10.1016/j.ejmech.2026.118762.
Huiru Xie 1,  Zhipeng Wang 2,  Maojun Yao 2,  Shanshan Zhu 2,  Hong Yan 3,  Hualong Song 4,  Rubing Wang 5
Affiliations

Affiliations

  • 1 College of Chemistry and Life Science, Beijing University of Technology, Beijing, 100124, China.
  • 2 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
  • 3 College of Chemistry and Life Science, Beijing University of Technology, Beijing, 100124, China. Electronic address: hongyan@bjut.edu.cn.
  • 4 Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, School of Pharmaceutical Sciences, Capital Medical University, Beijing, 100069, China. Electronic address: hualong.song@ccmu.edu.cn.
  • 5 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: wangrubing@imm.ac.cn.
PMID: 41849950 DOI: 10.1016/j.ejmech.2026.118762
Abstract

Ulcerative colitis is a severe gastrointestinal disorder that can even affect multiple organs throughout the body. Therefore, developing innovative agents for the treatment of ulcerative colitis is of significant importance. In this study, sixty-four new compounds were designed and synthesized basing on the natural product shikimic acid, structurally featuring the integration of adamantane at its 1-position and various aromatic or heteroaromatic rings at 5-position. Among them, five compounds (77, 87, 110, 123, and 134) potently inhibited the inflammatory response in lipopolysaccharide-induced macrophages without detectable cytotoxicity. The structure-activity data acquired from the study validated the substitution type at 1-position was crucial and 6-membered heteroaromatic rings integration at 5-position of shikimic acid provided more potent derivatives for in-depth development of inflammatory diseases. Compound 110 significantly ameliorated colitis-related symptoms in DSS-induced ulcerative colitis mice and suppressed the levels of pro-inflammatory cytokines (TNF-α and IL-6) and downregulated the expression of key inflammatory mediators (COX-2 and iNOS) by inhibition of the PI3K/Akt signaling pathway. These findings collectively identify compound 110 as a promising lead compound for the treatment of ulcerative colitis.

Keywords

Anti-inflammatory; Natural product; Shikimic acid derivatives; Ulcerative colitis.

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