Discovery, Synthesis of Myrtucommulone B Analogs as Soluble Epoxide Hydrolase Inhibitors and Their Biological Activities

  • J Med Chem. 2026 May 14;69(9):10240-10262. doi: 10.1021/acs.jmedchem.5c03313.
Jia-Rui Sun  1 ,  Shuang-Shuang Kang  2 ,  Bo-Lin Wang  1 ,  Xin-Ya Yang  1 ,  Yu Zhang  1
Affiliations
  • 1. School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, China.
  • 2. Institute of Quality and Safety for Agro-Products, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China.
PMID: 42013369 DOI: 10.1021/acs.jmedchem.5c03313
Abstract

No specific drugs exist for acute pancreatitis (AP). Soluble Epoxide Hydrolase (sEH) inhibitors hold therapeutic potential. Myrtus communis L. is a traditional herb with anti-inflammatory and antiseptic effects; however, the underlying mechanism of its anti-inflammatory activity remains unclear. Here, novel myrtucommulone B derivatives were synthesized and evaluated for their activity as sEH inhibitors. Bioassays showed derivative (+)-34 potently inhibited sEH, with low toxicity and robust in vitro/vivo anti-inflammatory and analgesic effects. Notably, (+)-34 showed significant protection in a murine AP model. Its in vivo mechanism involves elevating anti-inflammatory epoxyeicosatrienoic acids (EETs) and reducing proinflammatory dihydroxyeicosatrienoic acids (DHETs) by blocking sEH, thereby suppressing proinflammatory cytokines (TNF-α, IL-6). This study lays a foundation for developing myrtucommulone-based sEH inhibitors as novel anti-inflammatory/analgesic agents, particularly potential therapeutics for AP.

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