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  3. Synthesis, evaluation and mechanism study of novel pyrazole enamides to alleviate lung injury

Synthesis, evaluation and mechanism study of novel pyrazole enamides to alleviate lung injury

  • Eur J Med Chem. 2025 Jan 15:282:117068. doi: 10.1016/j.ejmech.2024.117068.
Guoping Zhang 1,  Mengjie Li 2,  Yanghui Ou 2,  Liya Ma 1,  Jiayu Li 2,  Kexin Sun 1,  Tingting Xia 3,  Jingbo Wang 3,  Liyan Song 4,  Yang Liu 5,  Ran Lin 6,  Hongliang Yao 7
Affiliations

Affiliations

  • 1 Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Shaanxi Key Laboratory for Animal Conservation, College of Life Science, Northwest University, Xi'an, Shaanxi, 710069, China; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China.
  • 2 Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China.
  • 3 Department of Biopharmaceutical Sciences, College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou, Fujian, 350002, China.
  • 4 Key Laboratory of Biopesticide and Chemical Biology (Ministry of Education), College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.
  • 5 Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Shaanxi Key Laboratory for Animal Conservation, College of Life Science, Northwest University, Xi'an, Shaanxi, 710069, China; Department of Entomology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada. Electronic address: liuyangent@nwu.edu.cn.
  • 6 Department of Biopharmaceutical Sciences, College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou, Fujian, 350002, China. Electronic address: linran@fafu.edu.cn.
  • 7 Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China. Electronic address: yaohl@giz.gd.cn.
PMID: 39561496 DOI: 10.1016/j.ejmech.2024.117068
Abstract

Particulate matter with diameter ≤2.5 μm particles (PM2.5) can trigger pulmonary inflammation and lung injury. However, there is still no specific and effective treatment. Lansiumamide B (LB) is a natural cis-enamide compound isolated from wampee seeds, and has potential anti-inflammatory effect. Herein, two series of pyrazole enamide analogues were designed and synthesized based on the scaffold hopping strategy. The inhibition rates of inflammatory cytokines on compound 11a were superior to Other compounds and exhibited good dose-dependent manner and safety. Mechanism studies shown that 11a activated the Keap1/Nrf2/HO-1 signaling pathway and promoted Nrf2 entering into nucleus. Further, 11a alleviated pulmonary inflammation, collagen formation and mucus secretion in PM2.5 induced lung injury mice. Besides, 11a administration inhibited M1 macrophage polarization and neutrophil infiltration. Overall, 11a is an effective anti-inflammatory agent which might be a potent candidate to treat lung injury.

Keywords

Anti-Inflammation; Lung injury; Pyrazole enamides.

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