2. Academic Validation
  3. Design and synthesis of 7-O-1,2,3-triazole hesperetin derivatives to relieve inflammation of acute liver injury in mice

Design and synthesis of 7-O-1,2,3-triazole hesperetin derivatives to relieve inflammation of acute liver injury in mice

  • Eur J Med Chem. 2021 Mar 5:213:113162. doi: 10.1016/j.ejmech.2021.113162.
Yan Zheng 1,  Yi-Long Zhang 2,  Zeng Li 2,  Wen Shi 2,  Ya-Ru Ji 2,  Ya-Hui Guo 3,  Cheng Huang 2,  Guo-Ping Sun 4,  Jun Li 5
Affiliations

Affiliations

  • 1 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China; Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, 230032, Anhui, China; Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China; The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Hefei, 230032, China.
  • 2 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China; The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Hefei, 230032, China.
  • 3 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China.
  • 4 Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, 230032, Anhui, China; Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China. Electronic address: sungp@ahmu.edu.cn.
  • 5 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, 230032, China; The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Hefei, 230032, China. Electronic address: lj@ahmu.edu.cn.
PMID: 33493826 DOI: 10.1016/j.ejmech.2021.113162
Abstract

Based on the previous research results of our research group, to further improve the anti-inflammatory activity of hesperetin, we substituted triazole at the 7-OH branch of hesperetin. We also evaluated the anti-inflammatory activity of 39 new hesperetin derivatives. All compounds showed inhibitory effects on nitric oxide (NO) and inflammatory factors in lipopolysaccharide-induced RAW264.7 cells. Compound d5 showed a strong inhibitory effect on NO (half maximal inhibitory concentration = 2.34 ± 0.7 μM) and tumor necrosis factor-α, interleukin (IL)-1β, and (IL-6). Structure-activity relationships indicate that 7-O-triazole is buried in a medium-sized hydrophobic cavity that binds to the receptor. Compound d5 can also reduce the Reactive Oxygen Species production and significantly inhibit the expression of inducible NO Synthase and cyclooxygenase-2 through the nuclear factor-κB signaling pathway. In vivo results indicate that d5 can reduce liver inflammation in mice with acute liver injury (ALI) induced by CCI4. In conclusion, d5 may be a candidate drug for treating inflammation associated with ALI.

Keywords

Anti-inflammatory activity introduction; Hesperetin; Structure-activity relationships; Synthesis; Triazole.

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