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

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.

• Authors: Yan Zheng, Yi-Long Zhang, Zeng Li, Wen Shi, Ya-Ru Ji, Ya-Hui Guo, Cheng Huang, Guo-Ping Sun, Jun Li
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 213 Pg. 113162 (Mar 05 2021) ISSN: 1768-3254 [Electronic] France
• PMID: 33493826 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Masson SAS. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Triazoles
• Nitric Oxide
• Carbon Tetrachloride
• Hesperidin
• hesperetin

Topics

• Animals
• Carbon Tetrachloride
• Cell Survival (drug effects)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Drug Design
• Hesperidin (chemical synthesis, chemistry, pharmacology)
• Inflammation (drug therapy, metabolism, pathology)
• Liver (drug effects, injuries, metabolism)
• Mice
• Mice, Inbred C57BL
• Molecular Structure
• Nitric Oxide (analysis, biosynthesis)
• RAW 264.7 Cells
• Reactive Oxygen Species (analysis, metabolism)
• Structure-Activity Relationship
• Triazoles (chemical synthesis, chemistry, pharmacology)