Hesperetin derivatives: Synthesis and anti-inflammatory activity

Sixteen novel hesperetin derivatives containing Mannich base moiety were designed and synthesized and their anti-inflammatory activities were evaluated by inhibiting tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in mouse RAW264.7 macrophages. Compounds 3a–3k showed better hydrophilic, while compounds 3l–3p with aromatic groups was hydrophobic. The anti-inflammatory activity of title compounds was correlated with log P values, among them, compounds 3c, 3e and 3i with minus log P values exhibited best anti-inflammatory activity through decreasing both IL-6 and TNF-α. Furthermore, the expression of LPS-induced notch1 and inos was reduced by compounds 3c, 3e, and 3i, and compound 3e attenuated LPS-induced inos protein levels in a dose-dependent manner.

Graphical abstractNovel hesperetin derivatives exhibited higher anti-inflammatory activity through decreasing both IL-6 and TNF-α. Western blot analysis revealed that compound 3e inhibited LPS-induced notch1 and inos proteins in RAW264.7 macrophages.Figure optionsDownload full-size imageDownload as PowerPoint slide