title: Hesperetin derivatives: Synthesis and anti-inflammatory activity.
abstract: 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 logP values, among them, compounds 3c, 3e and 3i with minus logP 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.
authors: School of Pharmacy, Anhui Medical University, Hefei, China.
authors: Qian-Qian
authors: QQ
authors: Wang
authors: School of Pharmacy, Anhui Medical University, Hefei, China.
authors: Jing-Bo
authors: JB
authors: Shi
authors: School of Pharmacy, Anhui Medical University, Hefei, China.
authors: Chen
authors: C
authors: Chen
authors: School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory for Bioactivity of Natural Medicine of Anhui Province, Hefei, China.
authors: Cheng
authors: C
authors: Huang
authors: School of Pharmacy, Anhui Medical University, Hefei, China. Electronic address: ahmupharm@126.com.
authors: Wen-Jian
authors: WJ
authors: Tang
authors: School of Pharmacy, Anhui Medical University, Hefei, China; Key Laboratory for Bioactivity of Natural Medicine of Anhui Province, Hefei, China. Electronic address: lj@ahmu.edu.cn.
authors: Jun
authors: J
authors: Li
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006569:Hesperidin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006569:Hesperidin; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C013015:hesperetin
keywords: Anti-inflammatory activity; Hesperetin; Mannich base; Partition coefficient