title: Synthesis and Biological Evaluation of Novel Resveratrol-NSAID Derivatives as Anti-inflammatory Agents.
abstract: Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may cause serious side effects such as gastric mucosal damage. Resveratrol, a naturally dietary polyphenol, exhibited anti-inflammatory activity and a protective effect against gastric mucosa damage induced by NSAIDs. In this regard, we synthesized a series of resveratrol-based NSAIDs derivatives and evaluated their anti-inflammatory activity against nitric oxide (NO) overproduction in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We identified mono-substituted resveratrol-ibuprofen combination 21 as the most potent anti-inflammatory agent, which is more active than a physical mixture of ibuprofen and resveratrol, individual ibuprofen, or individual resveratrol. In addition, compound 21 exerted potent inhibitory effects on the LPS-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Furthermore, compound 21 significantly increased the survival rate in an LPS-induced acute inflammatory model and produced markedly less gastric damage than ibuprofen. It was found that compound 21 may be a potent anti-inflammatory agent for the treatment of inflammation-related diseases.
authors.affiliation: Institute of Natural Medicinal Chemistry & Green Chemistry, Department of Pharmaceutical Engineering, School of Light Industry and Chemical Engineering, Guangdong University of Technology.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Ma
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Ai-Yu
authors.initials: AY
authors.lastname: Zhou
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Huaqian
authors.initials: H
authors.lastname: Wang
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Du
authors.forename: Deng-Gao
authors.initials: DG
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005753:Gastric Mucosa / Q000187:drug effects; D007052:Ibuprofen / Q000737:chemistry; D053583:Interleukin-1beta / Q000032:analysis; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D000067996:RAW 264.7 Cells; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000077185:Resveratrol; D007052:Ibuprofen