title: Synthesis of lipophilic genistein derivatives and their regulation of IL-12 and TNF-α in activated J774A.1 cells.
abstract: Genistein modulates inflammatory responses in part by reducing the production of the pro-inflammatory cytokines IL-12, TNF-α, and nitric oxide, by activated macrophages in response to lipopolysaccharide stimulus. Previous studies have shown that synthetic lipophilic genistein glycosides were significantly more active than hydrophilic glycosides. The aims of this study were to synthesize and to evaluate the effect of novel lipophilic genistein derivatives on IL-12, TNF-α, and nitric oxide production by J774A.1 cells. The results show that the modification of genistein enables the generation of non-cytotoxic compounds with increased IL-12 inhibition. However, these derivatives failed to inhibit TNF-α. The nitric oxide production was notably inhibited by the monoester (2, 3) and monoether (6, 7) compounds in a dose-dependent manner.
authors.forename: Sandra B R
authors.initials: SB
authors.lastname: Castro
authors.forename: Celso O R
authors.initials: CO
authors.lastname: Junior
authors.forename: Caio C S
authors.initials: CC
authors.lastname: Alves
authors.forename: Alyria T
authors.initials: AT
authors.lastname: Dias
authors.forename: Lívia L
authors.initials: LL
authors.lastname: Alves
authors.forename: Luciano
authors.initials: L
authors.lastname: Mazzoccoli
authors.forename: Mateus T
authors.initials: MT
authors.lastname: Zoet
authors.forename: Sérgio A
authors.initials: SA
authors.lastname: Fernandes
authors.forename: Henrique C
authors.initials: HC
authors.lastname: Teixeira
authors.forename: Mauro V
authors.initials: MV
authors.lastname: Almeida
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D019833:Genistein / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D018664:Interleukin-12 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; D019833:Genistein