In vitro and in vivo anti-inflammatory properties of imine resveratrol analogues. Issue 17 (15th September 2018)

• Record Type: Journal Article
• Authors: Zimmermann-Franco, Danielle Cristina; Esteves, Bruna; Lacerda, Leticia Moroni; Souza, Isabela de Oliveira; Santos, Juliana Alves dos; Pinto, Nícolas de Castro Campos; Scio, Elita; da Silva, Adilson David; Macedo, Gilson Costa
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 17(2018)
• Page Start: 4898
• Page End: 4906
• Publication Date: 2018-09-15
• Subjects: 13C NMR carbon-13 nuclear magnetic resonance -- 1H NMR proton nuclear magnetic resonance -- 5-LOX 5-lipoxygenase -- AP-1 activator protein 1 -- AR resveratrol analogs -- BSA Bovine serum albumin -- CCL-2 C-C motif chemokine ligand 2 -- CD cluster of differentiation -- COX cyclooxygenase -- DMSO dimethyl sulfoxide -- DPPH 2, 2-diphenyl-1-picrylhydrazyl -- EDTA ethylenediamine tetraacetic acid -- ELISA enzyme-linked immunosorbent assay -- HE hematoxylin and eosin -- HTAB hexadecyl trimethyl ammonium bromide -- IC inhibitory concentration -- IFN-γ interferon-γ -- IL interleukin -- iNOS nitric oxide synthases -- LPS lipopolysaccharide -- MCP-1 monocyte chemoattractant protein 1 -- MHC major histocompatibility complex -- MPO myeloperoxidase -- MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) -- NF-κB nuclear factor-κB -- NO nitric oxide -- OD optical density -- OPD ophenylenediamine -- PMSF phenylmethylsulfonyl fluoride -- SD standard deviation -- TH T helper cell -- TMS tetramethylsilane -- TNF-α tumor necrosis factor-α -- v/v volume (of solute) per volume (of solvent); Resveratrol -- Analogues -- Imine -- Anti-inflammatory -- Immunomodulatory; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.08.029
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: Imines resveratrol analogues are less cytotoxicity than thioimines and hydrazones. The imines are more effective than resveratrol on DPPH scavenger. The imines reduce pro-inflammatory mediators production in vitro. The imines decrease lymphocyte proliferation and costimulatory molecules. The imines control edema formation, cytokines and myeloperoxidase production in vivo. Abstract: Resveratrol is a natural polyphenol found mainly on red grapes and in red wine, pointed as an important anti-inflammatory/immunomodulatory molecule. However, its bioavailability problems have limited its use encouraging the search for new alternatives agents. Thus, in this study, we synthetize 12 resveratrol analogues (6 imines, 1 thioimine and 5 hydrazones) and investigated its cytotoxicity, antioxidant activity and in vitro anti-inflammatory/immunomodulatory properties. The most promising compounds were also evaluated in vivo . The results showed that imines presented less cytotoxicity, were more effective than resveratrol on DPPH scavenger and exhibited an anti-inflammatory profile. Among them, the imines with a radical in the para position, on the ring B, not engaged in an intramolecular hydrogen-interaction, showed more prominent anti-inflammatory activity modulating, in vivo, the edema formation, the inflammatory infiltration and cytokine levels. An immunomodulatory activity also was observed in these molecules. Thus, our results suggest that imines with these characteristics presents potential to control inflammatory disorders.