Theoretical prediction of the relationship between phenol function and COX-2/AP-1 inhibition for ferulic acid-related compounds. In vivo (Athens, Greece) [In Vivo] Journal article

Title	Theoretical prediction of the relationship between phenol function and COX-2/AP-1 inhibition for ferulic acid-related compounds.
Author(s)	Murakami Y, Ito S, Atsumi T, Fujisawa S
Institution	Department of Diagnostic Therapeutic Sciences, Meikai University School of Dentistry, Saitama 350-0283, Japan.
Source	In Vivo 2005 Nov-Dec; 19(6):1039-43.
MeSH	Animals Anti-Inflammatory Agents, Non-Steroidal Antioxidants Bicyclo Compounds, Heterocyclic Biphenyl Compounds Cell Line Comparative Study Coumaric Acids Cyclooxygenase 2 Inhibitors Dimerization Electrophoretic Mobility Shift Assay Eugenol Free Radical Scavengers Gene Expression Regulation Guaiacol Hydrazines Lipopolysaccharides Macrophages Mice Models, Chemical Models, Theoretical Phenol Research Support, Non-U.S. Gov't Structure-Activity Relationship Tetradecanoylphorbol Acetate Thermodynamics Transcription Factor AP-1
Abstract	Ferulic acid-related compounds possess antioxidant activity. Dehydrodiisoeugenol and ferulic acid dimer (bis-FA), but not the parent monomers isoeugenol and ferulic acid, inhibit lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2) gene expression in RAW 264.7 cells. To clarify the mechanism of their inhibitory effects on COX-2 expression, the phenolic O-H bond dissociation enthalpy (BDE) and ionization potential (IP) of 8 ferulic acid-related compounds were calculated by both semi-empirical molecular orbital (AM1, PM3) and ab initio (3-21G* 6-31G*) and density function theory (DFT) (B3LYP) methods. COX-2 inhibition appeared in compounds with phenolic O-H BDE higher than 85.76 kcal/mol, as calculated by the density function theory (DFT) approach. The phenolic O-H BDEs of the most potent compounds, dehydrodiisoeugenol and bis-FA, were 85.99 and 85.76 kcal/mol, respectively. No causal relationship between COX-2 inhibition and IP was found. Neither dehydrodiisoeugenol nor bis-FA possessed significant scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. The NSAID-like activity of dehydrodiisoeugenol and bis-FA appears to be related to their phenol function. Binding of activator protein-1 (AP-1) to the 12-tetradecanoylphorbol-13-acetate-responsive element (TRE) sequence in LPS-stimulated cells was inhibited by bis-FA at 1 microM and dehydrodiisoeugenol at 0.1 microM, but not by the parent monomers isoeugenol and ferulic acid.
Language	eng
Pub Type(s)	Journal Article
PubMed ID	16277019

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