Inhibitory effect of β-diketones and their metal complexes on TNF-α induced expression of ICAM-1 on human endothelial cells

Recent reports show that the natural β-diketone curcumin displays important biological properties regarding the intercellular adhesion molecule-1 (ICAM-1), which plays a critical role in the immune responses and inflammation. In this study the ICAM-1 inhibitory activity of β-diketone compounds, which are curcumin models lacking aromatic peripheral hydroxyl and methoxy groups, along with some metal derivatives is investigated. β-Diketones are systematically more active than metal complexes and the best obtained inhibition is 75% for both groups. The best inhibitors are 4-benzoyl-3-methyl-1-phenyl-pyrazol-5-one (HQPh) among the ligands, and sodium benzoylacetonato among metal derivatives. These results appear in line with the reported antitumor activity of related species. Since 4-acyl-5-pyrazolones posses four tautomeric forms, those corresponding to HQPh were investigated using density functional theory. Docking of all HQPh tautomers on ICAM-1 protein was performed suggesting one keto-enol form favored to act in biological environment.

Here we design, synthesize and investigate the effect of several models of curcumin, namely, diketones lacking aromatic hydroxyl and methoxy groups, and their metal complexes on inhibition of TNF-α induced of ICAM-1 on human endothelial cells.Figure optionsDownload as PowerPoint slide