Inhibitory effect of beta-diketones and their metal complexes on TNF-alpha induced expression of ICAM-1 on human endothelial cells.
Recent reports show that the natural beta-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 beta-diketone compounds, which are curcumin models lacking aromatic peripheral hydroxyl and methoxy groups, along with some metal derivatives is investigated. Beta-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 (HQ(Ph)) 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 HQ(Ph) were investigated using density functional theory. Docking of all HQ(Ph) tautomers on ICAM-1 protein was performed suggesting one keto-enol form favored to act in biological environment.
Caruso
Francesco
F
Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, c/o Università di Roma La Sapienza, Vecchio Istituto Chimico, Piazzale Aldo Moro 5, 00185 Rome, Italy. caruso@vassar.edu
Pettinari
Claudio
C
Marchetti
Fabio
F
Rossi
Miriam
M
Opazo
Cristian
C
Kumar
Sarvesh
S
Balwani
Sakshi
S
Ghosh
Balaram
B
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D020134:Catalytic Domain; D002478:Cells, Cultured; D003198:Computer Simulation; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry* / Q000378:metabolism; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D008670:Metals / Q000737:chemistry*; D008968:Molecular Conformation; D047069:Pyrazolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
C545030:4-benzoyl-3-methyl-1-phenyl-pyrazol-5-one; D000893:Anti-Inflammatory Agents; D007659:Ketones; D008670:Metals; D047069:Pyrazolones; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1