Synthesis and biological evaluation of curcuminoid pyrazoles as new therapeutic agents in inflammatory bowel disease: Effect on matrix metalloproteinases

• Published in: Bioorganic & medicinal chemistry Vol. 17; no. 3; pp. 1290 - 1296
• Main Authors: Claramunt, R.M., Bouissane, L., Cabildo, M.P., Cornago, M.P., Elguero, J., Radziwon, A., Medina, C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.02.2009; Elsevier
• Subjects: Biological and medical sciences; Caco-2 Cells; Crohn’s disease; Curcumin; Curcumin - chemical synthesis; Curcumin - chemistry; Curcumin - pharmacology; Digestive system; Gelatinases; Gelatinases - metabolism; Humans; Inflammatory bowel disease; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - enzymology; Interleukin-1beta - metabolism; Matrix Metalloproteinase Inhibitors; Matrix metalloproteinases; Medical sciences; Pharmacology. Drug treatments; Pyrazole; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Tumor Necrosis Factor-alpha - metabolism; Ulcerative colitis; Inflammatory bowel disease; Matrix metalloproteinases; Caco-2 cells; Gelatinases; Curcumin; Pyrazole; Crohn’s disease; Ulcerative colitis; Metalloendopeptidases; Inflammatory disease; Pyrazole derivatives; Intestinal disease; Colon; Chemical synthesis; Tumor necrosis factor α; Human; Enzyme; Gel electrophoresis; Cytokine; Interleukin 1β; Crohn's disease; In vitro; Biological activity; Gelatinase B; Peptidases; Crohn disease; Cell line; Phenols; Hydrolases; Digestive diseases; Zymography
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2008.12.029

Curcuminoid pyrazoles ( 1– 3), have demonstrated activity in the biological assays used as models (MMPs inhibition) for inflammatory bowel disease. Seven N-unsubstituted curcuminoid pyrazoles have been synthesized from the corresponding β-diketones (including curcumin). We evaluated the possibility of curcuminoid pyrazoles regulating the activity of matrix metalloproteinases (MMPs) by human intestinal epithelial cells in vitro. Zymographic analysis revealed that three compounds significantly down-regulated MMP-9 activity on inflammation-induced intestinal epithelial cells, making them original candidates for the treatment of inflammatory bowel disease (IBD).