Fluorophore-labeled cyclooxygenase-2 inhibitors for the imaging of cyclooxygenase-2 overexpression in cancer: synthesis and biological studies.

Abstract

A group of cyclooxygenase-2 (COX-2)-specific fluorescent cancer biomarkers were synthesized by linking the anti-inflammatory drugs ibuprofen, (S)-naproxen, and celecoxib to the 7-nitrobenzofurazan (NBD) fluorophore. In vitro COX-1/COX-2 inhibition studies indicated that all of these fluorescent conjugates are COX-2 inhibitors (IC₅₀ range: 0.19-23.0 μM) with an appreciable COX-2 selectivity index (SI≥4.3-444). In this study the celecoxib-NBD conjugate N-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethyl)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, which displayed the highest COX-2 inhibitory potency and selectivity (COX-2 IC₅₀ =0.19 μM; SI=443.6), was identified as an impending COX-2-specific biomarker for the fluorescence imaging of cancer using a COX-2-expressing human colon cancer cell line (HCA-7).

• Authors: Atul Bhardwaj, Jatinder Kaur, Frank Wuest, Edward E Knaus
• Journal: ChemMedChem (ChemMedChem) Vol. 9 Issue 1 Pg. 109-16, 240 (Jan 2014) ISSN: 1860-7187 [Electronic] Germany
• PMID: 24376205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Fluorescent Dyes
• Pyrazoles
• Sulfonamides
• celecoxib-NBD
• Naproxen
• Cyclooxygenase 1
• Cyclooxygenase 2
• PTGS2 protein, human
• 4-Chloro-7-nitrobenzofurazan
• Celecoxib
• Ibuprofen

Topics

• 4-Chloro-7-nitrobenzofurazan (analogs & derivatives, chemistry)
• Anti-Inflammatory Agents, Non-Steroidal (chemistry)
• Celecoxib (analogs & derivatives, chemistry)
• Cell Line, Tumor
• Colonic Neoplasms (metabolism, pathology)
• Cyclooxygenase 1 (chemistry, metabolism)
• Cyclooxygenase 2 (chemistry, metabolism)
• Cyclooxygenase 2 Inhibitors (chemical synthesis, chemistry, metabolism)
• Cyclooxygenase Inhibitors (chemical synthesis, chemistry, metabolism)
• Fluorescent Dyes (chemistry)
• HCT116 Cells
• Humans
• Ibuprofen (chemistry)
• Microscopy, Confocal
• Naproxen (chemistry)
• Protein Binding
• Pyrazoles (chemistry)
• Sulfonamides (chemistry)