title: 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.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2E1 (Canada); Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 1Z2 (Canada).
authors.forename: Atul
authors.initials: A
authors.lastname: Bhardwaj
authors.forename: Jatinder
authors.initials: J
authors.lastname: Kaur
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
authors.forename: Edward E
authors.initials: EE
authors.lastname: Knaus
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D000068579:Celecoxib / Q000031:analogs & derivatives / Q000737:chemistry; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry*; D045325:HCT116 Cells; D006801:Humans; D007052:Ibuprofen / Q000737:chemistry; D018613:Microscopy, Confocal; D009288:Naproxen / Q000737:chemistry; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry; D000096926:Benzenesulfonamides
chemical_list: D009327:4-Chloro-7-nitrobenzofurazan; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000068579:Celecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005456:Fluorescent Dyes; D007052:Ibuprofen; D009288:Naproxen; D011720:Pyrazoles; D013449:Sulfonamides; C000608758:celecoxib-NBD; D000096926:Benzenesulfonamides; C496540:PTGS2 protein, human
keywords: cancer; cyclooxygenases; enzymes; fluorescence; inhibitors; medicinal chemistry