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Fluorophore‐Labeled Cyclooxygenase‐2 Inhibitors for the Imaging of Cyclooxygenase‐2 Overexpression in Cancer: Synthesis and Biological Studies
Author(s) -
Bhardwaj Atul,
Kaur Jatinder,
Wuest Frank,
Knaus Edward E.
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300355
Subject(s) - cyclooxygenase , chemistry , celecoxib , fluorophore , conjugate , naproxen , in vitro , enzyme , cancer , etodolac , fluorescence , pharmacology , biochemistry , stereochemistry , medicine , pathology , physics , alternative medicine , mathematics , mathematical analysis , quantum mechanics
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 (IC 50 range: 0.19–23.0 μ M ) 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)‐1 H ‐pyrazol‐1‐yl)benzenesulfonamide ( 14 ), which displayed the highest COX‐2 inhibitory potency and selectivity (COX‐2 IC 50 =0.19 μ M ; 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).