Fluorophore‐Labeled Cyclooxygenase‐2 Inhibitors for the Imaging of Cyclooxygenase‐2 Overexpression in Cancer: Synthesis and Biological Studies. Issue 1 (31st October 2013)

• Record Type: Journal Article
• Authors: Bhardwaj, Atul; Kaur, Jatinder; Wuest, Frank; Knaus, Edward E.
• Is Part Of: ChemMedChem. Volume 9:Issue 1(2014:Jan.)
• Page Start: 109
• Page End: 116
• Publication Date: 2013-10-31
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201300355
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A group of cyclooxygenase‐2 (COX‐2)‐specific fluorescent cancer biomarkers were synthesized by linking the anti‐inflammatory drugs ibuprofen, (<italic>S</italic>)‐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 μ<sc>M</sc>) with an appreciable COX‐2 selectivity index (SI≥4.3–444). In this study the celecoxib–NBD conjugate <italic>N</italic>‐(2‐((7‐nitrobenzo[<italic>c</italic>][1, 2, 5]oxadiazol‐4‐yl)amino)ethyl)‐4‐(5‐(<italic>p</italic>‐tolyl)‐3‐(trifluoromethyl)‐1<italic>H</italic>‐pyrazol‐1‐yl)benzenesulfonamide (<bold>14</bold>), which displayed the highest COX‐2 inhibitory potency and selectivity (COX‐2 IC₅₀=0.19 μ<sc>M</sc>; 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).</p> </abstract>