Fluorophore-Labeled Cyclooxygenase-2 Inhibitors for the Imaging of Cyclooxygenase-2 Overexpression in Cancer: Synthesis and Biological Studies

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 (14), 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). Targeted imaging: The association between cyclooxygenase‐2 (COX‐2) isozyme overexpression and the development of several kinds of human cancer make COX‐2 an attractive target for the design of new cancer biomarkers. Herein we describe the synthesis and biological evaluation of a group of fluorescent COX‐2 inhibitors for imaging cancer cells that overexpress COX‐2.