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

被引：39

作者：

Bhardwaj, Atul ^{[1
,2
]}

Kaur, Jatinder ^{[1
,2
]}

Wuest, Frank ^{[1
]}

Knaus, Edward E. ^{[1
]}

机构：

[1] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2E1, Canada

[2] Univ Alberta, Dept Oncol, Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada

来源：

CHEMMEDCHEM | 2014年 / 9卷 / 01期

基金：

加拿大健康研究院;

关键词：

cancer; cyclooxygenases; enzymes; fluorescence; inhibitors; medicinal chemistry; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COX-2; INHIBITORS; AGENTS; PREVENTION; CHEMOPREVENTION; INFLAMMATION; APOPTOSIS; CELECOXIB; ASPIRIN;

D O I：

10.1002/cmdc.201300355

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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: 0.19-23.0M) with an appreciable COX-2 selectivity index (SI4.3-444). 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=0.19M; 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).

引用

页码：109 / 116

页数：8

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