Development of Fluorescence Imaging Probes for Labeling COX-1 in Live Ovarian Cancer Cells

Jatinder Kaur; Atul Bhardwaj; Frank Wuest

doi:10.1021/acsmedchemlett.1c00065

Development of Fluorescence Imaging Probes for Labeling COX-1 in Live Ovarian Cancer Cells

ACS Med Chem Lett. 2021 Apr 8;12(5):798-804. doi: 10.1021/acsmedchemlett.1c00065. eCollection 2021 May 13.

Authors

Jatinder Kaur^{1

2}, Atul Bhardwaj^{1

2}, Frank Wuest^{1

2

3}

Affiliations

¹ Department of Oncology, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada.
² Faculty of Pharmacy and Pharmaceutical Sciences University of Alberta, 8613 - 114 St., Edmonton, Alberta T6G 2H7, Canada.
³ Department of Chemistry, University of Alberta, 11227 Saskatchewan Drive, Edmonton, Alberta T6G 2G2, Canada.

Abstract

Recent experimental evidence demonstrated an aberrant overexpression of cyclooxygenase-1 (COX-1) in various cancers, which has stimulated the development of COX-1-selective inhibitors as promising anticancer drugs and cancer imaging agents. Herein we describe the synthesis and validation of 3-(furan-2-yl)-N-aryl 5-amino-pyrazoles as a novel class of COX-1 inhibitors, including molecular docking studies. Among all tested compounds, 4-(5-azido-3-(furan-2-yl)-1H-pyrazol-1-yl)benzoic 17 displayed a favorable COX-1 inhibition and selectivity profile (COX-1 IC₅₀ = 0.1 μM, SI >1000 over COX-2). Compound 17 was selected as a lead structure for developing the novel COX-1-selective fluorescent probe 22. Fluorescent probe 22 was prepared via click chemistry by installing a nitro-benzoxadiazole motif as a fluorophore into the 3-(furan-2-yl)-N-aryl 5-amino-pyrazole scaffold. Fluorescence probe 22 was tested in ovarian cancer cell line OVCAR-3, confirming its usefulness for targeting and visualizing COX-1 in living cells with confocal microscopy.