title: Pyrimidine-based fluorescent COX-2 inhibitors: synthesis and biological evaluation.
abstract: The cyclooxygenase-2 (COX-2) enzyme is overexpressed in a variety of cancers and mediates inflammatory processes that aid the growth and progression of malignancies. Three novel and selective fluorescent COX-2 inhibitors have been designed and synthesized on the basis of previously reported pyrimidine-based COX-2 inhibitors and the 7-nitrobenzofurazan fluorophore. In vitro evaluation of COX-1/COX-2 isozyme inhibition identified N-(2-((7-nitro-benzo[c][1,2,5]oxadiazol-4-yl)amino)propyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoro-methyl)-pyrimidin-2-amine (6) as a novel potent and selective COX-2 inhibitor (IC50 = 1.8 μM). Lead compound (6) was further evaluated for its ability to selectively visualize COX-2 isozyme in COX-2 expressing human colon cancer cell line HCA-7 using confocal microscopy experiments.
authors.affiliation: Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, T6G 1Z2, Edmonton, AB, Canada. ole@ualberta.ca kaur2@ualberta.ca abhardwa@ualberta.ca wuest@ualberta.ca.
authors.forename: Ole
authors.initials: O
authors.lastname: Tietz
authors.affiliation: Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, T6G 1Z2, Edmonton, AB, Canada. ole@ualberta.ca kaur2@ualberta.ca abhardwa@ualberta.ca wuest@ualberta.ca and Department of Pharmacy and Pharmaceutical Sciences, Medical Sciences Building, University of Alberta, T6G 2H1, Edmonton, AB, Canada.
authors.forename: Jatinder
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, T6G 1Z2, Edmonton, AB, Canada. ole@ualberta.ca kaur2@ualberta.ca abhardwa@ualberta.ca wuest@ualberta.ca and Department of Pharmacy and Pharmaceutical Sciences, Medical Sciences Building, University of Alberta, T6G 2H1, Edmonton, AB, Canada.
authors.forename: Atul
authors.initials: A
authors.lastname: Bhardwaj
authors.affiliation: Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, T6G 1Z2, Edmonton, AB, Canada. ole@ualberta.ca kaur2@ualberta.ca abhardwa@ualberta.ca wuest@ualberta.ca and Department of Pharmacy and Pharmaceutical Sciences, Medical Sciences Building, University of Alberta, T6G 2H1, Edmonton, AB, Canada.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Wuest
mesh_terms: D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D005456:Fluorescent Dyes / Q000138:chemical synthesis*; D006801:Humans; D015394:Molecular Structure; D061848:Optical Imaging / Q000379:methods; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D005456:Fluorescent Dyes; D010069:Oxadiazoles; D011743:Pyrimidines; D051546:Cyclooxygenase 2