{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:58:40Z","timestamp":1780657120839,"version":"3.54.1"},"reference-count":84,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG)","doi-asserted-by":"publisher","award":["PI-304\/7-1"],"award-info":[{"award-number":["PI-304\/7-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG)","doi-asserted-by":"publisher","award":["CRC\/TRR 205\/1,2"],"award-info":[{"award-number":["CRC\/TRR 205\/1,2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Collaborative Research Center Transregio 205 \u201cThe Adrenal: Central Relay in Health and Disease\u201d","award":["PI-304\/7-1"],"award-info":[{"award-number":["PI-304\/7-1"]}]},{"name":"Collaborative Research Center Transregio 205 \u201cThe Adrenal: Central Relay in Health and Disease\u201d","award":["CRC\/TRR 205\/1,2"],"award-info":[{"award-number":["CRC\/TRR 205\/1,2"]}]},{"name":"Paradifference Foundation","award":["PI-304\/7-1"],"award-info":[{"award-number":["PI-304\/7-1"]}]},{"name":"Paradifference Foundation","award":["CRC\/TRR 205\/1,2"],"award-info":[{"award-number":["CRC\/TRR 205\/1,2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>COX-2 can be considered as a clinically relevant molecular target for adjuvant, in particular radiosensitizing treatments. In this regard, using selective COX-2 inhibitors, e.g., in combination with radiotherapy or endoradiotherapy, represents an interesting treatment option. Based on our own findings that nitric oxide (NO)-releasing and celecoxib-derived COX-2 inhibitors (COXIBs) showed promising radiosensitizing effects in vitro, we herein present the development of a series of eight novel NO-COXIBs differing in the peripheral substitution pattern and their chemical and in vitro characterization. COX-1 and COX-2 inhibition potency was found to be comparable to the lead NO-COXIBs, and NO-releasing properties were demonstrated to be mainly influenced by the substituent in 4-position of the pyrazole (Cl vs. H). Introduction of the N-propionamide at the sulfamoyl residue as a potential prodrug strategy lowered lipophilicity markedly and abolished COX inhibition while NO-releasing properties were not markedly influenced. NO-COXIBs were tested in vitro for a combination with single-dose external X-ray irradiation as well as [177Lu]LuCl3 treatment in HIF2\u03b1-positive mouse pheochromocytoma (MPC-HIF2a) tumor spheroids. When applied directly before X-ray irradiation or 177Lu treatment, NO-COXIBs showed radioprotective effects, as did celecoxib, which was used as a control. Radiosensitizing effects were observed when applied shortly after X-ray irradiation. Overall, the NO-COXIBs were found to be more radioprotective compared with celecoxib, which does not warrant further preclinical studies with the NO-COXIBs for the treatment of pheochromocytoma. However, evaluation as radioprotective agents for healthy tissues could be considered for the NO-COXIBs developed here, especially when used directly before irradiation.<\/jats:p>","DOI":"10.3390\/molecules27196587","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T23:31:43Z","timestamp":1665358303000},"page":"6587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Exploring Nitric Oxide (NO)-Releasing Celecoxib Derivatives as Modulators of Radioresponse in Pheochromocytoma Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Florian","family":"Brandt","sequence":"first","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"},{"name":"Faculty of Chemistry and Food Chemistry, School of Science, Technische Universit\u00e4t Dresden, Mommsenstrasse 4, 01062 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6104-6676","authenticated-orcid":false,"given":"Martin","family":"Ullrich","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Seifert","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"},{"name":"Faculty of Chemistry and Food Chemistry, School of Science, Technische Universit\u00e4t Dresden, Mommsenstrasse 4, 01062 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5032-5095","authenticated-orcid":false,"given":"Cathleen","family":"Haase-Kohn","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-2477","authenticated-orcid":false,"given":"Susan","family":"Richter","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the Technische Universit\u00e4t Dresden, Fetscherstra\u00dfe 74, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4107-3455","authenticated-orcid":false,"given":"Torsten","family":"Kniess","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1610-1493","authenticated-orcid":false,"given":"Jens","family":"Pietzsch","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"},{"name":"Faculty of Chemistry and Food Chemistry, School of Science, Technische Universit\u00e4t Dresden, Mommsenstrasse 4, 01062 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4916-3794","authenticated-orcid":false,"given":"Markus","family":"Laube","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0140-6736(05)67139-5","article-title":"Phaeochromocytoma","volume":"366","author":"Lenders","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/j.1600-0463.2004.apm1120901.x","article-title":"Malignancy in Pheochromocytomas","volume":"112","author":"Salmenkivi","year":"2004","journal-title":"Apmis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.bbrc.2007.05.038","article-title":"The Mechanism of Action of Nitric Oxide-Donating Aspirin","volume":"358","author":"Kashfi","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1002\/cmdc.201600086","article-title":"A Series of COX-2 Inhibitors Endowed with NO-Releasing Properties: Synthesis, Biological Evaluation, and Docking Analysis","volume":"11","author":"Consalvi","year":"2016","journal-title":"Chemmedchem"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"650","DOI":"10.7150\/thno.14479","article-title":"Multimodal Somatostatin Receptor Theranostics Using [(64)Cu]Cu-\/[(177)Lu]Lu-DOTA-(Tyr(3))octreotate and AN-238 in a Mouse Pheochromocytoma Model","volume":"6","author":"Ullrich","year":"2016","journal-title":"Theranostics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1210\/jc.2017-00816","article-title":"Efficacy of Peptide Receptor Radionuclide Therapy for Functional Metastatic Paraganglioma and Pheochromocytoma","volume":"102","author":"Kong","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"T135","DOI":"10.1530\/ERC-15-0175","article-title":"15 YEARS OF PARAGANGLIOMA: Imaging and Imaging-Based Treatment of Pheochromocytoma and Paraganglioma","volume":"22","author":"Castinetti","year":"2015","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1530\/ERC-18-0136","article-title":"Strain-Specific Metastatic Phenotypes in Pheochromocytoma Allograft Mice","volume":"25","author":"Ullrich","year":"2018","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ullrich, M., Richter, S., Seifert, V., Hauser, S., Calsina, B., Mart\u00ednez-Montes, \u00c1.M., ter Laak, M., Ziegler, C.G., Timmers, H., and Eisenhofer, G. (2019). Targeting Cyclooxygenase-2 in Pheochromocytoma and Paraganglioma: Focus on Genetic Background. Cancers, 11.","DOI":"10.3390\/cancers11060743"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1124\/pr.56.3.3","article-title":"Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition","volume":"56","author":"Simmons","year":"2004","journal-title":"Pharm. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1007\/s00726-012-1409-5","article-title":"Protein and Non\u2013Protein Biomarkers in Melanoma: A Critical Update","volume":"43","author":"Tandler","year":"2012","journal-title":"Amino Acids"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Haase-Kohn, C., Laube, M., Donat, C.K., Belter, B., and Pietzsch, J. (2022). CRISPR\/Cas9 Mediated Knockout of Cyclooxygenase-2 Gene Inhibits Invasiveness in A2058 Melanoma Cells. Cells, 11.","DOI":"10.3390\/cells11040749"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2174\/1874467211666180219102520","article-title":"COX-2 in Radiotherapy: A Potential Target for Radioprotection and Radiosensitization","volume":"11","author":"Cheki","year":"2018","journal-title":"Curr. Mol. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1136\/gut.2004.047100","article-title":"Prostaglandins and Cancer","volume":"55","author":"Wang","year":"2006","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.coph.2009.06.020","article-title":"Inflammation and Cancer: How friendly is the relationship for cancer patients?","volume":"9","author":"Aggarwal","year":"2009","journal-title":"Curr. Opin. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.6023\/cjoc202007073","article-title":"Synthesis and Anti\u2013proliferative Activity of Indole-2-Amide Derivatives as Cyclooxygenase-2\/5-lipoxygenase (COX-2\/5-LOX) Dual Inhibitors","volume":"41","author":"Qian","year":"2021","journal-title":"Chin. J. Org. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ejmech.2015.11.013","article-title":"Discovery of Novel Hybrids of Diaryl-1,2,4-Triazoles and Caffeic Acid as Dual Inhibitors of Cyclooxygenase-2 and 5-Lipoxygenase for Cancer Therapy","volume":"108","author":"Cai","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S505","DOI":"10.1016\/S0016-5085(14)61825-4","article-title":"Hydrogen Sulfide (H2S)-Releasing Derivative of Naproxen Atb-346 Protects the Gastric Mucosa Compromised by Stress. A Comparative Study With Naproxen and Cyclooxygenase (COX)-2 Inhibitor","volume":"146","author":"Magierowski","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1039\/C4MD00392F","article-title":"Synthesis, 3D Pharmacophore, QSAR and Docking Studies of Novel Quinazoline Derivatives with Nitric Oxide Release Moiety as Preferential COX-2 Inhibitors","volume":"6","author":"Farag","year":"2015","journal-title":"MedChemComm"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.bmcl.2010.01.014","article-title":"Celecoxib Analogs Possessing a N-(4-nitrooxybutyl)Piperidin-4-yl or N-(4-nitrooxybutyl)-1,2,3,6-Tetrahydropyridin-4-yl nitric Oxide Donor Moiety: Synthesis, Biological Evaluation and Nitric oxide Release Studies","volume":"20","author":"Chowdhury","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1021\/jm301370e","article-title":"Novel Analgesic\/Anti-Inflammatory Agents: 1,5-Diarylpyrrole Nitrooxyalkyl Ethers and Related Compounds as Cyclooxygenase-2 Inhibiting Nitric Oxide Donors","volume":"56","author":"Anzini","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"594","DOI":"10.2174\/1570180811310070006","article-title":"Synthesis of 1,5-Diarylpyrazoles as Potential COX-2 Inhibitors with Nitric Oxide Releasing Ability","volume":"10","author":"Rao","year":"2013","journal-title":"Lett. Drug. Des. Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e17281","DOI":"10.1590\/s2175-97902018000417281","article-title":"Design, Synthesis, Biological Evaluation, and Nitric-Oxide Release Studies of a Novel Series of Celecoxib Prodrugs Possessing a Nitric-Oxide Donor Moiety","volume":"54","author":"Soliman","year":"2018","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1016\/j.ejmech.2008.07.008","article-title":"Synthesis and investigation of anti-inflammatory activity and gastric ulcerogenicity of novel nitric oxide-donating pyrazoline derivatives","volume":"44","author":"Shoman","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105806","DOI":"10.1016\/j.bioorg.2022.105806","article-title":"Trimethoxyphenyl Containing Compounds: Synthesis, Biological Evaluation, Nitric Oxide Release, Modeling, Histochemical and Histopathological studies","volume":"124","author":"Abdelall","year":"2022","journal-title":"Bioorg. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111678","DOI":"10.1016\/j.biopha.2021.111678","article-title":"New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3-Thiazolidine-4-one Scaffold: Design, Synthesis, In Silico and In Vitro Studies","volume":"139","author":"Sava","year":"2021","journal-title":"Biomed. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sava, A., Buron, F., Routier, S., Panainte, A., Bibire, N., Constantin, S.M., Lupascu, F.G., Focsa, A.V., and Profire, L. (2021). Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-oxadiazole-2-thiol Scaffold. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137079"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1080\/14756366.2021.1956912","article-title":"Design and Synthesis of Novel Quinazolinones Conjugated Ibuprofen, Indole Acetamide, or Thioacetohydrazide as Selective COX-2 Inhibitors: Anti-Inflammatory, Analgesic and Anticancer Activities","volume":"36","author":"Sakr","year":"2021","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103752","DOI":"10.1016\/j.bioorg.2020.103752","article-title":"New 1,2,4-Triazole\/Pyrazole Hybrids Linked to Oxime Moiety as Nitric Oxide Donor Celecoxib Analogs: Synthesis, Cyclooxygenase Inhibition Anti-Inflammatory, Ulcerogenicity, Anti-Proliferative Activities, Apoptosis, Molecular Modeling and Nitric Oxide Release Studies","volume":"98","author":"Fadaly","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/0092-8674(94)90266-6","article-title":"Nitric Oxide Synthases: Roles, Tolls, and Controls","volume":"78","author":"Nathan","year":"1994","journal-title":"Cell"},{"key":"ref_31","first-page":"109","article-title":"Nitric oxide: Physiology, Pathophysiology, and Pharmacology","volume":"43","author":"Moncada","year":"1991","journal-title":"Pharm. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev.med.48.1.489","article-title":"Nitric Oxide Synthase: Role in the Genesis of Vascular Disease","volume":"48","author":"John","year":"1997","journal-title":"Annu. Rev. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ddstr.2006.09.004","article-title":"Nitric-Oxide Based Nonsteroidal Anti-Inflammatory Agents","volume":"3","author":"Ongini","year":"2006","journal-title":"Drug. Discov. Today Strat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0014-2999(92)90824-N","article-title":"Nitric Oxide Donors Increase Mucus Gel Thickness in Rat Stomach","volume":"223","author":"Brown","year":"1992","journal-title":"Eur. J. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R3","DOI":"10.1016\/0014-2999(95)00399-6","article-title":"Transdermal Nitroglycerin Prevents Nonsteroidal Anti-Inflammatory Drug Gastropathy","volume":"281","author":"Barrachina","year":"1995","journal-title":"Eur. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1056\/NEJM200009213431202","article-title":"Nitrovasodilators, Low-Dose Aspirin, Other Nonsteroidal Antiinflammatory Drugs, and the Risk Of Upper Gastrointestinal Bleeding","volume":"343","author":"Lanas","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"FSO44","DOI":"10.4155\/fso.15.44","article-title":"Nitric Oxide for Cancer Therapy","volume":"1","author":"Huerta","year":"2015","journal-title":"Future Sci. OA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1136\/gut.52.11.1537","article-title":"Gastrointestinal Safety ff AZD3582, a Cyclooxygenase Inhibiting Nitric Oxide Donator: Proof of Concept Study in Humans","volume":"52","author":"Hawkey","year":"2003","journal-title":"Gut"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1517\/14712590902926071","article-title":"Naproxcinod, a New Cyclooxygenase-Inhibiting Nitric Oxide Donator (CINOD)","volume":"9","author":"Geusens","year":"2009","journal-title":"Expert Opin. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1021\/jm0108799","article-title":"A New Class of Ibuprofen Derivatives with Reduced Gastrotoxicity","volume":"44","author":"Lolli","year":"2001","journal-title":"J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/cmdc.201100393","article-title":"Rofecoxib Analogues Possessing a Nitric Oxide Donor Sulfohydroxamic Acid (SO2NHOH) Cyclooxygenase-2 Pharmacophore: Synthesis, Molecular Modeling, and Biological Evaluation as Anti-inflammatory Agents","volume":"7","author":"Bhardwaj","year":"2012","journal-title":"ChemMedChem"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1039\/c005066k","article-title":"Acyclic Triaryl Olefins Possessing a Sulfohydroxamic Acid Pharmacophore: Synthesis, Nitric Oxide\/Nitroxyl Release, Cyclooxygenase Inhibition, and Anti-Inflammatory Studies","volume":"8","author":"Huang","year":"2010","journal-title":"Org. Biomol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1007\/s005350050178","article-title":"Nitric Oxide: A Regulator of Mucosal Defense and Injury","volume":"33","author":"Elliott","year":"1998","journal-title":"J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.bmc.2013.12.008","article-title":"Enhancing the Pharmacodynamic Profile of a Class of Selective Cox-2 Inhibiting Nitric Oxide Donors","volume":"22","author":"Biava","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.ejmech.2018.08.048","article-title":"Design, Synthesis And Biological Evaluation of Novel Ferrocene-Pyrazole Derivatives Containing Nitric Oxide Donors as COX-2 Inhibitors for Cancer Therapy","volume":"157","author":"Ren","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_46","first-page":"5","article-title":"Ionizing Radiation Induced Nitric Oxide Signaling","volume":"1","author":"Rabender","year":"2014","journal-title":"Austin J. Nucl. Med. Radiother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0027-5107(99)00006-8","article-title":"The Chemistry of DNA Damage From Nitric Oxide and Peroxynitrite","volume":"424","author":"Burney","year":"1999","journal-title":"Mutat. Res.-Fund. Mol. M"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.freeradbiomed.2013.01.014","article-title":"Modification of DNA damage mechanisms by nitric oxide during ionizing radiation","volume":"58","author":"Folkes","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1016\/j.bmcl.2015.05.059","article-title":"Novel (Pyrazolyl)Benzenesulfonamides with a Nitric Oxide-Releasing Moiety as Selective Cyclooxygenase-2 Inhibitors","volume":"25","author":"Bechmann","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_50","first-page":"1010","article-title":"Nitric Oxide-Releasing Selective Cyclooxygenase-2 Inhibitors as Promising Radiosensitizers in Melanoma Cells In Vitro: Supplemental Information","volume":"1","author":"Pietzsch","year":"2018","journal-title":"Ann. Radiat. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/00397910701750185","article-title":"Facile Synthesis ofN\u2013Acylsulfonamide in the Presence of Silica Chloride (SiO2-Cl) both under Heterogeneous and Solvent-Free Conditions","volume":"38","author":"Dabagh","year":"2008","journal-title":"Synth. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s00044-020-02528-1","article-title":"Selective Cyclooxygenase-2 Inhibitors: A Review of Recent Chemical Scaffolds with Promising Anti-Inflammatory and COX-2 Inhibitory Activities","volume":"29","author":"Mohsin","year":"2020","journal-title":"Med. Chem. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"103007","DOI":"10.1016\/j.bioorg.2019.103007","article-title":"Recent Advancement in the Discovery and Development of COX-2 Inhibitors: Insight Into Biological Activities and SAR Studies (2008\u20132019)","volume":"89","author":"Sharma","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1039\/C6MD00569A","article-title":"Structure\u2013Activity Relationships for the Synthesis of Selective Cyclooxygenase 2 Inhibitors: An Overview (2009\u20132016)","volume":"8","author":"Carullo","year":"2017","journal-title":"MedChemComm"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Laube, M., Gassner, C., Kniess, T., and Pietzsch, J. (2019). Synthesis and Cyclooxygenase Inhibition of Sulfonamide-Substituted (Dihydro)Pyrrolo[3,2,1-hi]indoles and Their Potential Prodrugs. Molecules, 24.","DOI":"10.3390\/molecules24203807"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1021\/jm000069h","article-title":"N-[[(5-Methyl-3-Phenylisoxazol-4-Yl)-Phenyl]Sulfonyl]Propanamide, Sodium Salt, Parecoxib Sodium: A Potent and Selective Inhibitor of COX-2 for Parenteral Administration","volume":"43","author":"Talley","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ijpharm.2011.06.013","article-title":"Chemical and In Vitro Enzymatic Stability of Newly Synthesized Celecoxib Lipophilic and Hydrophilic Amides","volume":"416","author":"Qandil","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0021-9673(02)00064-X","article-title":"Method for Measuring the Logarithm ff the Octanol-Water Partition Coefficient by Using Short Octadecyl-Poly(Vinyl Alcohol) High-Performance Liquid Chromatography Columns","volume":"952","author":"Donovan","year":"2002","journal-title":"J. Chromatogr. A"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Seifert, V., Richter, S., Bechmann, N., Bachmann, M., Ziegler, C.G., Pietzsch, J., and Ullrich, M. (2021). HIF2alpha-Associated Pseudohypoxia Promotes Radioresistance In Pheochromocytoma: Insights from 3D Models. Cancers, 13.","DOI":"10.3390\/cancers13030385"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/carcin\/bgs313","article-title":"Hypoxia-Inducible Factor-2\u03b1 Is Essential in Activating The COX2\/Mpges-1\/PGE 2 Signaling Axis in Colon Cancer","volume":"34","author":"Xue","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12032-014-0419-4","article-title":"Hypoxia Promotes 786-O Cells Invasiveness and Resistance to Sorafenib Via HIF-2\u03b1\/COX-2","volume":"32","author":"Zhao","year":"2015","journal-title":"Med. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Gudkov, S.V., Shilyagina, N.Y., Vodeneev, V.A., and Zvyagin, A.V. (2016). Targeted Radionuclide Therapy of Human Tumors. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010033"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.3390\/cancers3043838","article-title":"Targeted Radionuclide Therapy","volume":"3","author":"Ersahin","year":"2011","journal-title":"Cancers"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1159\/000499497","article-title":"Peptide Receptor Radionuclide Therapy as a Novel Treatment for Metastatic and Invasive Phaeochromocytoma and Paraganglioma","volume":"109","author":"Mak","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4351","DOI":"10.3390\/ijms13044351","article-title":"Ultraviolet C Irradiation Induces Different Expression of Cyclooxygenase 2 In NIH 3T3 Cells and A431 Cells: The Roles of COX-2 Are Different in Various Cell Lines","volume":"13","author":"Tai","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"260","DOI":"10.3389\/fonc.2015.00260","article-title":"DNA Damage Response Proteins and Oxygen Modulate Prostaglandin E2 Growth Factor Release in Response to Low and High LET Ionizing Radiation","volume":"5","author":"Allen","year":"2015","journal-title":"Front. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1093\/neuonc\/not062","article-title":"Celecoxib Enhances Radiosensitivity of Hypoxic Glioblastoma Cells Through Endoplasmic Reticulum Stress","volume":"15","author":"Suzuki","year":"2013","journal-title":"Neuro. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1159\/000358713","article-title":"Celecoxib Enhances Radiosensitivity Via Induction of G(2)-M Phase Arrest and Apoptosis in Nasopharyngeal Carcinoma","volume":"33","author":"Zhang","year":"2014","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"697227","DOI":"10.3389\/fonc.2021.697227","article-title":"Celecoxib Blocks Vasculogenic Mimicry via an Off-Target Effect to Radiosensitize Lung Cancer Cells: An Experimental Study","volume":"11","author":"Niu","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_70","first-page":"1088","article-title":"Celecoxib Enhances the Radiosensitivity of HCT116 Cells in a COX-2 Independent Manner By Up-Regulating BCCIP","volume":"9","author":"Xu","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"82","DOI":"10.4103\/1735-5362.199051","article-title":"Celecoxib Mitigates Genotoxicity Induced by Ionizing Radiation in Human Blood Lymphocytes","volume":"12","author":"Hosseinimehr","year":"2017","journal-title":"Res. Pharm. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Laube, M., Kniess, T., and Pietzsch, J. (2016). Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy\u2014A Hypothesis-Driven Review. Antioxidants, 5.","DOI":"10.3390\/antiox5020014"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2174\/1574885514666191119124739","article-title":"Celecoxib A Selective COX-2 Inhibitor Mitigates Fibrosis but not Pneumonitis Following Lung Irradiation: A Histopathological Study","volume":"15","author":"Azmoonfar","year":"2020","journal-title":"Curr. Drug."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.oraloncology.2014.08.001","article-title":"Randomized Double-Blind Placebo-Controlled Trial of Celecoxib for Oral Mucositis in Patients Receiving Radiation Therapy for Head and Neck Cancer","volume":"50","author":"Lalla","year":"2014","journal-title":"Oral. Oncol."},{"key":"ref_75","first-page":"260","article-title":"Effect of Celecoxib on Inhibiting Tumor Repopulation During Radiotherapy in Human Fadu Squamous Cell Carcinoma","volume":"18","author":"Yang","year":"2014","journal-title":"Contemp. Oncol."},{"key":"ref_76","first-page":"615","article-title":"Protective Effects ff 2,3-Diaryl-Substituted Indole-Based Cyclooxygenase-2 Inhibitors on Oxidative Modification of Human Low Density Lipoproteins In Vitro","volume":"61","author":"Pietzsch","year":"2015","journal-title":"Clin. Hemor. Microcirc."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0167-8140(89)90143-6","article-title":"Review of Repair Kinetics for DNA Damage Induced in Eukaryotic Cells In Vitro By Ionizing Radiation","volume":"14","year":"1989","journal-title":"Radiother. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.drudis.2007.07.017","article-title":"Trends in the Development of Radioprotective Agents","volume":"12","author":"Hosseinimehr","year":"2007","journal-title":"Drug. Discov. Today"},{"key":"ref_79","first-page":"2431","article-title":"Dry Column Vacuum Chromatography","volume":"2001","author":"Pedersen","year":"2001","journal-title":"Synthesis"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1158\/1940-6207.CAPR-11-0120","article-title":"Fluorinated Cyclooxygenase-2 Inhibitors as Agents in PET Imaging of Inflammation and Cancer","volume":"4","author":"Uddin","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5812","DOI":"10.1002\/slct.201601618","article-title":"Development of a 18F-labeled Diaryl-Substituted Dihydropyrrolo[3,2,1-hi]indole as Potential Probe for Functional Imaging of Cyclooxygenase-2\u2009with PET","volume":"1","author":"Gassner","year":"2016","journal-title":"ChemistrySelect"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1002\/jps.10494","article-title":"Fast Gradient HPLC Method to Determine Compounds Binding to Human Serum Albumin. Relationships with Octanol\/Water and Immobilized Artificial Membrane Lipophilicity","volume":"92","author":"Valko","year":"2003","journal-title":"J. Pharm. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3233\/JCB-199005","article-title":"Fluorescent Mouse Pheochromocytoma Spheroids Expressing Hypoxia-Inducible Factor 2 Alpha: Morphologic and Radiopharmacologic Characterization","volume":"5","author":"Seifert","year":"2019","journal-title":"J. Cell. Biotechnol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3233\/CH-199102","article-title":"Adjuvant Drug-Assisted Bone Healing: Part I \u2013 Modulation of Inflammation","volume":"73","author":"Rothe","year":"2019","journal-title":"Clin. Hemorheol. Microcirc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6587\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:46:36Z","timestamp":1760143596000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6587"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,5]]},"references-count":84,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27196587"],"URL":"https:\/\/doi.org\/10.3390\/molecules27196587","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,5]]}}}