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Classical nonsteroidal anti\u2010inflammatory drugs reduce inflammation primarily by suppressing the cyclooxygenase (COX) pathway. COX enzymes facilitate the conversion of membrane phospholipids into prostaglandins and play functional roles in several metabolic processes, including analgesia, anti\u2010inflammation, apoptosis, angiogenesis, and drug resistance. Moreover, they are also implicated in cancer development, invasion, metastasis, and the differentiation. In this study, eight pyrazolone derivative compounds with potential anti\u2010inflammatory properties were synthesized. Their structures were successfully characterized using\n                    <jats:sup>1<\/jats:sup>\n                    H nuclear magnetic resonance (NMR),\n                    <jats:sup>13<\/jats:sup>\n                    C NMR, infrared spectroscopy (IR), and high\u2010resolution mass spectrometry (HRMS) spectroscopy. Their inhibitory activities againt COX\u20101, COX\u20102, and 5\u2010lipoxygenase were evaluated to determine their anti\u2010inflammatory potential. Epidermal growth factor receptor inhibition assays were performed for the active compounds 7 and 8, while compound 7, the most potent molecule, was further assessed for p38 mitogen\u2010activated protein kinase inhibition. Several compounds exhibited selective cytotoxicity toward cancer cell lines. Notably, compounds 7 and 8 showed no inhibitory activity against COX\u20101 yet demonstrated considerable selectivity toward COX\u20102. Interestingly, some derivatives displaying selective cytotoxic effects were not among the most potent COX\u20102 inhibitors. Overall, the findings indicate that the synthesized pyrazolone derivatives represent promising lead candidates for the development of anti\u2010inflammatory and anticancer agents.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500778","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T08:51:18Z","timestamp":1771577478000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting Inflammatory and Oncogenic Pathways: Cyclooxygenase\u20102, Epidermal Growth Factor Receptor, and p38 Mitogen\u2010Activated Protein Kinase Inhibition by Pyrazolone Derivatives"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1896-2729","authenticated-orcid":false,"given":"Sevde Nur","family":"Biltekin Kaleli","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Microbiology School of Pharmacy Medipol University  Istanbul 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