{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:54:42Z","timestamp":1790358882513,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The development of new anti-inflammatory agents with improved safety and efficacy remains a major therapeutic challenge, particularly in light of the adverse effects associated with conventional nonsteroidal anti-inflammatory drugs. In this study, a series of new flavone derivatives were synthesized and evaluated for their inhibitory activities against Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), and 5-Lipooxygenase (5-LOX) through combined in vitro and in silico approaches. Biological screening demonstrated that several derivatives exhibited moderate to strong inhibitory activity across the three enzymes, with IC50 values ranging from 35.67 \u00b1 2.92 to 1137.44 \u00b1 371.05\u00b5M. Among these, compounds 5a and 5b emerged as the most promising dual COX-2\/5-LOX inhibitors, displaying potent activity toward both targets while maintaining limited COX-1 inhibition, as reflected by their favorable selectivity indices (SI = 2.09 and 5.21, respectively). Molecular docking studies supported the experimental findings, revealing favorable binding affinities of compounds 5a and 5b within the COX-2 active site (PDB: 1CX2), while the flavone\u2013tetrazole hybrid 6b exhibited the highest binding affinity toward the 5-LOX active site (PDB: 6N2W), consistent with its notable inhibitory activity. In silico ADME and toxicity predictions further suggested that the selected derivatives (4a-b, 5a-b, and 6a-b) possess acceptable physiochemical properties, low predicted toxicity, and favorable drug-likeness. Overall, this study identifies flavone-based scaffolds as a promising early-stage lead for the development of dual COX-2\/5-LOX inhibitors and provides a rational basis for the design of safer anti-inflammatory agents.<\/jats:p>","DOI":"10.3390\/cimb48030243","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:33:02Z","timestamp":1772101982000},"page":"243","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Design, Synthesis, and In Vitro Enzymatic Evaluation of Novel Flavone Derivatives as Dual COX-2\/5-LOX Inhibitors Supported by Molecular Docking and ADMET Analysis"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2692-5917","authenticated-orcid":false,"given":"Elmehdi","family":"Fraj","sequence":"first","affiliation":[{"name":"Laboratory of applied Chemistry and Environment, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0314-8484","authenticated-orcid":false,"given":"Amine","family":"Elbouzidi","sequence":"additional","affiliation":[{"name":"Laboratory for Agricultural Production Improvement, Biotechnology, and Environment (LAPABE), Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4094-3807","authenticated-orcid":false,"given":"Haytham","family":"Bouammali","sequence":"additional","affiliation":[{"name":"Laboratory of applied Chemistry and Environment, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4747-5825","authenticated-orcid":false,"given":"Hanane","family":"Jaouani","sequence":"additional","affiliation":[{"name":"Laboratory of applied Chemistry and Environment, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2137-2599","authenticated-orcid":false,"given":"Chaymae","family":"Bourhou","sequence":"additional","affiliation":[{"name":"Laboratory of applied Chemistry and Environment, Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3973-6694","authenticated-orcid":false,"given":"Mohamed","family":"Addi","sequence":"additional","affiliation":[{"name":"Laboratory for Agricultural Production Improvement, Biotechnology, and Environment (LAPABE), Faculty of Sciences, Mohammed First University, Oujda 60000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7487-8770","authenticated-orcid":false,"given":"Susu M.","family":"Zughaier","sequence":"additional","affiliation":[{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. 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