{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:26:07Z","timestamp":1783110367564,"version":"3.54.6"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Dual cyclooxygenase\u20102\/5\u2010lipoxygenase (COX\u20102\/5\u2010LOX) inhibitors constitute safer alternatives to classical nonsteroidal anti\u2010inflammatory drugs, widely used to effectively manage inflammation. In this article, molecular docking and molecular dynamics simulations guide the synthesis of novel thymol derivatives that interact with both COX\u20102 and 5\u2010LOX active sites. Ligands are designed with the aim of improving thymol bioactivity, selectivity, stability, as well as pharmacokinetic properties. Therefore, \u2013Br, \u2013F, and \u2013CF\n                    <jats:sub>3<\/jats:sub>\n                    inclusion on thymol is here evaluated, screening COX\u20102 and 5\u2010LOX interactions with thymol (\n                    <jats:bold>T<\/jats:bold>\n                    ), 4\u2010fluorothymol (\n                    <jats:bold>FT<\/jats:bold>\n                    ), 4\u2010bromothymol (\n                    <jats:bold>BT<\/jats:bold>\n                    ), isopropyl thymyl succinate (\n                    <jats:bold>T1<\/jats:bold>\n                    ), 1,1,1,3,3,3\u2010hexafluoroisopropyl thymyl succinate (\n                    <jats:bold>T2<\/jats:bold>\n                    ), and 1\u2032,1\u2032,1\u2032,3\u2032,3\u2032,3\u2032\u2010hexafluoroisopropyl 4\u2010(4\u2032\u2019\u2010thymyl)\u20104\u2010oxobutanoate (\n                    <jats:bold>T3<\/jats:bold>\n                    ). Molecular modeling reveals that the estimated ligands can establish favorable interactions with both COX\u20102 and 5\u2010LOX active pockets, highlighting\n                    <jats:bold>T1<\/jats:bold>\n                    <jats:bold>\u2013T3<\/jats:bold>\n                    as the most promising compounds. In\u2009vitro assays identify\n                    <jats:bold>T3<\/jats:bold>\n                    as the most active COX\u20102 inhibitor, while\n                    <jats:bold>T2<\/jats:bold>\n                    results as the most effective ligand for 5\u2010LOX. Interestingly, cavity analysis of the COX\u20102 entry site reveals that\n                    <jats:bold>T3<\/jats:bold>\n                    insertion is favored over\n                    <jats:bold>T1<\/jats:bold>\n                    and\n                    <jats:bold>T2<\/jats:bold>\n                    due to its greater polarity, conferred by the presence of a free phenolic group (OH) able to establish H\u2010bonds with surrounding residues.\n                  <\/jats:p>","DOI":"10.1002\/cbic.202500706","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T06:45:18Z","timestamp":1765781118000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual COX\u20102\/5\u2010LOX Inhibition by Novel Thymol Derivatives: From Molecular Modeling to In Vitro Validation"],"prefix":"10.1002","volume":"27","author":[{"given":"Alice","family":"Romeo","sequence":"first","affiliation":[{"name":"Department of Biology University of Rome Tor Vergata  Via della Ricerca Scientifica 00133 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pezzola","sequence":"additional","affiliation":[{"name":"Department of Chemical Science and Technologies University of Rome Tor Vergata  Via della Ricerca Scientifica 00133 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Valentini","sequence":"additional","affiliation":[{"name":"Department of Chemical Science and Technologies University of Rome Tor Vergata  Via della Ricerca Scientifica 00133 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Iacovelli","sequence":"additional","affiliation":[{"name":"Department of Biology University of Rome Tor Vergata  Via della Ricerca Scientifica 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