{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:53:04Z","timestamp":1791355984618,"version":"4.3.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Inducible nitric oxide synthase (iNOS) is a key mediator of inflammatory signaling, and excessive iNOS\u2010derived nitric oxide (NO) contributes to the pathology of multiple chronic inflammatory disorders. Herein, we report the design and synthesis of a focused series of 5\u2010substituted 4\u2010allyl\u20101,2,4\u2010triazole\u20103\u2010thiol derivatives (\n                    <jats:bold>7a\u2013f<\/jats:bold>\n                    ) bearing an acetanilide fragment, targeting suppression of iNOS\u2010driven NO production. In lipopolysaccharide (LPS)\u2010stimulated RAW264.7 macrophages, several analogues attenuated nitrite accumulation, with compound\n                    <jats:bold>7c<\/jats:bold>\n                    emerging as the most active member of the series (\n                    <jats:bold>80%<\/jats:bold>\n                    inhibition at 100\u2009\u03bcM;\n                    <jats:bold>IC\u2085\u2080<\/jats:bold>\n                    \u2009=\u2009\n                    <jats:bold>12.91\u2009\u03bcM<\/jats:bold>\n                    ). Mechanistically,\n                    <jats:bold>7c<\/jats:bold>\n                    downregulated iNOS protein expression in a concentration\u2010dependent manner, consistent with its NO\u2010suppressing phenotype. In vivo, compound\n                    <jats:bold>7c<\/jats:bold>\n                    significantly reduced L\u2010arginine\u2013potentiated carrageenan paw edema, decreased paw nitrite levels, improved histopathological inflammatory features, and displayed lower ulcerogenic liability than indomethacin at the tested conditions. Collectively, these findings identify allyl\u20101,2,4\u2010triazoles as a promising scaffold for developing next\u2010generation anti\u2010inflammatory agents acting through iNOS downregulation.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70320","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:32:16Z","timestamp":1779802336000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of Novel 5\u2010Substituted\u20104\u2010Allyl\u20101,2,4\u2010Triazoles as Potential Nonsteroidal Anti\u2010Inflammatory Agents via Downregulation of iNOS Expression"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9586-2644","authenticated-orcid":false,"given":"Samar H.","family":"Abbas","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy Minia University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa S. A.","family":"Hammad","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Minia University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1423-8151","authenticated-orcid":false,"given":"Dina M. M. H.","family":"El\u2010Kossi","sequence":"additional","affiliation":[{"name":"Physiology Department, Faculty of Veterinary Medicine Minia University El\u2010Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha F. S.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy Minia University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.10.411"},{"key":"e_1_2_9_3_1","volume-title":"Theory and Practice of Histological Techniques","author":"Bancroft J. 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