{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:24:14Z","timestamp":1789961054441,"version":"4.0.1"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>New selective COX-2 inhibitors were designed and synthesized by tethering 1,2,3-triazole and benzenesulfonamide pharmacophores to some NSAIDs. Compounds 6b and 6j showed higher in vitro COX-2 selectivity and inhibitory activity (IC50 = 0.04 \u00b5M and S.I. = 329 and 312, respectively) than celecoxib (IC50 = 0.05 \u00b5M and S.I. = 294). Compound 6e revealed equipotent in vitro COX-2 inhibitory activity to celecoxib. Furthermore, 6b and 6j expressed more potent relief of carrageenan-induced paw edema thickness in mice than celecoxib, with ED50 values of 11.74 \u00b5mol\/kg and 13.38 \u00b5mol\/kg vs. 16.24 \u00b5mol\/kg, respectively. Compounds 6b and 6j inhibited the production of PGE2 with a % inhibition of PGE2 production of 90.70% and 86.34%, respectively, exceeding celecoxib\u2019s percentage (78.62%). Moreover, 6b and 6j demonstrated a gastric safety profile comparable to celecoxib. In conclusion, compounds 6b and 6j better achieved the target goal as more potent and selective COX-2 inhibitors than celecoxib in vitro and in vivo.<\/jats:p>","DOI":"10.3390\/ph15101165","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T22:36:44Z","timestamp":1663713404000},"page":"1165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Rational Design and Synthesis of New Selective COX-2 Inhibitors with In Vivo PGE2-Lowering Activity by Tethering Benzenesulfonamide and 1,2,3-Triazole Pharmacophores to Some NSAIDs"],"prefix":"10.3390","volume":"15","author":[{"given":"Nada H.","family":"El-Dershaby","sequence":"first","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour 22516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soad A.","family":"El-Hawash","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaymaa E.","family":"Kassab","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour 22516, Egypt"},{"name":"Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda G.","family":"Daabees","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour 22516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2654-2591","authenticated-orcid":false,"given":"Ahmed E.","family":"Abdel Moneim","sequence":"additional","affiliation":[{"name":"Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-0719","authenticated-orcid":false,"given":"Mostafa M. M.","family":"El-Miligy","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"ref_1","unstructured":"Ghlichloo, I., and Gerriets, V. (2022). Nonsteroidal Anti-inflammatory Drugs (NSAIDs). StatPears [Internet], StatPearls Publishing LLC."},{"key":"ref_2","unstructured":"Agyare, C. (2017). Mechanism of Action of Nonsteroidal Anti-Inflammatory Drugs. 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