{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T07:10:38Z","timestamp":1778829038418,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010322","name":"Pakistan Academy of Sciences","doi-asserted-by":"publisher","award":["Project No. 111"],"award-info":[{"award-number":["Project No. 111"]}],"id":[{"id":"10.13039\/501100010322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistryOpen"],"published-print":{"date-parts":[[2026,4]]},"abstract":"\n Selected naproxen derivatives were investigated for their antinociceptive effects, using in vitro (COX\u2010I\/COX\u2010II antagonistic effect), in vivo (acetic acid and hot plate assay), and in silico (molecular simulation studies) approaches. The COX inhibition studies revealed that the maximum percent effect exhibited by\n GMO\u2010I\u2010111a<\/jats:bold>\n 96.01 and 92% against COX\u20102 and COX\u20101, respectively, at higher concentrations. The effect at minimum concentration was 81 and 77% against COX\u20101 and COX\u20102, respectively. The COX antagonist effect of\n GMO\u2010I\u20109a<\/jats:bold>\n and\n GMO\u2010I\u201011a<\/jats:bold>\n was also outstanding in the acetic acid assay. All the tested derivatives demonstrated a significant (\n p<\/jats:italic>\n \u2009<\u20090.05) analgesic effect at all concentrations (1.25, 2.5, and 10\u2009mg\/kg). The maximum effect was found against\n GMO\u2010I\u2010135a<\/jats:bold>\n (95%), followed by\n GMO\u2010I\u201011a<\/jats:bold>\n (92%). The central analgesic effect of various derivatives was significant (\n p<\/jats:italic>\n \u2009<\u200900.1).\n GMO\u2010I\u2010111a<\/jats:bold>\n exhibited a significant (\n p<\/jats:italic>\n \u2009<\u200900.1) analgesic effect after 30\u2009min at all the tested doses. The maximum effect at higher doses was shown by compound\n GMO\u2010I\u20109a<\/jats:bold>\n (93%) followed by\n GMO\u2010I\u201011a<\/jats:bold>\n (88%),\n GMO\u2010I\u2010111a<\/jats:bold>\n (84%), and\n GMO\u2010I\u2010135a<\/jats:bold>\n (78%). The latency time of\n GMO\u2010I\u20109a<\/jats:bold>\n and\n GMO\u2010I\u2010135a<\/jats:bold>\n was significantly reversed by naloxone treatment, indicating the central analgesic effect. The molecular simulation studies showed that all the tested compounds had good binding interactions with COX\u20101\/COX\u20102, except\n GMO\u2010I\u20109a<\/jats:bold>\n . In conclusion, the tested naproxen derivatives might have a significant analgesic effect.\n <\/jats:p>","DOI":"10.1002\/open.202500493","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T09:59:48Z","timestamp":1774605588000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Silico, In Vitro, and In Vivo Antinociceptive Potential of\n S<\/i>\n \u2010Naproxen Derivatives"],"prefix":"10.1002","volume":"15","author":[{"family":"Ubaidullah","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Swabi Swabi Khyber Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naveed","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Abdul Wali Khan University Mardan Khyber Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abad","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Swabi Swabi Khyber Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahaf","family":"Ajaj","sequence":"additional","affiliation":[{"name":"College of Engineering Abu Dhabi University Abu Dhabi United Arab Emirates"},{"name":"Research Institute for Sustainable Futures Abu Dhabi University Abu Dhabi United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2429-5491","authenticated-orcid":false,"given":"Abdur","family":"Rauf","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Swabi Anbar Khyber Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umer","family":"Rashid","sequence":"additional","affiliation":[{"name":"Deparment of Pharmacy COMSAT University Abbottabad Abbottabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahad","family":"Hussain","sequence":"additional","affiliation":[{"name":"Deparment of Pharmacy COMSAT University Abbottabad Abbottabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashid","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Swabi Swabi Khyber Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faiza","family":"Seraj","sequence":"additional","affiliation":[{"name":"H. 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Research Institute of Chemistry International Center for chemical and Biological Sciences University of Karachi Karachi Pakistan"},{"name":"Pakistan Academy of Sciences Islamabad Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5063-1236","authenticated-orcid":false,"given":"Marcello","family":"Iriti","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences University of Milan Milan Italy"},{"name":"National Interuniversity Consortium of Materials Science and Technology (INSTM) Firenze Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2001.tb07001.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2007.02.009"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.S0022-0302(94)77234-9"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","unstructured":"C. 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