{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:24:53Z","timestamp":1788272693051,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T00:00:00Z","timestamp":1594598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A series of new isoxazolone (<jats:bold>3a<\/jats:bold>\u2013<jats:bold>d<\/jats:bold>) and pyrazolone (<jats:bold>4a<\/jats:bold>\u2013<jats:bold>d<\/jats:bold>) derivatives were synthesized and assessed for their antioxidant and analgesic activity. Among synthesized compounds, <jats:bold>3b<\/jats:bold> and <jats:bold>4b<\/jats:bold> having nitro (NO<jats:sub>2<\/jats:sub>) group show high analgesic activity at a dose of 6 mg\/kg. Analgesic activity was further proceeded to explore the contribution of opioidergic mechanisms in the mediation of analgesic effects. Animals were administered with naloxone, a nonselective opioid inverse agonist, at the dose of 0.5 mg\/kg. The results obtained suggested that the analgesic effects of the synthesized compounds were not reversed by naloxone, specifying that the compounds <jats:bold>3b<\/jats:bold> and <jats:bold>4b<\/jats:bold> do not follow the opioidergic pathway in order to relieve pain in animal models. Further, the binding interactions of compounds <jats:bold>3b<\/jats:bold> and <jats:bold>4b<\/jats:bold> were analyzed by docking them against nonopioid receptors COX\u20101 (3N8X) and COX\u20102 (3LN1). The results demonstrate the analgesic potential of isoxazolone and pyrazolone derivatives, especially compounds <jats:bold>3b<\/jats:bold> and <jats:bold>4b<\/jats:bold> can be considered promising lead molecules for further investigation and development into potent analgesic drugs. In addition, the antioxidant potential of compounds was also found to be related to better analgesic activity, thus providing an insight into the role of oxidative stress in the mediation of analgesia.<\/jats:p>","DOI":"10.1002\/ddr.21711","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T23:51:34Z","timestamp":1594684294000},"page":"893-903","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Investigation of antioxidant and anti\u2010nociceptive potential of isoxazolone, pyrazolone derivatives, and their molecular docking studies"],"prefix":"10.1002","volume":"81","author":[{"given":"Tayyaba","family":"Anwar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Riphah Institute of Pharmaceutical Sciences Riphah International University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0169-0811","authenticated-orcid":false,"given":"Humaira","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Riphah Institute of Pharmaceutical Sciences Riphah International University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Sarwar","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Riphah Institute of Pharmaceutical Sciences Riphah International University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Naureen","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Riphah Institute of Pharmaceutical Sciences Riphah International University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safia","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biological Science Quaid e Azam University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2959-0414","authenticated-orcid":false,"given":"ArifUllah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences Riphah International University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muazzam","family":"Arif","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Riphah Institute of Pharmaceutical Sciences Riphah International University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2007.12.009"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2005.09.059"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-827X(97)00006-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2010.07.003"},{"key":"e_1_2_7_7_1","volume-title":"Molinspiration Cheminformatics","author":"Cheminformatics","year":"2013"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-4939-2269-7_19","volume-title":"Chemical Biology","author":"Dallakyan S.","year":"2015"},{"issue":"1","key":"e_1_2_7_9_1","first-page":"82","article-title":"Pymol: An open\u2010source molecular graphics tool","volume":"40","author":"DeLano W. 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