{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:32:34Z","timestamp":1787877154127,"version":"build-2784847793"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2016,12,21]],"date-time":"2016-12-21T00:00:00Z","timestamp":1482278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dexibuprofen\u2013antioxidant conjugates were synthesized with the aim to reduce its gastrointestinal effects. The esters analogs of dexibuprofen 5a\u2013c were obtained by reacting its \u2013COOH group with chloroacetyl derivatives 3a\u2013c. The in vitro hydrolysis data confirmed that synthesized prodrugs 5a\u2013c were stable in stomach while undergo significant hydrolysis in 80% human plasma and thus release free dexibuprofen. The minimum reversion was observed at pH 1.2 suggesting that prodrugs are less irritating to stomach than dexibuprofen. The anti-inflammatory activity of 5c (p &lt; 0.001) is more significant than the parent dexibuprofen. The prodrug 5c produced maximum inhibition (42.06%) of paw-edema against egg-albumin induced inflammation in mice. Anti-pyretic effects in mice indicated that prodrugs 5a and 5b showed significant inhibition of pyrexia (p &lt; 0.001). The analgesic activity of 5a is more pronounced compared to other synthesized prodrugs. The mean percent inhibition indicated that the prodrug 5a was more active in decreasing the number of writhes induced by acetic acid than standard dexibuprofen. The ulcerogenic activity results assured that synthesized prodrugs produce less gastrointestinal adverse effects than dexibuprofen. The ex vivo antiplatelet aggregation activity results also confirmed that synthesized prodrugs are less irritant to gastrointestinal mucosa than the parent dexibuprofen. Molecular docking analysis showed that the prodrugs 5a\u2013c interacts with the residues present in active binding sites of target protein. The stability of drug\u2013target complexes is verified by molecular dynamic simulation study. It exhibited that synthesized prodrugs formed stable complexes with the COX-2 protein thus support our wet lab results. It is therefore concluded that the synthesized prodrugs have promising pharmacological activities with reduced gastrointestinal adverse effects than the parent drug.<\/jats:p>","DOI":"10.3390\/ijms17122151","type":"journal-article","created":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T04:09:09Z","timestamp":1482466149000},"page":"2151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen\u2013Antioxidant Mutual Prodrugs"],"prefix":"10.3390","volume":"17","author":[{"given":"Zaman","family":"Ashraf","sequence":"first","affiliation":[{"name":"Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Alamgeer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy University of Sargodha, Sargodha 40100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raqiqatur","family":"Rasool","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubashir","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Natural Sciences, Kongju National University, Gongju 314701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haseeb","family":"Ahsan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy University of Sargodha, Sargodha 40100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samina","family":"Afzal","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, BahauddinZakria University, Multan 60800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khurram","family":"Afzal","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, BahauddinZakria University, Multan 60800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1172-8729","authenticated-orcid":false,"given":"Hongsik","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery &amp; Biomedical Engineering, University of Tennessee Health Science Center-Campbell Clinic, Memphis, TN 38104, USA"},{"name":"Research 151, Veterans Affairs Medical Center, Memphis, TN 38104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Natural Sciences, Kongju National University, Gongju 314701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/BF00194342","article-title":"Comparison of the bioavailability of dexibuprofen administered alone or as part of racemic ibuprofen","volume":"48","author":"Gabard","year":"1995","journal-title":"Eur. 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