{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:10:50Z","timestamp":1782796250031,"version":"3.54.5"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,6,22]],"date-time":"2025-06-22T00:00:00Z","timestamp":1750550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009392","name":"Prince Sattam bin Abdulaziz University","doi-asserted-by":"publisher","award":["PSAU\/2024\/03\/31847"],"award-info":[{"award-number":["PSAU\/2024\/03\/31847"]}],"id":[{"id":"10.13039\/100009392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Alcoholism and alcohol misuse are major public health concerns, and chronic alcohol consumption negatively impacts memory and can lead to neurodegeneration and neuroinflammation. Neuroinflammation is a prevalent characteristic of all neurological diseases, induced by oxidative stress and resulting in impaired neuronal function. Thus, targeting neuroinflammation and oxidative stress can be a pivotal mechanism for attenuating memory impairment. In the current study, new isoxazolone derivatives were synthesized, and their synthetic properties were characterized using proton nuclear magnetic resonance (<jats:sup>1<\/jats:sup>H NMR) and Fourier transform infrared (FTIR) spectroscopy. The molecular simulation studies were performed on triggering receptors expressed on myeloid cells\u20101 (TREM\u20101) and nucleotide\u2010binding domain, leucine\u2010rich\u2010containing family, pyrin domain\u2010containing\u20103 (NLRP3). Further, these derivatives were evaluated for neuroprotective potential in an ethanol\u2010induced neuroinflammation model in male albino mice. Our results demonstrated ethanol\u2010induced cognitive deficits, elevated inflammatory markers, ROS and altered endogenous antioxidant enzyme levels. At the same time, treatment with isoxazolone reversed the hyperactivated inflammatory markers, including NLRP3, and modulated the TREM\u20102 expression. Further, the antioxidant and anti\u2010cholinesterase potential of these derivatives was also evaluated using in\u00a0vitro assays. Our results suggested that these derivatives may help reduce neuroinflammation by acting on several stages of the inflammatory process in an ethanol\u2010induced neurodegenerative model.<\/jats:p>","DOI":"10.1111\/1440-1681.70051","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T02:35:54Z","timestamp":1750646154000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis, Characterization, Molecular Dynamic Simulation and Neuroprotective Effects of Synthetic Isoxazolone Derivatives in Ethanol\u2010Induced Neurodegeneration"],"prefix":"10.1111","volume":"52","author":[{"given":"Maria","family":"Awan","sequence":"first","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences, Riphah International University Islamabad  Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Albaqami","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, Prince Sattam bin Abdulaziz University  Al\u2010Kharj Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences, Riphah International University Islamabad  Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqra","family":"Zulfiqar","sequence":"additional","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences, Riphah International University Islamabad  Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najeeb Ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, Prince Sattam bin Abdulaziz University  Al\u2010Kharj Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ayaz","sequence":"additional","affiliation":[{"name":"Swat College of Pharmaceutical Sciences (SCPS)  Gogdara Swat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Faiyaz","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, Prince Sattam bin Abdulaziz University  Al\u2010Kharj Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawad Ali","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, Prince Sattam bin Abdulaziz University  Al\u2010Kharj Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agn079"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.15019"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.02.012"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408363.2011.580567"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.10.015"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11065-007-9038-6"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01214.x"},{"key":"e_1_2_11_9_1","first-page":"1","volume-title":"Translational Neurodegeneration in the Era of Fast Growing International Brain Research","author":"Zheng J. 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