{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:09:41Z","timestamp":1785402581929,"version":"3.56.0"},"reference-count":125,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Provost, Amrita Vishwa Vidyapeetham"},{"id":[{"id":"https:\/\/ror.org\/03am10p12","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative disorder with limited effective therapies. In this study, a series of 2-(arylamino)thiazol-4(5H)-one derivatives was synthesized using an efficient microwave-assisted protocol, and evaluated for neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced oxidative stress (OS) in SH-SY5Y neuronal cells and an A\u03b242-expressing Drosophila melanogaster model of AD. Among the synthesized compounds, 3n, 3i, and 3b exhibited low cytotoxicity and significant neuroprotection, as evidenced by increased cell viability, reduced reactive oxygen species (ROS) production, and preserved mitochondrial membrane potential. Notably, compound 3n demonstrated the highest activity and effectively ameliorated A\u03b242-induced behavioral deficits in vivo. Molecular docking studies predicted favorable binding affinity within the acetylcholinesterase (AChE) active site, with the thiazol scaffold and aryl substituents stabilizing ligand binding through \u03c0\u2013\u03c0 stacking and hydrophobic interactions; compound 3n also formed additional hydrogen bonds enhancing its affinity. Consistent with the docking predictions, in vitro AChE inhibition studies demonstrated that compounds 3n, 3i, and 3b inhibited AChE in a concentration-dependent manner. Network pharmacology predicted seven potential core targets implicated in AD pathogenesis and related pathways, including OS, neuroinflammation, and synaptic dysfunction. Furthermore, in silico pharmacokinetic analysis indicated compliance with Lipinski\u2019s and Veber\u2019s rules, supporting favorable drug-like properties. While further experimental validation is essential, these findings highlight 2-(arylamino)thiazol-4(5H)-one derivatives, particularly compound 3n, as promising multifunctional candidates for further preclinical development against AD.<\/jats:p>","DOI":"10.3390\/ijms27156642","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"6642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["2-(Arylamino)thiazol-4(5H)-ones Mitigate Oxidative Stress and Confer Neuroprotection in Cellular and Drosophila Models of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Nikhil Raj","family":"Selvaraj","sequence":"first","affiliation":[{"name":"School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhuvaneshwari S.","family":"V.","sequence":"additional","affiliation":[{"name":"Department of Chemistry, REVA University, Kattigenahalli, Yelahanka, Bangalore 560064, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6477-5465","authenticated-orcid":false,"given":"Durga","family":"Nandan","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"San","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7341-4974","authenticated-orcid":false,"given":"Sudarslal Sadasivan","family":"Nair","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bipin G.","family":"Nair","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvathy","family":"Venugopal","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajaguru","family":"Aradhya","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipin A.","family":"Nair","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2967\/jnmt.125.271788","article-title":"Brain Primer, Part 2: Pathophysiology of Neurodegeneration","volume":"54","author":"Johnson","year":"2026","journal-title":"J. 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