{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:15:16Z","timestamp":1782450916218,"version":"3.54.5"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistryOpen"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>Aldose reductase (ALDR) is a critical protein involved in the pathogenesis of diabetic complications such as retinopathy, neuropathy, and nephropathy. Due to the activation of inflammatory and cytotoxic pathways under hyperglycemic conditions, ALDR has become an important target for therapeutic development. Currently, available drugs such as epalrestat and ranirestat are suboptimal due to factors such as toxicity and low solubility. In this study, a structure\u2010based approach was used to screen the PubChem database to identify novel ALDR inhibitors with a Tanimoto coefficient greater than 0.8 with the structural frameworks of epalrestat and ranirestat. A systematic virtual screening, including molecular docking, drug\u2010likeness assessment, and molecular dynamics (MD) simulations, revealed two promising candidates, PubChem CIDs: 45110135 and 58643777. These compounds showed higher binding and selectivity toward ALDR than epalrestat and ranirestat in docking studies. MD simulations supported the stability and preferred dynamics of their interactions with ALDR. These findings suggest that compounds CID:45110135 (N\u2010[3\u2010fluoro\u20104\u2010(4\u2010fluoro\u20101,3\u2010dioxoisoindol\u20102\u2010yl)phenyl]pyridine\u20102\u2010carboxamide) and CID:58643777 ([(5Z)\u20104\u2010oxo\u20102\u2010sulfanylidene\u20105\u2010[[3\u2010[3\u2010(trifluoromethyl)phenyl]phenyl]methylidene]\u22121,3\u2010thiazolidin\u20103\u2010yl]propanoic acid) might have the potential to be lead compounds for the development of new drugs for diabetic neuropathy after required validation.<\/jats:p>","DOI":"10.1002\/open.202500110","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T07:01:23Z","timestamp":1755846083000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Structure\u2010Guided Identification and Evaluation of Epalrestat and Ranirestat\u2010Like Compounds Against Aldose Reductase: Therapeutic Management of Diabetic Neuropathy"],"prefix":"10.1002","volume":"14","author":[{"given":"Mohd Shahnawaz","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Biochemistry College of Science King Saud University  Riyadh 11451 Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-1993","authenticated-orcid":false,"given":"Dharmendra Kumar","family":"Yadav","sequence":"additional","affiliation":[{"name":"Gachon Institute of Pharmaceutical Science and Department of Pharmacy College of Pharmacy Gachon University  Incheon 21936 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moyad","family":"Shahwan","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Pharmacy and Health Sciences Ajman University  Ajman UAE"},{"name":"Center of Excellence in Precision Medicine and Digital Health Department of Physiology, Faculty of Dentistry Chulalongkorn University  Bangok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7055-7056","authenticated-orcid":false,"given":"Anas","family":"Shamsi","sequence":"additional","affiliation":[{"name":"Centre of Medical and Bio\u2010Allied Health Sciences Research Ajman University  Ajman 346 UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-019-1212-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13410-022-01165-1"},{"key":"e_1_2_9_4_1","first-page":"88","volume":"44","author":"Darivemula S.","year":"2019","journal-title":"Indian J. 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