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dc.contributor.authorTürkeş, Cüneyt
dc.contributor.authorArslan, Mustafa
dc.contributor.authorDemir, Yeliz
dc.contributor.authorCocaj, Liridon
dc.contributor.authorNixha, Arleta Rifati
dc.contributor.authorBeydemir, Şükrü
dc.date.accessioned2023-05-22T13:48:10Z
dc.date.available2023-05-22T13:48:10Z
dc.date.issued2022en_US
dc.identifier.citationTürkeş C, Arslan M, Demir Y, Çoçaj L, Nixha AR, Beydemir Ş. N-substituted phthalazine sulfonamide derivatives as non-classical aldose reductase inhibitors. J Mol Recognit. 2022 Dec;35(12):e2991. doi: 10.1002/jmr.2991. Epub 2022 Sep 26. PMID: 36073557.en_US
dc.identifier.issn0952-3499
dc.identifier.issn1099-1352
dc.identifier.urihttps://doi.org/10.1002/jmr.2991
dc.identifier.urihttps://hdl.handle.net/11552/2980
dc.description.abstractAldose reductase (AR, AKR1B1; EC 1.1.1.21) is an aldo-keto reductase that has been widely investigated as an enzyme crucially involved in the pathogenesis of several chronic complications, including nephropathy, neuropathy, retinopathy, and cataracts associated with diabetes mellitus. Although sulfonamides have been reported to possess many other biological activities, in continuation of our interest in designing and discovering potent inhibitors of AR, herein, we have evaluated the AR inhibitory potential of N-substituted phthalazine sulfonamide derivatives 5a-l. The biological studies revealed that all the derivatives show excellent activity against AR, with KI constants ranging from 67.73 to 495.20 nM. Among these agents, 4-(6-nitro-1,4-dioxo-1,2,3,4-tetrahydrophthalazine-2-carbonyl)benzenesulfonamide (5e) and 1,4-dioxo-3-(4-sulfamoylbenzoyl)-1,2,3,4-tetrahydrophthalazine-6-carboxylic acid (5f) showed prominent inhibitory activity with KI values of 67.73 and 148.20 nM, respectively, vs AR and were found to be more potent than epalrestat (KI = 852.50 nM), the only AR inhibitor currently used in the therapy. Moreover, molecular docking studies were also performed to rationalize binding site interactions of these sulfonamides (5a-l) with the target enzyme AR. According to ADME-Tox, predicts were also determined that these derivatives be ARIs displaying suitable drug-like properties. The sulfonamides identified in this study may be used to develop lead therapeutic agents inhibiting diabetic complications.en_US
dc.description.sponsorshipBu yayın "Research Fund of Erzincan Binali Yldrm University, FBA-2017-501", "Research Fund of Sakarya University, 2016-02-04-018" ve "Anadolu University, 2102S003" tarafından desteklenmiştir.en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.identifier.doi10.1002/jmr.2991en_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAldose Reductaseen_US
dc.subjectIn Silico Studyen_US
dc.subjectPolyol Pathwayen_US
dc.titleN-substituted phthalazine sulfonamide derivatives as non-classical aldose reductase inhibitorsen_US
dc.typearticleen_US
dc.relation.ispartofJournal of Molecular Recognitionen_US
dc.departmentRektörlük, Rektören_US
dc.authorid0000-0003-3667-6902en_US
dc.identifier.volume35en_US
dc.identifier.issue12en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.relation.indexPubMeden_US
dc.relation.indexScopusen_US
dc.relation.indexWoSen_US
dc.relation.indexWoS - Science Citation Index Expandeden_US
dc.contributor.institutionauthorBeydemir, Şükrü
dc.description.wospublicationidWOS:000859573400001en_US
dc.description.pubmedpublicationidPMID: 36073557en_US
dc.description.wosqualityEarly Accessen_US


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