2026-10-18T23:43:32Zhttps://ebyu-rdlopen.rawdatalibrary.net/oai/request

oai:ebyu-rdlopen.rawdatalibrary.net:ebyu/106562026-10-18T21:13:09Zopenairedrivercom_ebyu_10000col_ebyu_10001

Isovanillin-derived bis-hydrazones as dual cholinesterase and carbonic anhydrase inhibitors: synthesis, enzymatic profiling, and computational insights from molecular docking and dynamicsTürkeş, CüneytYapar, GönülDuran, Hatice EsraLolak, NebihAkocak, SuleymanADMET profilingbis-hydrazone derivativescarbonic anhydrase inhibitioncholinesterase inhibitionIsovanillinmolecular dockingmolecular dynamicsAcetylcholinesteraseBenzaldehydesButyrylcholinesteraseCarbonic Anhydrase ICarbonic Anhydrase IICarbonic Anhydrase InhibitorsCholinesterase InhibitorsHumansHydrazonesMolecular Docking SimulationMolecular Dynamics SimulationMolecular StructureStructure-Activity Relationshipacetazolamidebishydrazone derivativecarbonate dehydratase Icarbonate dehydratase IIcholinesterasehydrazone derivativetacrineunclassified drugbenzaldehyde derivativecarbonate dehydratase inhibitorAims: To develop isovanillin-based bis-hydrazones as multitarget inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I/II (hCA I/II). Materials & methods: Twelve bis-hydrazones (4a–4l) were synthesized in two steps and evaluated by spectrophotometric enzyme assays, Lineweaver–Burk kinetics, molecular docking, MM-GBSA, molecular dynamics simulations, and in silico ADME/Tox profiling. Results: All compounds showed nanomolar inhibition. Compound 4d was the most potent AChE/BChE inhibitor (KI = 10.46 and 3.56 nM), while 4a and 4j led the hCA I/II panel (KI = 3.46 and 16.12 nM). Docking, MM-GBSA, and molecular dynamics supported dual-site cholinesterase engagement and non-zinc, peripherally anchored hCA inhibition. Conclusions: Isovanillin-based bis-hydrazones, particularly 4d, 4a, and 4j, represent promising multitarget leads for cholinergic and hCA-linked disorders. © 2026 Informa UK Limited, trading as Taylor & Francis Group.Taylor and Francis Ltd.2026Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/10656https://doi.org/10.1080/17568919.2026.26176081756-8919enFuture Medicinal Chemistryinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/10656