2026-10-28T02:55:31Zhttps://kostu-rdlopen.rawdatalibrary.net/oai/requestoai:kostu-rdlopen.rawdatalibrary.net:kostu/102472026-10-27T23:53:11Zopenairecom_kostu_10000col_kostu_10001com_kostu_10007col_kostu_10059Multifunctional anti-Alzheimer's agents: Synthesis, biological evaluation, and molecular docking study of new 2-phenoxyacetamide/3-phenoxypropanamide/4-oxobutanamide derivativesShakila, ShakilaKilic, BurcuBardakkaya, MerveAksakal, FatmaSagkan, Rahsan IlikciDogruer, Deniz S.Alzheimer's diseaseCholinesterase inhibitory activityMolecular dockingMulti-target-directed ligandsNeuroprotective effectIn the current study, three series of new compounds were designed and synthesized through hit optimization, based on the hit compound with a structure (E)-N-(4-{[benzyl(methyl)amino]methyl}thiazol-2-yl)-3-(3,4-dimethoxyphenyl)prop‑2-enamide, which was found as a potential multifunctional anti-Alzheimer agent in our previous study. Then, the biological activities of synthesized compounds (4a-c, 13a-b and 15a-c) were evaluated. The results indicated that 4b, a 2-phenoxyacetamide derivative, exhibited good multifunctional activities. Namely, compound 4b displayed better BChE inhibition (BChE IC50 = 2.10 µM) and antioxidant activity (ORAC = 1.18 Trolox equivalents) compared to the hit compound (BChE IC50 = 14.70 µM, ORAC = 0.5 Trolox equivalents). Additionally, 4b was able to chelate all tested biometals and it also exhibited a neuroprotective effect (63 %), comparable to reference ferulic acid (77 %) while maintaining its safety upon PC12 cell line. When it comes to lowering the levels of TNF-α, NO, IL-1β, and IL-6, 4b performed better activity, relative to the other synthesized compounds. Subsequently, in silico studies such as physicochemical properties, density functional theory (DFT) computational approach and molecular docking studies were performed.Elsevier B.V.2024Articlehttps://rdlopen.rawdatalibrary.net/r/kostu/10247https://doi.org/10.1016/j.molstruc.2024.1391060022-2860enJournal of Molecular Structureinfo:eu-repo/semantics/closedAccessinfo:eu-repo/semantics/articlehttps://kostu-rdlopen.rawdatalibrary.net/tr/items/kostu/10247