20.500.12556/RUL-139371 Polyfunctionalized α-phenyl-tert-butyl(benzyl)nitrones multifunctional antioxidants for stroke treatment Nowadays, most stroke patients are treated exclusively with recombinant tissue plasminogen activator, a drug with serious side effects and limited therapeutic window. For this reason, and because of the known effects of oxidative stress on stroke, a more tolerable and efficient therapy for stroke is being sought that focuses on the control and scavenging of highly toxic reactive oxygen species by appropriate small molecules, such as nitrones with antioxidant properties. In this context, herein we report here the synthesis, antioxidant, and neuroprotective properties of twelve novel polyfunctionalized α-phenyl-tert-butyl(benzyl)nitrones. The antioxidant capacity of these nitrones was investigated by various assays, including the inhibition of lipid peroxidation induced by AAPH, hydroxyl radical scavenging assay, ABTS+-decoloration assay, DPPH scavenging assay, and inhibition of soybean lipoxygenase. The inhibitory effect on monoamine oxidases and cholinesterases and inhibition of β-amyloid aggregation were also investigated. As a result, (Z)-N-benzyl-1-(2-(3-(piperidin-1-yl)propoxy)phenyl)methanimine oxide (5) was found to be one of the most potent antioxidants, with high ABTS+ scavenging activity (19%), and potent lipoxygenase inhibitory capacity (IC50 = 10 µM), selectively inhibiting butyrylcholinesterase (IC50 = 3.46 ± 0.27 µM), and exhibited neuroprotective profile against the neurotoxicant okadaic acid in a neuronal damage model. Overall, these results pave the way for the further in-depth analysis of the neuroprotection of nitrone 5 in in vitro and in vivo models of stroke and possibly other neurodegenerative diseases in which oxidative stress is identified as a critical player. butyrylcholinesterase free radical scavengers neuroprotection α-phenyl-tert-butyl(benzyl)nitrones in vitro digestion extractable and bound phenolics antioksidanti butirilholinesteraza lovilci prostih radikalov nevroprotekcija α-fenil-terc-butil(benzil)nitroni oksidativni stres true false true Angleški jezik Slovenski jezik Neznano 2022-09-01 09:41:36 2022-09-01 09:41:41 2022-09-16 04:10:29 0000-00-00 00:00:00 2022 0 0 20 str., art. 1735 Iss. 9 Vol. 11 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2022-08-31 612.015:616.127-005.8 2076-3921 10.3390/antiox11091735 119819011 https://www.mdpi.com/2076-3921/11/9/1735 1 7bf1eec0-29c9-11ed-92af-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=159922 antioxidants-11-01735.pdf antioxidants-11-01735.pdf 1 C64216B59CE76F4B43F6B07297438AE4 9ddd1ef8c84f0635768e4b05c27cf182ef8c449f8ee8a79675a0f95ccf629693 5c65b3ef-29ca-11ed-92af-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=159924 Fakulteta za farmacijo 0 0 0