Abstract
In this work six PBN-related indanonitrones 1-6 have been designed, synthesized, and their neuroprotection capacity tested in vitro, under OGD conditions, in SH-SY5Y human neuroblastoma cell cultures. As a result, we have identified indanonitrones 1, 3 and 4 (EC50 = 6.64 ± 0.28 μM) as the most neuroprotective agents, and in particular, among them, indanonitrone 4 was also the most potent and balanced nitrone, showing antioxidant activity in three experiments [LOX (100 μM), APPH (51%), DPPH (36.5%)], being clearly more potent antioxidant agent than nitrone PBN. Consequently, we have identified (Z)-5-hydroxy-N-methyl-2,3-dihydro-1H-inden-1-imine oxide (4) as a hit-molecule for further investigation.
Keywords:
Antioxidant; Indanonitrones; Lipid peroxidation; Lipoxygenase inhibitors; Neuroprotection; PBN; Synthesis.
Copyright © 2019 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amidines / antagonists & inhibitors
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Amidines / pharmacology
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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / pharmacology*
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Biphenyl Compounds / antagonists & inhibitors
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cyclic N-Oxides / chemistry
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Cyclic N-Oxides / pharmacology*
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Dose-Response Relationship, Drug
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Humans
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Indans / chemical synthesis
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Indans / chemistry
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Indans / pharmacology*
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Lipid Peroxidation / drug effects
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Molecular Structure
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Neuroprotective Agents / chemical synthesis
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology*
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Nitrogen Oxides / chemical synthesis
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Nitrogen Oxides / chemistry
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Nitrogen Oxides / pharmacology*
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Picrates / antagonists & inhibitors
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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Amidines
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Antioxidants
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Biphenyl Compounds
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Cyclic N-Oxides
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Indans
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Neuroprotective Agents
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Nitrogen Oxides
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Picrates
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nitrones
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phenyl-N-tert-butylnitrone
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2,2'-azobis(2-amidinopropane)
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1,1-diphenyl-2-picrylhydrazyl
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indan