Abstract
Two multitarget hybrids, derived from an aza-analogue of CGP37157, a mitochondrial Na+ /Ca2+ exchanger antagonist, and lipoic acid were designed in order to combine in a single molecule the antioxidant and Nrf2 induction properties of lipoic acid and the neuroprotective activity of CGP37157. The hybrid derivatives showed Nrf2 induction and radical scavenging properties, leading to a good neuroprotective profile against oxidative stress, together with an interesting antineuroinflammatory activity. The results obtained show differences in activity depending on the configuration of the chiral center of LA.
Keywords:
Nrf2 induction; anti-inflammatory activity; neuroprotection; radical scavenging.
© 2019 Wiley Periodicals, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology
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Antioxidants / chemistry
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Antioxidants / pharmacology*
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Cell Line
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Humans
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Inflammation / drug therapy
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Inflammation / pathology
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Male
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NF-E2-Related Factor 2 / metabolism
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology*
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Oxidative Stress / drug effects
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Rats
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Rats, Sprague-Dawley
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Thiazepines / chemistry
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Thiazepines / pharmacology*
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Thioctic Acid / chemistry
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Thioctic Acid / pharmacology*
Substances
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7-chloro-5-(2-isopropylphenyl)-3,5-dihydro-4,1-benzothiazepin-2-(1H)-one
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Anti-Inflammatory Agents
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Antioxidants
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NF-E2-Related Factor 2
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NFE2L2 protein, human
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Neuroprotective Agents
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Thiazepines
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Thioctic Acid