Abstract
Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.
© 2020 Wiley-VCH GmbH.
MeSH terms
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Animals
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Anti-Arrhythmia Agents / chemical synthesis
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Anti-Arrhythmia Agents / chemistry
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Anti-Arrhythmia Agents / pharmacology*
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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / pharmacology*
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Density Functional Theory
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Fluoresceins / metabolism
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Guinea Pigs
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Humans
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Molecular Structure
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Pyrroles / chemical synthesis
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Pyrroles / chemistry
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Pyrroles / pharmacology*
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Reperfusion Injury / drug therapy*
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Reperfusion Injury / metabolism
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Tumor Cells, Cultured
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Voltage-Gated Sodium Channel Blockers / chemical synthesis
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Voltage-Gated Sodium Channel Blockers / chemistry
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Voltage-Gated Sodium Channel Blockers / pharmacology*
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Voltage-Gated Sodium Channels / metabolism*
Substances
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Anti-Arrhythmia Agents
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Antioxidants
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Fluoresceins
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Pyrroles
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Voltage-Gated Sodium Channel Blockers
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Voltage-Gated Sodium Channels
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2',7'-dichlorodihydrofluorescein
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pyrroline