Abstract
In this work we describe the synthesis and biological evaluation of the tacrine-1,4-dihydropyridine (DHP) hybrids (3-11). These multipotent molecules are the result of the juxtaposition of an acetylcholinesterase inhibitor (AChEI) such as tacrine (1) and a 1,4-DHP such as nimodipine (2). Compounds 3-11 are very selective and potent AChEIs and show an excellent neuroprotective profile and a moderate Ca2+ channel blockade effect. Consequently, these molecules are new potential drugs for the treatment of Alzheimer's disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / chemistry*
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Acetylcholinesterase / metabolism
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Alzheimer Disease / drug therapy
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Animals
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Antioxidants / pharmacology
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Calcium / metabolism
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Calcium Channels / chemistry
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Cell Proliferation / drug effects
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Cells, Cultured
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Dihydropyridines / chemistry*
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Eels / metabolism
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Humans
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Hydrogen Peroxide / pharmacology
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L-Lactate Dehydrogenase / metabolism
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Neuroblastoma / metabolism
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Neuroblastoma / pathology
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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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Structure-Activity Relationship
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Tacrine / chemistry*
Substances
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Antioxidants
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Calcium Channels
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Dihydropyridines
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Neuroprotective Agents
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Tacrine
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1,4-dihydropyridine
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Hydrogen Peroxide
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L-Lactate Dehydrogenase
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Acetylcholinesterase
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Calcium