Abstract
Tacrine and melatonin are well-known drugs with activities as an acetylcholinesterase (AChE) inhibitor and free radical scavenger, respectively. In this work, we report new hybrids of both drugs that display higher in vitro properties than the sum of their parts. As selective inhibitors of human AChE, their IC(50) values range from sub-nanomolar to picomolar. They exhibit a higher oxygen radical absorbance capacity than does melatonin and are predicted to be able to cross the blood-brain barrier to reach their targets in the central nervous system.
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 / chemical synthesis*
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Antioxidants / pharmacology
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Blood-Brain Barrier / metabolism
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Cholinesterase Inhibitors / chemical synthesis*
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Cholinesterase Inhibitors / pharmacology
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Humans
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In Vitro Techniques
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Melatonin / analogs & derivatives*
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Melatonin / chemical synthesis*
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Melatonin / pharmacology
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Permeability
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Structure-Activity Relationship
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Swine
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Tacrine / analogs & derivatives*
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Tacrine / chemical synthesis*
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Tacrine / pharmacology
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Tissue Extracts / metabolism
Substances
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Antioxidants
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Cholinesterase Inhibitors
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Tissue Extracts
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Tacrine
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Acetylcholinesterase
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Melatonin