Abstract
A major effort in Alzheimer's disease therapeutic development has targeted Aβ and downstream events. We have synthesized a small library of tricyclic pyrone compounds. Their protective action in MC65 cells and inhibition of ACAT along with the upregulation of cholesterol transporter gene were investigated. Five active compounds exhibited potencies in the nanomolar ranges. The multiple effects of the compounds on Aβ and cellular cholesterol pathways could be potential mechanisms underlying the protective effects in vivo.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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ATP Binding Cassette Transporter 1
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism*
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Acetyl-CoA C-Acetyltransferase / antagonists & inhibitors*
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Amyloid beta-Peptides / physiology*
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Cell Death
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Cell Line
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Gene Expression
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Heterocyclic Compounds, 3-Ring / chemical synthesis*
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Heterocyclic Compounds, 3-Ring / chemistry
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Heterocyclic Compounds, 3-Ring / pharmacology
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Humans
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Neurons / cytology
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Neurons / drug effects*
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Pyrones / chemical synthesis*
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Pyrones / chemistry
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Pyrones / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
Substances
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ATP Binding Cassette Transporter 1
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ATP-Binding Cassette Transporters
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Amyloid beta-Peptides
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Heterocyclic Compounds, 3-Ring
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Pyrones
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Acetyl-CoA C-Acetyltransferase