Abstract
A novel series of benzylideneindanone derivatives were designed, synthesized, and evaluated as multitarget-directed ligands against Alzheimer's disease. The in vitro studies showed that most of the molecules exhibited a significant ability to inhibit self-induced β-amyloid (Aβ(1-42)) aggregation (10.5-80.1%, 20 μM) and MAO-B activity (IC(50) of 7.5-40.5 μM), to act as potential antioxidants (ORAC-FL value of 2.75-9.37), and to function as metal chelators. In particular, compound 41 had the greatest ability to inhibit Aβ(1-42) aggregation (80.1%), and MAO-B (IC(50) = 7.5 μM) was also an excellent antioxidant and metal chelator. Moreover, it is capable of inhibiting Cu(II)-induced Aβ(1-42) aggregation and disassembling the well-structured Aβ fibrils. These results indicated that compound 41 is an excellent multifunctional agent for the treatment of AD.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / drug therapy*
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Amyloid / chemistry
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Amyloid beta-Peptides / chemistry*
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Antioxidants / chemical synthesis*
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Antioxidants / chemistry
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Benzylidene Compounds / chemical synthesis*
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Benzylidene Compounds / chemistry
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Cations, Divalent
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Chelating Agents / chemical synthesis*
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Chelating Agents / chemistry
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Copper / chemistry
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Humans
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Indans / chemical synthesis*
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Indans / chemistry
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Iron / chemistry
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / chemistry
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Molecular Docking Simulation
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Monoamine Oxidase / chemistry
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Monoamine Oxidase / metabolism
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Monoamine Oxidase Inhibitors / chemical synthesis*
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Monoamine Oxidase Inhibitors / chemistry
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Peptide Fragments / chemistry*
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Recombinant Proteins / chemistry
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Structure-Activity Relationship
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Zinc / chemistry
Substances
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5,6-dihydroxy-2-(4-(methyl(propyl)amino)benzylidene)-2,3-dihydro-1H-inden-1-one
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Amyloid
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Amyloid beta-Peptides
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Antioxidants
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Benzylidene Compounds
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Cations, Divalent
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Chelating Agents
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Indans
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Isoenzymes
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Monoamine Oxidase Inhibitors
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Peptide Fragments
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Recombinant Proteins
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amyloid beta-protein (1-42)
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Copper
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Iron
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Monoamine Oxidase
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Zinc