Abstract
New tritarget small molecules combining Ca2+ channels blockade, cholinesterase, and H3 receptor inhibition were obtained by multicomponent synthesis. Compound 3p has been identified as a very promising lead, showing good Ca2+ channels blockade activity (IC50 = 21 ± 1 μM), potent affinity against hH3R (Ki = 565 ± 62 nM), a moderate but selective hBuChE inhibition (IC50 = 7.83 ± 0.10 μM), strong antioxidant power (3.6 TE), and ability to restore cognitive impairment induced by lipopolysaccharide.
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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Alzheimer Disease / metabolism
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Animals
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Calcium Channel Blockers / chemistry
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Calcium Channel Blockers / pharmacology*
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Cholinesterase Inhibitors / chemistry
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Cholinesterase Inhibitors / pharmacology*
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Humans
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Memory Disorders / drug therapy
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Memory Disorders / metabolism
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Mice
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Neuroblastoma / drug therapy
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Neuroblastoma / metabolism
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology*
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Receptors, Histamine H3 / chemistry*
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Tumor Cells, Cultured
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Vasodilator Agents / chemistry
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Vasodilator Agents / pharmacology*
Substances
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Calcium Channel Blockers
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Cholinesterase Inhibitors
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Neuroprotective Agents
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Receptors, Histamine H3
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Small Molecule Libraries
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Vasodilator Agents