mannich-bases and Alzheimer-Disease

Based on the multitarget-directed ligands strategy, a series of 3-butyl-6-benzyloxyphthalide Mannich base derivatives were designed, synthesized and identified for Alzheimer's disease (AD). Biological activity studies demonstrated that the designed hybrids showed multitarget activities toward AD. Among them, compound 7d was the most potent agent with excellent inhibitory activities on EeAChE (IC

Topics: Acetylcholinesterase; Alzheimer Disease; Animals; Blood-Brain Barrier; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Drug Discovery; Electrophorus; Humans; Mannich Bases; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neuroprotective Agents; Oxidative Stress; Structure-Activity Relationship

Different Mannich base derivatives have been studied with the aim of addressing the poor aqueous solubility of the recently disclosed 6-phenethyl-2,3,4,5-tetrahydroazepino[4,3-b]indol-1(6H)-one (1), a human butyrylcholinesterase inhibitor (hBChE, IC

Topics: Acetylcholinesterase; Alzheimer Disease; Butyrylcholinesterase; Cell Line, Tumor; Cell Survival; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Humans; Mannich Bases; Models, Molecular; Molecular Structure; Neuroprotective Agents; Prodrugs; Solubility; Structure-Activity Relationship; Water

To discover novel multifunctional agents for the treatment of Alzheimer's disease, a series of 3-benzylidene/benzylphthalide Mannich base derivatives were designed, synthesized and evaluated. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound (Z)-13c raised particular interest because of its excellent multifunctional bioactivities. It displayed excellent EeAChE and HuAChE inhibition (IC

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Benzofurans; Benzylidene Compounds; Blood-Brain Barrier; Butyrylcholinesterase; Cholinesterase Inhibitors; Copper; Dose-Response Relationship, Drug; Electrophorus; Female; Humans; Male; Mannich Bases; Mice; Mice, Inbred Strains; Models, Molecular; Molecular Structure; Neuroprotective Agents; PC12 Cells; Peptide Fragments; Protein Aggregates; Rats; Structure-Activity Relationship

The complex pathogenesis of Alzheimer's disease (AD) calls for multitarget approach for disease management. Herein, a series of novel flurbiprofen-chalcone hybrid Mannich base derivatives were designed and synthesized. The biological screening results indicated that most of the derivatives exhibited potent multi-target effects involved in AD. In particular, compound 6c bearing a pyrrolidine group showed the highest activities against self- and Cu

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Chalcone; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Drug Design; Flurbiprofen; Humans; Mannich Bases; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neuroprotective Agents; Organometallic Compounds; Peptide Fragments; Protein Aggregates; Structure-Activity Relationship

A series of 4'-OH flurbiprofen Mannich base derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound 8n demonstrated the best inhibitory effects on self-induced Aβ

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Blood-Brain Barrier; Cell Line; Cholinesterase Inhibitors; Drug Design; Drug Discovery; Electrophorus; Flurbiprofen; Humans; Mannich Bases; Molecular Docking Simulation; Peptide Fragments; Protein Aggregates; Rats; Swine

A series of chalcone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease based on the multi-target directed ligands design strategy. In vitro assays demonstrated that most of the derivatives exerted potent selective inhibitory potency on AChE with good multifunctional properties. Among them, representative compound 7c exhibited moderate inhibitory potency for EeAChE (IC

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Chalcones; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Drug Design; Eels; Humans; Kinetics; Mannich Bases; Models, Molecular; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neuroprotective Agents; Peptide Fragments; Protein Aggregates; Structure-Activity Relationship

A series of homoisoflavonoid Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease. It demonstrated that most of the derivatives were selective AChE and MAO-B dual inhibitors with good multifunctional properties. Among them, compound 10d displayed the comprehensive advantages, with excellent AChE and MAO-B inhibitory activities (IC

Topics: Acetylcholinesterase; Alzheimer Disease; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Drug Design; Humans; Isoflavones; Mannich Bases; Molecular Docking Simulation; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Structure-Activity Relationship

A series of aurone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compound 7d exhibited outstanding inhibitory activity for RatAChE, EeAChE and HuAChE (IC

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Blood-Brain Barrier; Cholinesterase Inhibitors; Drug Design; Electrophorus; Humans; Mannich Bases; Neuroprotective Agents; PC12 Cells; Rats

A series of pyridoxine-resveratrol hybrids Mannich base derivatives as multifunctional agents have been designed, synthesized and evaluated for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activity. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and metal-chelating properties were also tested. The results showed that most of these compounds could selectively inhibit acetylcholinesterase (AChE) and MAO-B. Among them, compounds 7d and 8b exhibited the highest potency for AChE inhibition with IC

Topics: Acetylcholinesterase; Alzheimer Disease; Animals; Antioxidants; Chelating Agents; Cholinesterase Inhibitors; Electrophorus; Humans; Kinetics; Mannich Bases; Metals; Models, Molecular; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Pyridoxine; Rats; Resveratrol; Stilbenes

Topics: Alzheimer Disease; Alzheimer Vaccines; Amyloid beta-Peptides; Donepezil; Humans; Hypoglycemic Agents; Indans; Mannich Bases; Nootropic Agents; Piperidines; Rosiglitazone; Thiazolidinediones