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Your search keyword '"Zheng, Yunxiaozhu"' showing total 2 results
Start Over Author "Zheng, Yunxiaozhu" Topic monoamine oxidase
2 results on '"Zheng, Yunxiaozhu"'

1. Multifunctional 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives with acetylcholinesterase, monoamine oxidases and β-amyloid aggregation inhibitory activities as potential agents against Alzheimer's disease.

Author

Xu R, Xiao G, Li Y, Liu H, Song Q, Zhang X, Yang Z, Zheng Y, Tan Z, and Deng Y

Subjects
Acetylcholinesterase chemistry, Alzheimer Disease drug therapy, Alzheimer Disease pathology, Amyloid beta-Peptides chemistry, Antioxidants chemistry, Antioxidants metabolism, Benzylamines metabolism, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Cholinesterase Inhibitors metabolism, Cholinesterase Inhibitors therapeutic use, Drug Design, Humans, Kinetics, Monoamine Oxidase chemistry, Monoamine Oxidase genetics, Monoamine Oxidase Inhibitors metabolism, Monoamine Oxidase Inhibitors therapeutic use, Permeability drug effects, Protein Aggregates drug effects, Recombinant Proteins chemistry, Recombinant Proteins metabolism, Structure-Activity Relationship, Thiazoles chemistry, Acetylcholinesterase metabolism, Amyloid beta-Peptides metabolism, Benzylamines chemistry, Cholinesterase Inhibitors chemistry, Monoamine Oxidase metabolism, Monoamine Oxidase Inhibitors chemistry
Abstract

A series of 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro assays indicated that most of these derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compounds 11b and 11d displayed comprehensive advantages, with good AChE (IC 50  = 0.29 ± 0.01 μM and 0.46 ± 0.02 μM, respectively), MAO-A (IC 50  = 8.2 ± 0.08 μM and 7.9 ± 0.07 μM, respectively) and MAO-B (IC 50  = 20.1 ± 0.16 μM and 43.8 ± 2.0% at 10 μM, respectively) inhibitory activities, moderate self-induced Aβ 1-42 aggregation inhibitory potency (35.4 ± 0.42% and 48.0 ± 1.53% at 25 μM, respectively) and potential antioxidant activity. In addition, the two representative compounds displayed high BBB permeability in vitro. Taken together, these multifunctional properties make 11b and 11d as a promising candidate for the development of efficient drugs against AD., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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2. Pyridoxine-resveratrol hybrids Mannich base derivatives as novel dual inhibitors of AChE and MAO-B with antioxidant and metal-chelating properties for the treatment of Alzheimer's disease.

Author

Yang X, Qiang X, Li Y, Luo L, Xu R, Zheng Y, Cao Z, Tan Z, and Deng Y

Subjects
Acetylcholinesterase metabolism, Alzheimer Disease drug therapy, Alzheimer Disease enzymology, Animals, Antioxidants chemistry, Chelating Agents chemistry, Cholinesterase Inhibitors chemistry, Electrophorus, Humans, Kinetics, Mannich Bases chemistry, Mannich Bases pharmacology, Metals metabolism, Models, Molecular, Monoamine Oxidase Inhibitors chemistry, Pyridoxine analogs & derivatives, Rats, Resveratrol, Stilbenes chemistry, Antioxidants pharmacology, Chelating Agents pharmacology, Cholinesterase Inhibitors pharmacology, Monoamine Oxidase metabolism, Monoamine Oxidase Inhibitors pharmacology, Pyridoxine pharmacology, Stilbenes pharmacology
Abstract

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 50 values of 2.11μM and 1.56μM, respectively, and compound 7e exhibited the highest MAO-B inhibition with an IC 50 value of 2.68μM. The inhibition kinetic analysis revealed that compound 7d showed a mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. Molecular modeling study was also performed to investigate the binding mode of these hybrids with MAO-B. In addition, all target compounds displayed good antioxidant and metal-chelating properties. Taken together, these preliminary findings can be a new starting point for further development of multifunctional agents for Alzheimer's disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Published
2017
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