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Synthesis and pharmacological evaluation of novel chromone derivatives as balanced multifunctional agents against Alzheimer's disease
- Source :
- Bioorganicmedicinal chemistry. 25(14)
- Publication Year :
- 2017
-
Abstract
- In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of chromone derivatives were designed, synthesized and evaluated. In vitro assay indicated that most of the target compounds have both MAOs inhibition activities, antioxidant activity and biometal chelating ability. Especially, compound s19 exhibits good inhibitory potency for inhibition of MAOs (IC50 value of 5.12μM for hMAO-A and 0.816μM for hMAO-B), moderate inhibition of Aβ aggregation (75.1% at 20μM), metal chelation, control of ROS generation and antioxidant activity (ORAC=3.62). In addition, s19 could reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). Taken together, these results suggested that s19 might be a promising multitargeted compound for AD treatment.
- Subjects :
- Antioxidant
Monoamine Oxidase Inhibitors
medicine.medical_treatment
Clinical Biochemistry
Pharmaceutical Science
Apoptosis
Pharmacology
010402 general chemistry
medicine.disease_cause
01 natural sciences
Biochemistry
PC12 Cells
Antioxidants
chemistry.chemical_compound
Inhibitory Concentration 50
Structure-Activity Relationship
Alzheimer Disease
Drug Discovery
medicine
Animals
Humans
Chelation
Molecular Biology
IC50
Monoamine Oxidase
Amyloid beta-Peptides
Binding Sites
010405 organic chemistry
Chemistry
Organic Chemistry
Hydrogen Peroxide
In vitro
0104 chemical sciences
Protein Structure, Tertiary
Rats
Metal chelation
Molecular Docking Simulation
Inhibitory potency
Oxidative Stress
Neuroprotective Agents
Blood-Brain Barrier
Chromones
Chromone
Molecular Medicine
Reactive Oxygen Species
Oxidative stress
Copper
Subjects
Details
- ISSN :
- 14643391
- Volume :
- 25
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry
- Accession number :
- edsair.doi.dedup.....9317a05b5381d94f69705a1fa24b4a36