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Design, synthesis, and evaluation of salicyladimine derivatives as multitarget-directed ligands against Alzheimer's disease
- Source :
- Bioorganicmedicinal chemistry. 25(21)
- Publication Year :
- 2017
-
Abstract
- A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid-β (Aβ) aggregation and human monoamine oxidase B (hMAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5, exhibited excellent potency for inhibition of self-induced Aβ1-42 aggregation (91.3±2.1%, 25μM), inhibition of hMAO-B (IC50, 1.73±0.39μM), antioxidant effects (43.4±2.6μM of IC50 by DPPH method, 0.67±0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H2O2-induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs.
- Subjects :
- 0301 basic medicine
Lipopolysaccharides
Antioxidant
Monoamine Oxidase Inhibitors
DPPH
Cell Survival
medicine.medical_treatment
Clinical Biochemistry
Pharmaceutical Science
Ligands
01 natural sciences
Biochemistry
Neuroprotection
PC12 Cells
03 medical and health sciences
chemistry.chemical_compound
Mice
Protein Aggregates
Structure-Activity Relationship
Alzheimer Disease
Drug Discovery
medicine
Animals
Humans
Molecular Biology
IC50
Monoamine Oxidase
ABTS
Amyloid beta-Peptides
Dose-Response Relationship, Drug
Molecular Structure
010405 organic chemistry
Organic Chemistry
Biological activity
Hydrogen Peroxide
Peptide Fragments
Salicylates
0104 chemical sciences
Rats
Molecular Docking Simulation
030104 developmental biology
chemistry
Drug Design
Molecular Medicine
Trolox
Monoamine oxidase B
Imines
Microglia
Subjects
Details
- ISSN :
- 14643391
- Volume :
- 25
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry
- Accession number :
- edsair.doi.dedup.....9e1df1e5d444be44e8fdbf67dcaf38d4