Publication: Neuritogenic activity of bi-functional bis-tryptoline triazole
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0
Issued Date
2017
Resource Type
File Type
application/pdf
ISSN
9680896
Other identifier(s)
2-s2.0-85009471336
Rights Holder(s)
Scopus
Bibliographic Citation
Bioorganic and Medicinal Chemistry. Vol 25, No.3 (2017), p.1195-1201
Suggested Citation
Jiaranaikulwanitch J., Tadtong S., Govitrapong P., Fokin V.V., Vajragupta O. Neuritogenic activity of bi-functional bis-tryptoline triazole. Bioorganic and Medicinal Chemistry. Vol 25, No.3 (2017), p.1195-1201. doi:10.1016/j.bmc.2016.12.027 Retrieved from: https://hdl.handle.net/20.500.14740/4813
Abstract
Alzheimer's disease (AD) is a common neurodegenerative disorder, one of the hallmarks of which is the deposition of aggregated β-amyloid peptides (Aβ40,42) as plaques in the brain. Oligomers of these peptides have been reported to be toxic and to inhibit neurite outgrowth, as evidenced by neurite dystrophy and significant loss of synaptic connectivity of neurons in the AD brain resulting in cognitive decline. These peptides also react with biological metal in the brain to generate free radicals, thereby aggravating neuronal cell injury and death. Herein, multifunctional triazole-based compounds acting on multiple targets, namely β-secretase (BACE1), β-amyloid peptides (Aβ) as well as those possessing metal chelation and antioxidant properties, were developed and evaluated for neuritogenic activity in P19-derived neurons. At the non-cytotoxic concentration (1 nM), all multifunctional compounds significantly enhanced neurite outgrowth. New bis-tryptoline triazole (BTT) increased the neurite length and neurite number, by 93.25% and 136.09% over the control, respectively. This finding demonstrates the ability of multifunctional compounds targeting Aβ to enhance neurite outgrowth in addition to their neuroprotective action. © 2016 Elsevier Ltd
Subject(s)
Amyloid beta protein
Beta secretase
Bis tryptoline triazole derivative
Geldanamycin
Quercetin
Triazole derivative
Unclassified drug
Aspartic proteinase
BACE1 protein, human
Carboline derivative
Enzyme inhibitor
Neuroprotective agent
Secretase
Triazole derivative
Tryptoline
Antioxidant activity
Article
Chelation
Concentration response
Controlled study
Cytotoxicity
Drug activity
Drug screening
Drug structure
Drug targeting
Nerve cell
Neurite outgrowth
Neuritogenic activity
Neuroprotection
Animal
Antagonists and inhibitors
Cell line
Cell survival
Chemical structure
Chemistry
Dose response
Drug effects
Human
Metabolism
Mouse
Neurite
Structure activity relation
Synthesis
Amyloid Precursor Protein Secretases
Animals
Aspartic Acid Endopeptidases
Carbolines
Cell Line
Cell Survival
Dose-Response Relationship, Drug
Enzyme Inhibitors
Humans
Mice
Molecular Structure
Neurites
Neuroprotective Agents
Structure-Activity Relationship
Triazoles
Beta secretase
Bis tryptoline triazole derivative
Geldanamycin
Quercetin
Triazole derivative
Unclassified drug
Aspartic proteinase
BACE1 protein, human
Carboline derivative
Enzyme inhibitor
Neuroprotective agent
Secretase
Triazole derivative
Tryptoline
Antioxidant activity
Article
Chelation
Concentration response
Controlled study
Cytotoxicity
Drug activity
Drug screening
Drug structure
Drug targeting
Nerve cell
Neurite outgrowth
Neuritogenic activity
Neuroprotection
Animal
Antagonists and inhibitors
Cell line
Cell survival
Chemical structure
Chemistry
Dose response
Drug effects
Human
Metabolism
Mouse
Neurite
Structure activity relation
Synthesis
Amyloid Precursor Protein Secretases
Animals
Aspartic Acid Endopeptidases
Carbolines
Cell Line
Cell Survival
Dose-Response Relationship, Drug
Enzyme Inhibitors
Humans
Mice
Molecular Structure
Neurites
Neuroprotective Agents
Structure-Activity Relationship
Triazoles