Publication:
Novel multifunctional ascorbic triazole derivatives for amyloidogenic pathway inhibition, anti-inflammation, and neuroprotection

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Issued Date

2021

Resource Type

Article

Language

eng

File Type

application/pdf

ISSN

14203049

DOI

10.3390/molecules26061562

Other identifier(s)

2-s2.0-85103862243

Rights Holder(s)

Scopus

Bibliographic Citation

Molecules. Vol 26, No.6 (2021)

Suggested Citation

Jiaranaikulwanitch J., Pandith H., Tadtong S., Thammarat P., Jiranusornkul S., Chauthong N., Nilkosol S., Vajragupta O. Novel multifunctional ascorbic triazole derivatives for amyloidogenic pathway inhibition, anti-inflammation, and neuroprotection. Molecules. Vol 26, No.6 (2021). doi:10.3390/molecules26061562 Retrieved from: https://hdl.handle.net/20.500.14740/7855

Title

Novel multifunctional ascorbic triazole derivatives for amyloidogenic pathway inhibition, anti-inflammation, and neuroprotection

Author(s)

Jiaranaikulwanitch J.
 Pandith H.
 Tadtong S.
 Thammarat P.
 Jiranusornkul S.
 Chauthong N.
 Nilkosol S.
 Vajragupta O.

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disorder. The number of patients with AD is projected to reach 152 million by 2050. Donepezil, rivastigmine, galantamine, and memantine are the only four drugs currently approved by the United States Food and Drug Administration for AD treatment. However, these drugs can only alleviate AD symptoms. Thus, this research focuses on the discovery of novel lead compounds that possess multitarget regulation of AD etiopathology relating to amyloid cascade. The ascorbic acid structure has been designated as a core functional domain due to several characteristics, including antioxidant activities, amyloid aggregation inhibition, and the ability to be transported to the brain and neurons. Multifunctional ascorbic derivatives were synthesized by copper (I)-catalyzed azide–alkyne cycloaddition reaction (click chemistry). The in vitro and cell-based assays showed that compounds 2c and 5c exhibited prominent multifunctional activities as beta-secretase 1 inhibitors, amyloid aggregation inhibitors, and antioxidant, neuroprotectant, and anti-inflammatory agents. Significant changes in activities promoting neuroprotection and anti-inflammation were observed at a considerably low concentration at a nanomolar level. Moreover, an in silico study showed that compounds 2c and 5c were capable of being permeated across the blood–brain barrier by sodium-dependent vitamin C transporter-2. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Subject(s)

Amyloid beta protein
 Amyloid protein
 Antiinflammatory agent
 Ascorbic acid
 Cyclooxygenase 2
 Inducible nitric oxide synthase
 Neuroprotective agent
 Nos2 protein, mouse
 Ptgs2 protein, mouse
 SLC23A2 protein, human
 Sodium ascorbic acid cotransporter
 Triazole derivative
 Alzheimer disease
 Animal
 Binding site
 Blood brain barrier
 Cell culture
 Chemical structure
 Chemistry
 Computer simulation
 Drug effect
 Gene expression
 Genetics
 Human
 Metabolism
 Molecular docking
 Mouse
 RAW 264.7 cell line
 Structure activity relation
 Synthesis
 Alzheimer Disease
 Amyloid beta-Peptides
 Amyloidogenic Proteins
 Animals
 Anti-Inflammatory Agents
 Ascorbic Acid
 Binding Sites
 Blood-Brain Barrier
 Cells, Cultured
 Computer Simulation
 Cyclooxygenase 2
 Gene Expression
 Humans
 Mice
 Molecular Docking Simulation
 Molecular Structure
 Neuroprotective Agents
 Nitric Oxide Synthase Type II
 RAW 264.7 Cells
 Sodium-Coupled Vitamin C Transporters
 Structure-Activity Relationship
 Triazoles

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URI

https://hdl.handle.net/20.500.14740/7855

Collections

Scopus: Year 1983-2021

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