Please use this identifier to cite or link to this item: http://ir.swu.ac.th/jspui/handle/123456789/12252
Title: Repurposing of Nitroxoline Drug for the Prevention of Neurodegeneration
Authors: Van Hau T.
Ruankham W.
Suwanjang W.
Songtawee N.
Wongchitrat P.
Pingaew R.
Prachayasittikul V.
Prachayasittikul S.
Phopin K.
Keywords: amino acid
catalase
copper zinc superoxide dismutase
hydrogen peroxide
manganese superoxide dismutase
nitroxoline
protein bcl 2
reactive oxygen metabolite
resveratrol
sirtuin 1
transcription factor FKHRL1
FOXO3 protein, human
hydrogen peroxide
nitroquinoline derivative
nitroxoline
protective agent
reactive oxygen metabolite
SIRT1 protein, human
sirtuin 1
transcription factor FKHRL1
antiapoptotic activity
antiinflammatory activity
Article
cell structure
cell survival
cell viability
clinical evaluation
drug mechanism
drug repositioning
flow cytometry
human
human cell
immunofluorescence
microscopy
molecular docking
molecular interaction
MTT assay
nerve cell
nerve degeneration
neurotoxicity
oxidative stress
primary prevention
protein expression
SH-SY5Y cell line
survival rate
upregulation
Western blotting
apoptosis
degenerative disease
dose response
drug effect
metabolism
pathology
tumor cell line
Apoptosis
Cell Line, Tumor
Cell Survival
Dose-Response Relationship, Drug
Drug Repositioning
Forkhead Box Protein O3
Humans
Hydrogen Peroxide
Molecular Docking Simulation
Neurodegenerative Diseases
Neurons
Nitroquinolines
Protective Agents
Reactive Oxygen Species
Sirtuin 1
Issue Date: 2019
Abstract: Oxidative stress has been documented as one of the significant causes of neurodegenerative diseases. Therefore, antioxidant therapy for the prevention of neurodegenerative diseases seems to be an interesting strategy in drug discovery. The quinoline-based compound, namely 5-nitro-8-quinolinol (NQ), has shown excellent antimicrobial, anticancer, and anti-inflammatory activities. However, its neuroprotective effects and precise molecular mechanisms in human neuronal cells have not been elucidated. In this work, the effects of NQ on cell viability and morphology were evaluated by the MTT assay and microscopic observation. Moreover, the underlying mechanisms of this compound, inducing the survival rate of neuronal cells under oxidative stress, were investigated by reactive oxygen species (ROS) assay, flow cytometry, Western blotting, and immunofluorescence techniques. In addition, the molecular interaction of sirtuin1 (SIRT1) with NQ was constructed using the AutoDock 4.2 program. Interestingly, NQ protected SH-SY5Y cells against H2O2-induced neurotoxicity through scavenging ROS, upregulating the levels of SIRT1 and FOXO3a, increasing the levels of antioxidant enzymes (catalase and superoxide dismutase), promoting antiapoptotic BCL-2 protein expression, and reducing apoptosis. Besides, molecular docking also revealed that NQ interacted satisfactorily with the active site of SIRT1 similar to the resveratrol, which is the SIRT1 activator and strong antioxidant. These findings suggest that NQ prevents oxidative-stress-induced neurodegeneration because of its antioxidant capacity as well as antiapoptotic property through SIRT1-FOXO3a signaling pathway. Thus, NQ might be a drug that could be repurposed for prevention of neurodegeneration. © 2019 American Chemical Society.
URI: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074425044&doi=10.1021%2facs.chemrestox.9b00183&partnerID=40&md5=8f6d11c578f99fcc01e862c23be974f9
http://ir.swu.ac.th/jspui/handle/123456789/12252
ISSN: 0893228X
Appears in Collections:SCOPUS 1983-2021

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