Publication:
Repurposing of Nitroxoline Drug for the Prevention of Neurodegeneration

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Issued Date

2019

Resource Type

Article

File Type

application/pdf

ISSN

0893228X

DOI

10.1021/acs.chemrestox.9b00183

Other identifier(s)

2-s2.0-85074425044

Rights Holder(s)

Scopus

Bibliographic Citation

Chemical Research in Toxicology. Vol 32, No.11 (2019), p.2182-2191

Suggested Citation

Van Hau T., Ruankham W., Suwanjang W., Songtawee N., Wongchitrat P., Pingaew R., Prachayasittikul V., Prachayasittikul S., Phopin K. Repurposing of Nitroxoline Drug for the Prevention of Neurodegeneration. Chemical Research in Toxicology. Vol 32, No.11 (2019), p.2182-2191. doi:10.1021/acs.chemrestox.9b00183 Retrieved from: https://hdl.handle.net/20.500.14740/5083

Title

Repurposing of Nitroxoline Drug for the Prevention of Neurodegeneration

Author(s)

Van Hau T.
 Ruankham W.
 Suwanjang W.
 Songtawee N.
 Wongchitrat P.
 Pingaew R.
 Prachayasittikul V.
 Prachayasittikul S.
 Phopin K.

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.

Subject(s)

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

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URI

https://hdl.handle.net/20.500.14740/5083

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Scopus: Year 1983-2021

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