Recent Studies of Antioxidant Quinoline Derivatives

Püsküllü, Mustafa Orhan; Tekiner, Betül; Süzen, Síbel

doi:10.2174/138955713804999793

Cited by 33 publications

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“…30 In this conformation, the ligand cannot easily accommodate the preferred tetrahedral geometry of Cu( i ) for redox cycles of Cu( i/ii ) and, thus, is able to inhibit ROS generation. For antioxidant activity, substituents (i.e., both quinoline and phenolic groups, Figure 1) 31–33 known to have antioxidant capability were integrated into ML . Lastly, polar functionalities (e.g., hydroxyl and amino groups) were introduced into the backbone for water solubility.…”

Section: Resultsmentioning

confidence: 99%

Rational Design of a Structural Framework with Potential Use to Develop Chemical Reagents That Target and Modulate Multiple Facets of Alzheimer’s Disease

et al. 2013

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Alzheimer’s disease (AD) is characterized by multiple, intertwined pathological features, including amyloid-β (Aβ) aggregation, metal ion dyshomeostasis, and oxidative stress. We report a novel compound (ML) prototype of a rationally designed molecule obtained by integrating structural elements for Aβ aggregation control, metal chelation, reactive oxygen species (ROS) regulation, and antioxidant activity within a single molecule. Chemical, biochemical, ion mobility mass spectrometric, and NMR studies indicate that the compound ML targets metal-free and metal-bound Aβ (metal–Aβ) species, suppresses Aβ aggregation in vitro, and diminishes toxicity induced by Aβ and metal-treated Aβ in living cells. Comparison of ML to its structural moieties (i.e., 4-(dimethylamino)phenol (DAP) and (8-aminoquinolin-2-yl)methanol (1)) for reactivity with Aβ and metal–Aβ suggests the synergy of incorporating structural components for both metal chelation and Aβ interaction. Moreover, ML is water-soluble and potentially brain permeable, as well as regulates the formation and presence of free radicals. Overall, we demonstrate that a rational structure-based design strategy can generate a small molecule that can target and modulate multiple factors, providing a new tool to uncover and address AD complexity.

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Section: Resultsmentioning

confidence: 99%

Rational Design of a Structural Framework with Potential Use to Develop Chemical Reagents That Target and Modulate Multiple Facets of Alzheimer’s Disease

et al. 2013

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“…CSZ is a quinolone derivative that is considered as an important structural unit in many antioxidant agents (Orhan Püsküllü et al, 2013 ). This study shows that treatment with CSZ significantly decreased the activation of Nox and expression of Nox-4 mRNA in the Aβ-exposed cell (Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

Cilostazol Suppresses Aβ-induced Neurotoxicity in SH-SY5Y Cells through Inhibition of Oxidative Stress and MAPK Signaling Pathway

Oguchi

Ono

Tsuji

et al. 2017

Front. Aging Neurosci.

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Alzheimer's disease (AD) is a slowly progressive form of dementia, characterized by memory impairment and cognitive dysfunction. AD is mainly characterized by the deposition of amyloid β (Aβ) plaques and intracellular neurofibrillary tangles in the brain, along with neuronal degeneration and high levels of oxidative stress. Cilostazol (CSZ) was recently found to suppress the progression of cognitive decline in patients with stable AD receiving acetylcholinesterase inhibitors. This present study aimed to clarify the mechanism by which CSZ protects neurons from degeneration associated with Aβ(1-42). We used Aβ(1-42) to induce neurotoxicity in human neuroblastoma SH-SY5Y cells. Cells were pretreated with CSZ before co-treatment with Aβ. To evaluate the effect of CSZ on oxidative stress, we examined levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate oxidase (Nox) activity, mRNA expression of NOX4, and Cu/Zn-Superoxide Dismutase (SOD), as well as apoptosis biomarkers [MTT, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), caspase-3 and -9 activities and staining of annexin V]. We also assayed the activity of mitogen-activated protein kinases (MAPK): p38 MAPK and extracellular signal-regulated kinase1/2 (ERK1/2), and biomarkers of mitochondrial function (Bcl-2 and Bax), and cyclic adenosine monophosphate response element-binding protein (CREB). Aβ-induced oxidative stress (ROS, NOX4 activity, and expression of NOX mRNA), caspase activation (caspase-3 and -9), and p38 MAPK phosphorylation were suppressed by co-treatment with CSZ, but not by ERK1/2 activation. In addition, pretreatment with CSZ suppressed Aβ-induced apoptosis and increased cell viability via suppression of Bax (a proapoptotic protein), upregulation of Bcl-2 (an antiapoptotic protein) and Cu/Zn-SOD (a superoxide scavenging enzyme), and phosphorylation of CREB.Abbreviations: Aβ, amyloid β; AD, Alzheimer's disease; AMPK, AMP-activated protein kinase; APP, β-amyloid precursor protein; ASK, apoptosis signal-regulating kinase; ATRA, all-trans-retinoic acid; CREB, cyclic adenosine monophosphate response element-binding protein; CSZ, cilostazol; DTT, dithiothreitol; EDTA, ethylenediaminetetraacetic acid; ERK, extracellular signal-regulated kinase; FBS, Fetal bovine serum; HRP, Horseradish Peroxidase; JNK, c-jun N-terminal kinase; MAPK, mitogen-activated protein kinases; MCI, mild cognitive impairment; MEK, MAPK/ERK kinase; MKK, mitogen activated kinase kinase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NADPH, nicotinamide adenine dinucleotide phosphate; NOX, nicotinamide adenine dinucleotide phosphate oxidase; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; PDE, phosphodiesterase; RLU, relative light units; ROS, reactive oxygen species; SOD, Superoxide dismutase; TMB, 3,3 ,5,5 -tetramethylbenzidine. These findings suggested that CSZ could counteract neurotoxicity through multiple mechanisms, one mechanism involving the attenuation of oxidative stress by suppressing NOX activ...

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“…Quinoline and their derivatives play important roles in the synthesis of natural products and as therapeutic agents, and constitute an important class of compounds for new drug development. They have been synthesized by many researchers as model compounds 14 and found to exhibit different pharmacological activities covering anti-cancer, anti-mycobacterial, anti-microbial, anti-convulsant, anti-inflammatory, and cardiovascular activities [15][16][17][18][19] .…”

Section: Introductionmentioning

confidence: 99%

“…Synthetic quinoline derivatives such as 2-chloroquinoline-3-carboxaldehydes 14 , spiro-substituted 4-hydroxypyranoquinolinones 21 , and pyrimido quinoline derivatives 23 have shown significant antioxidant activity. In this study, quinoline derivatives were synthesized in order to investigate whether the quinoline is a substantial heterocyclic bioisoster of the MLT indole moiety.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of antioxidant activity of new quinoline-2-carbaldehyde hydrazone derivatives: bioisosteric melatonin analogues

Püsküllü

Shirinzadeh

Nenni

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Overproduction of reactive oxygen species results in oxidative stress that can cause fatal damage to vital cell structures. It is known that the use of antioxidants could be beneficial in the prevention or delay of numerous diseases associated with oxidative stress. Melatonin (MLT) is known as a powerful free-radical scavenger and antioxidant. It was found that indole ring of MLT can be employed by bioisosteric replacement by other aromatic rings. Quinoline derivatives constitute an important class of compounds for new drug development. Owing to quinoline and hydrazones appealing physiological properties and are mostly found in numerous biologically active compounds a series of quinoline-2-carbaldehyde hydrazone derivatives were synthesized as bioisosteric analogues of MLT, characterized and in vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Cytotoxicity potential of all compounds was investigated both by lactate dehydrogenase leakage assay and by MTT assay.

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Recent Studies of Antioxidant Quinoline Derivatives

Cited by 33 publications

References 0 publications

Rational Design of a Structural Framework with Potential Use to Develop Chemical Reagents That Target and Modulate Multiple Facets of Alzheimer’s Disease

Rational Design of a Structural Framework with Potential Use to Develop Chemical Reagents That Target and Modulate Multiple Facets of Alzheimer’s Disease

Cilostazol Suppresses Aβ-induced Neurotoxicity in SH-SY5Y Cells through Inhibition of Oxidative Stress and MAPK Signaling Pathway

Synthesis and evaluation of antioxidant activity of new quinoline-2-carbaldehyde hydrazone derivatives: bioisosteric melatonin analogues

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