Hydroxypyridinone-Diamine Hybrids as Potential Neuroprotective Agents in the PC12 Cell-Line Model of Alzheimer’s Disease

Lohou, Elodie; Sasaki, Naoki; Boullier, Agnès; Duplantier, Marine; Sonnet, Pascal

doi:10.3390/ph12040162

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…Biometal‐catalyzed hydroxyl radicals are effective mediators of cellular damage, which can lead to aggravation of oxidative stress and the rapid formation of β ‐amyloid [36] . Considering these factors, metal chelators were of importance to the treatment of AD.…”

Section: Resultsmentioning

confidence: 99%

“…Biometal-catalyzed hydroxyl radicals are effective mediators of cellular damage, which can lead to aggravation of oxidative stress and the rapid formation of β-amyloid. [36] Considering these factors, metal chelators were of importance to the treatment of AD. Thus, we used UV-Vis spectrometry to study the chelation abilities of compound 4 e towards Fe 2 + , Cu 2 + and Zn 2 + .…”

Section: Metal-chelating Studymentioning

confidence: 99%

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Design, Synthesis, Biological Evaluation and Molecular Dynamics Simulations Study of Genistein‐O‐1,3,5‐Triazine Derivatives as Multifunctional Anti‐Alzheimer Agents

Zou¹,

Qian²,

Liu³

et al. 2022

ChemistrySelect

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Twenty-four genistein-O-1,3,5-triazine derivatives were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. These compounds were confirmed by IR, NMR and HRMS and single-crystal X-ray diffraction studies. Most target compounds showed good inhibition and selectivity to acetylcholinesterase. Among these compounds, compound 4 e (7-((4-chloro-6-(diisobutylamino)-1,3,5-triazin-2-yl)oxy)-5hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one) exhibited the strongest inhibition to acetylcholinesterase with IC 50 of 0.034 μM, which was comparable with that of donepezil (IC 50 = 0.037 μM). The enzyme kinetics studies showed that this compound was a kind of mixed type inhibitor. Molecular docking and molecular dynamics simulations study of this compound indicated that it could interact with the crucial amino acids present at the catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase and bind to acetylcholinesterase stably. Furthermore, this compound also showed terrific metal chelating abilities. ADMET characteristics implied that these compounds could possess the properties to become drug candidates. Thus, this compound may become a latent multifunctional anti-Alzheimer agent.

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Section: Resultsmentioning

confidence: 99%

Section: Metal-chelating Studymentioning

confidence: 99%

Design, Synthesis, Biological Evaluation and Molecular Dynamics Simulations Study of Genistein‐O‐1,3,5‐Triazine Derivatives as Multifunctional Anti‐Alzheimer Agents

Zou¹,

Qian²,

Liu³

et al. 2022

ChemistrySelect

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show abstract

“…MGO is a reactive carbonyl ketone that can irreversibly react with protein amino acid residues to produce AGEs (Lohou et al, 2019). The aggregation of AGEs is a distinct feature of diabetic patients or model animals (Jack & Wright, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…MGO is a reactive carbonyl ketone that can irreversibly react with protein amino acid residues to produce AGEs (Lohou et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Lutein attenuated methylglyoxal‐induced oxidative damage and apoptosis in PC12 cells via the PI3K /Akt signaling pathway

Chen

Zhang

Liu

et al. 2022

Journal of Food Biochemistry

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Methylglyoxal (MGO), a cytotoxic byproduct of glycolysis, causes neuro oxidative damage and apoptosis, and plays key roles in diabetic encephalopathy (DE). The goal of this research was to evaluate the roles of lutein attenuated MGO‐induced damage in PC12 cells as well as the underlying mechanisms. The findings of this study showed that lutein has a significant impact on reducing the generation of reactive oxygen species (ROS) and oxidative stress in MGO‐induced PC12 cells, which may be attributed to the increased antioxidant enzymes activity and the decreased MDA levels. Moreover, treatment with lutein also alleviated cell apoptosis and mitochondrial damage. Real‐time PCR and western blot analysis showed that lutein enhanced the Bcl‐2:Bax ratio, inhibited the expression of caspase‐3 and caspase‐9, and increased the protein level of phosphorylated Akt. The network pharmacology and molecular docking prediction results suggested that the phosphoinositide 3‐kinase/protein kinase B (PI3K/Akt) signaling pathway was a potential mechanism of lutein in DE treatment. Furthermore, LY294002, a specific PI3K inhibitor, partially abolished the protective effect of lutein. These results presented that lutein attenuated oxidative damage and apoptosis triggered by MGO in PC12 cells via the PI3K/Akt signaling pathway. Practical applications Lutein is a common carotenoid dispersed in fruits and vegetables. This article confirmed a protective effect of lutein on oxidative damage and apoptosis in PC12 cells after MGO damage. These results indicated that lutein could potentially be developed as a nutraceutical or functional food in the prevention of diabetic‐related neurodegenerative diseases.

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Recent advances in therapeutical applications of the versatile hydroxypyridinone chelators

Sharma

Baral

Kanungo

2022

J Incl Phenom Macrocycl Chem

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Hydroxypyridinone-Diamine Hybrids as Potential Neuroprotective Agents in the PC12 Cell-Line Model of Alzheimer’s Disease

Cited by 5 publications

References 29 publications

Design, Synthesis, Biological Evaluation and Molecular Dynamics Simulations Study of Genistein‐O‐1,3,5‐Triazine Derivatives as Multifunctional Anti‐Alzheimer Agents

Design, Synthesis, Biological Evaluation and Molecular Dynamics Simulations Study of Genistein‐O‐1,3,5‐Triazine Derivatives as Multifunctional Anti‐Alzheimer Agents

Lutein attenuated methylglyoxal‐induced oxidative damage and apoptosis in PC12 cells via the PI3K /Akt signaling pathway

Recent advances in therapeutical applications of the versatile hydroxypyridinone chelators

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