Lipid Peroxidation and Antioxidant Protection

Valgimigli, Luca

doi:10.3390/biom13091291

Cited by 47 publications

(27 citation statements)

References 152 publications

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“…In LP, a mixture of many different radicals is formed, the quenching mechanism of which may differ from the hydroxyl radical. Despite this, the BDE can be considered a rough but adequate characterization of AOA [ 68 ].…”

Section: Resultsmentioning

confidence: 99%

Combining Experimental and Computational Methods to Produce Conjugates of Anticholinesterase and Antioxidant Pharmacophores with Linker Chemistries Affecting Biological Activities Related to Treatment of Alzheimer’s Disease

Makhaeva,

Kovaleva,

Rudakova

et al. 2024

Molecules

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Effective therapeutics for Alzheimer’s disease (AD) are in great demand worldwide. In our previous work, we responded to this need by synthesizing novel drug candidates consisting of 4-amino-2,3-polymethylenequinolines conjugated with butylated hydroxytoluene via fixed-length alkylimine or alkylamine linkers (spacers) and studying their bioactivities pertaining to AD treatment. Here, we report significant extensions of these studies, including the use of variable-length spacers and more detailed biological characterizations. Conjugates were potent inhibitors of acetylcholinesterase (AChE, the most active was 17d IC50 15.1 ± 0.2 nM) and butyrylcholinesterase (BChE, the most active was 18d: IC50 5.96 ± 0.58 nM), with weak inhibition of off-target carboxylesterase. Conjugates with alkylamine spacers were more effective cholinesterase inhibitors than alkylimine analogs. Optimal inhibition for AChE was exhibited by cyclohexaquinoline and for BChE by cycloheptaquinoline. Increasing spacer length elevated the potency against both cholinesterases. Structure–activity relationships agreed with docking results. Mixed-type reversible AChE inhibition, dual docking to catalytic and peripheral anionic sites, and propidium iodide displacement suggested the potential of hybrids to block AChE-induced β-amyloid (Aβ) aggregation. Hybrids also exhibited the inhibition of Aβ self-aggregation in the thioflavin test; those with a hexaquinoline ring and C8 spacer were the most active. Conjugates demonstrated high antioxidant activity in ABTS and FRAP assays as well as the inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Quantum-chemical calculations explained antioxidant results. Computed ADMET profiles indicated favorable blood–brain barrier permeability, suggesting the CNS activity potential. Thus, the conjugates could be considered promising multifunctional agents for the potential treatment of AD.

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Section: Resultsmentioning

confidence: 99%

Combining Experimental and Computational Methods to Produce Conjugates of Anticholinesterase and Antioxidant Pharmacophores with Linker Chemistries Affecting Biological Activities Related to Treatment of Alzheimer’s Disease

Makhaeva,

Kovaleva,

Rudakova

et al. 2024

Molecules

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“…The lipid peroxidation mechanism involves the oxidation of lipids or fatty acids which causes cell damage. 36,37 Excessive accumulation of lipid peroxides causes ferroptosis. 38,39 Excessive ROS generation causes oxidative stress, promotes lipid peroxidation, and leads to the rapid overproduction of MDA (lipid peroxidation product).…”

Section: Discussionmentioning

confidence: 99%

Cynarin alleviates acetaminophen-induced acute liver injury through the activation of Keap1/Nrf2-mediated lipid peroxidation defense via the AMPK/SIRT3 signaling pathway

Zhao,

Zhang,

Chen

et al. 2024

Food Funct.

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“…Vitamin C (1 μM) also prevents lipid peroxidation by clearing ROS and maintaining the levels of antioxidants [ 172 , 173 ]. Thus, the development of ferroptosis is inhibited [ 172 ], allowing us to speculate that the damage ferroptosis causes to cardiomyocytes after MI may be inhibited by vitamin C.…”

Section: The Role Of Vitamin C In Cardiovascular Pathologiesmentioning

confidence: 99%

Vitamin C as Scavenger of Reactive Oxygen Species during Healing after Myocardial Infarction

Zheng,

Xu,

Liehn

et al. 2024

IJMS

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Currently, coronary artery bypass and reperfusion therapies are considered the gold standard in long-term treatments to restore heart function after acute myocardial infarction. As a drawback of these restoring strategies, reperfusion after an ischemic insult and sudden oxygen exposure lead to the exacerbated synthesis of additional reactive oxidative species and the persistence of increased oxidation levels. Attempts based on antioxidant treatment have failed to achieve an effective therapy for cardiovascular disease patients. The controversial use of vitamin C as an antioxidant in clinical practice is comprehensively systematized and discussed in this review. The dose-dependent adsorption and release kinetics mechanism of vitamin C is complex; however, this review may provide a holistic perspective on its potential as a preventive supplement and/or for combined precise and targeted therapeutics in cardiovascular management therapy.

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Lipid Peroxidation and Antioxidant Protection

Cited by 47 publications

References 152 publications

Combining Experimental and Computational Methods to Produce Conjugates of Anticholinesterase and Antioxidant Pharmacophores with Linker Chemistries Affecting Biological Activities Related to Treatment of Alzheimer’s Disease

Combining Experimental and Computational Methods to Produce Conjugates of Anticholinesterase and Antioxidant Pharmacophores with Linker Chemistries Affecting Biological Activities Related to Treatment of Alzheimer’s Disease

Cynarin alleviates acetaminophen-induced acute liver injury through the activation of Keap1/Nrf2-mediated lipid peroxidation defense via the AMPK/SIRT3 signaling pathway

Vitamin C as Scavenger of Reactive Oxygen Species during Healing after Myocardial Infarction

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