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Antioxidants
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Catalytic Antioxidants
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Catalytic Antioxidants

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Natural and Synthetic Antioxidants".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 26888

Special Issue Editor

Prof. Dr. Stefano Menichetti

E-Mail Website
Guest Editor
Department of Chemistry “Ugo Schiff”, University of Florence, Via Della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy
Interests: design, synthesis and structure-activity relationship of bio-inspired multi-defence antioxidants; chalcogen containing phenolic antioxidants; macromolecular and nano-supported antioxidants
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The formation of free radicals and other reactive oxygen species (ROS) in living tissues is an unavoidable consequence of aerobic metabolism. Today, it is well recognized that oxygen-centered free radicals are often useful intermediates involved in crucial biochemical transformations. However, it has been solidly demonstrated that an anomalous high concentration of ROS is directly related to tissue oxidative stress and ageing, as well as being an origin and consequence of many of the more dangerous diseases. Evolution has provided endogenous and exogenous defences for keeping the ROS concentration under control. The intake of small molecules that are able to break the chain of radical reactions leading to oxidative damage is a simple and efficient exogenous solution. A diet rich in antioxidants can play a crucial role in health, particularly in countries where the factors responsible for dangerously increasing the concentration of ROS (stress, smoke, over alimentation, alcohol and drug abuse, and pollution) are frequent lifestyle components. On the other hand, the expression of specific enzymes that are able to quench or avoid the formation of ROS and dangerous free radicals (i.e., superoxide dismutase, catalase, glutathione peroxidase) is an endogenous answer to this problem. In the last year, remarkable effort has been made to study antioxidants that can mimic these enzymes, ensuring protection when used in a catalytic amount. This enzyme mimicry can be achieved by either favouring a disproportionation process (for example, in superoxide dismutase or catalase like systems) or exploiting a sacrificial reductant consumed during the process (for example, in glutathione peroxidase mimic compounds).

The aim of this Special Issue of Antioxidants is to present a collection of the latest research on catalytic antioxidants. In particular, we are focused on molecular actions at the biological level of natural derivatives in relation to the design, synthesis, and effectiveness of synthetic derivatives.

We look forward to your contribution.

Prof. Stefano Menichetti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • catalytic antioxidants
  • enzyme-like activity
  • bioinspired design

Published Papers (6 papers)

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Research

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10 pages, 1363 KiB  
Article
A Synthetic SOD/Catalase Mimic Compound for the Treatment of ALS
by Matan Soll, Hagit Goldshtein, Ron Rotkopf, Niva Russek-Blum and Zeev Gross
Antioxidants 2021, 10(6), 827; https://doi.org/10.3390/antiox10060827 - 22 May 2021
Cited by 8 | Viewed by 3247
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. To date, the etiology of the disease is still unclear, with evidence of reactive oxygen species, mitochondrial dysfunction, iron homeostasis perturbation, protein misfolding and protein aggregation as key players in the [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. To date, the etiology of the disease is still unclear, with evidence of reactive oxygen species, mitochondrial dysfunction, iron homeostasis perturbation, protein misfolding and protein aggregation as key players in the pathology of the disease. Twenty percent of familial ALS and two percent of sporadic ALS instances are due to a mutation in Cu/Zn superoxide dismutase (SOD1). Sporadic and familial ALS affects the same neurons with similar pathology; therefore, the underlying hypothesis is that therapies effective in mutant SOD1 models could be translated to sporadic ALS. Corrole metal complexes have lately been identified as strong and potent catalytic antioxidants with beneficial effects in oxidative stress-related diseases such as Parkinson’s disease, Alzheimer’s disease, atherosclerosis, diabetes and its complications. One of the most promising candidates is the iron complex of an amphiphilic corrole, 1-Fe. In this study we used the SOD1 G93R mutant zebrafish ALS model to assess whether 1-Fe, as a potent catalytic antioxidant, displays any therapeutic merits in vivo. Our results show that 1-Fe caused a substantial increase in mutant zebrafish locomotor activity (up to 30%), bringing the locomotive abilities of the mutant treated group close to that of the wild type untreated group (50% more than the mutated untreated group). Furthermore, 1-Fe did not affect WT larvae locomotor activity, suggesting that 1-Fe enhances locomotor ability by targeting mechanisms underlying SOD1 ALS specifically. These results may pave the way for future development of 1-Fe as a viable treatment for ALS. Full article
(This article belongs to the Special Issue Catalytic Antioxidants)
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20 pages, 17161 KiB  
Article
Hybrid Heme Peroxidases from Rice Blast Fungus Magnaporthe oryzae Involved in Defence against Oxidative Stress
by Marcel Zámocký, Anna Kamlárová, Daniel Maresch, Katarína Chovanová, Jana Harichová and Paul G. Furtmüller
Antioxidants 2020, 9(8), 655; https://doi.org/10.3390/antiox9080655 - 23 Jul 2020
Cited by 9 | Viewed by 5263
Abstract
Hybrid B heme peroxidases are recently discovered unique oxidoreductases present solely in the fungal kingdom. We have investigated two typical representatives from Magnaporthe oryzae—one of the most dangerous phytopathogens known as a causal agent of the rice blast disease. First, we focused [...] Read more.
Hybrid B heme peroxidases are recently discovered unique oxidoreductases present solely in the fungal kingdom. We have investigated two typical representatives from Magnaporthe oryzae—one of the most dangerous phytopathogens known as a causal agent of the rice blast disease. First, we focused on native expression of two detected hyBpox paralogs by the means of reverse-transcription quantitative real-time PCR. Our results indicate a 7-fold induction of the MohyBpox1 transcript in a medium with H2O2 and a 3-fold induction in a medium with peroxyacetic acid. For the MohyBpox2 paralog the induction patterns were up to 12-fold and 6.7-fold, respectively. We have successfully expressed the shorter gene, MohyBpox1, heterologously in Pichia pastoris for detailed characterization. Observed biochemical and biophysical properties of the highly purified protein reveal that a typical HyBPOX is significantly different from previously investigated APx-CcP hybrids. This newly discovered secretory peroxidase reveals a Soret maximum at 407 nm, Q bands at 532 and 568 nm, CT band at 625 nm and a purity number of 1.48. Electron paramagnetic resonance (EPR) analysis suggests a mixture of high and low spin species in the ferric state dependent on calcium contents. Steady-state kinetic data reveal the highest peroxidase activity with ABTS, 5-aminosalycilate and efficient oxidation of tyrosine. MoHyBPOX1 as a fusion protein consists of two domains. The longer conserved N-terminal peroxidase domain is connected with a shorter C-terminal domain containing a carbohydrate binding motif of type CBM21. We demonstrate the capacity of MoHyBPOX1 to bind soluble starch efficiently. Potential involvement of hybrid peroxidases in the pathogenicity of M. oryzae is discussed. Full article
(This article belongs to the Special Issue Catalytic Antioxidants)
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16 pages, 4955 KiB  
Article
Fe Porphyrin-Based SOD Mimic and Redox-Active Compound, (OH)FeTnHex-2-PyP4+, in a Rodent Ischemic Stroke (MCAO) Model: Efficacy and Pharmacokinetics as Compared to Its Mn Analogue, (H2O)MnTnHex-2-PyP5+
by Litao Li, Artak Tovmasyan, Huaxin Sheng, Bin Xu, Romulo S. Sampaio, Julio S. Reboucas, David S. Warner, Ines Batinic-Haberle and Ivan Spasojevic
Antioxidants 2020, 9(6), 467; https://doi.org/10.3390/antiox9060467 - 01 Jun 2020
Cited by 8 | Viewed by 2872
Abstract
Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, (H2O)MnTnHex-2-PyP5+ (MnHex) carrying long hexyl chains, is a lipophilic mimic of superoxide dismutase (SOD) and a redox-active drug candidate. MnHex crosses the blood–brain barrier, and improved neurologic outcome and decreased infarct size and inflammation in [...] Read more.
Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, (H2O)MnTnHex-2-PyP5+ (MnHex) carrying long hexyl chains, is a lipophilic mimic of superoxide dismutase (SOD) and a redox-active drug candidate. MnHex crosses the blood–brain barrier, and improved neurologic outcome and decreased infarct size and inflammation in a rat middle cerebral artery occlusion (MCAO) ischemic stroke model. Yet, the dose and the therapeutic efficacy of Mn porphyrin were limited by an adverse effect of arterial hypotension. An equally lipophilic Fe analog, (OH)FeTnHex-2-PyP4+ (FeHex), is as redox-active and potent SOD mimic in vitro. With different coordination geometry of the metal site, FeHex has one hydroxo (OH) ligand (instead of water) bound to the Fe center in the axial position. It has ~2 orders of magnitude higher efficacy than MnHex in an SOD-deficient E. coli model of oxidative stress. In vivo, it does not cause arterial hypotension and is less toxic to mice. We thus evaluated FeHex versus MnHex in a rodent MCAO model. We first performed short- and long-term pharmacokinetics (PK) of both porphyrins in the plasma, brain, and liver of rats and mice. Given that damage to the brain during stroke occurs very rapidly, fast delivery of a sufficient dose of drug is important. Therefore, we aimed to demonstrate if, and how fast after reperfusion, Fe porphyrin reaches the brain relative to the Mn analog. A markedly different plasma half-life was found with FeHex (~23 h) than with MnHex (~1.4 h), which resulted in a more than 2-fold higher plasma exposure (AUC) in a 7-day twice-daily treatment of rats. The increased plasma half-life is explained by the much lower liver retention of FeHex than typically found in Mn analogs. In the brain, a 3-day mouse PK study showed similar levels of MnHex and FeHex. The same result was obtained in a 7-day rat PK study, despite the higher plasma exposure of FeHex. Importantly, in a short-term PK study with treatment starting 2 h post MCAO, both Fe- and Mn- analogs distributed at a higher level to the injured brain hemisphere, with a more pronounced effect observed with FeHex. While a 3-day mouse MCAO study suggested the efficacy of Fe porphyrin, in a 7-day rat MCAO study, Mn-, but not Fe porphyrin, was efficacious. The observed lack of FeHex efficacy was discussed in terms of significant differences in the chemistry of Fe vs. the Mn center of metalloporphyrin; relative to MnHex, FeHex has the propensity for axial coordination, which in vivo would preclude the reactivity of the Fe center towards small reactive species. Full article
(This article belongs to the Special Issue Catalytic Antioxidants)
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Review

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22 pages, 33527 KiB  
Review
Selenium-Catalyzed Reduction of Hydroperoxides in Chemistry and Biology
by Laura Orian and Leopold Flohé
Antioxidants 2021, 10(10), 1560; https://doi.org/10.3390/antiox10101560 - 30 Sep 2021
Cited by 17 | Viewed by 2568
Abstract
Among the chalcogens, selenium is the key element for catalyzed H2O2 reduction. In organic synthesis, catalytic amounts of organo mono- and di-selenides are largely used in different classes of oxidations, in which H2O2 alone is poorly efficient. [...] Read more.
Among the chalcogens, selenium is the key element for catalyzed H2O2 reduction. In organic synthesis, catalytic amounts of organo mono- and di-selenides are largely used in different classes of oxidations, in which H2O2 alone is poorly efficient. Biological hydroperoxide metabolism is dominated by peroxidases and thioredoxin reductases, which balance hydroperoxide challenge and contribute to redox regulation. When their selenocysteine is replaced by cysteine, the cellular antioxidant defense system is impaired. Finally, classes of organoselenides have been synthesized with the aim of mimicking the biological strategy of glutathione peroxidases, but their therapeutic application has so far been limited. Moreover, their therapeutic use may be doubted, because H2O2 is not only toxic but also serves as an important messenger. Therefore, over-optimization of H2O2 reduction may lead to unexpected disturbances of metabolic regulation. Common to all these systems is the nucleophilic attack of selenium to one oxygen of the peroxide bond promoting its disruption. In this contribution, we revisit selected examples from chemistry and biology, and, by using results from accurate quantum mechanical modelling, we provide an accurate unified picture of selenium’s capacity of reducing hydroperoxides. There is clear evidence that the selenoenzymes remain superior in terms of catalytic efficiency. Full article
(This article belongs to the Special Issue Catalytic Antioxidants)
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21 pages, 691 KiB  
Review
Catalytic Antioxidants in the Kidney
by Yu Ah Hong and Cheol Whee Park
Antioxidants 2021, 10(1), 130; https://doi.org/10.3390/antiox10010130 - 18 Jan 2021
Cited by 33 | Viewed by 6067
Abstract
Reactive oxygen species and reactive nitrogen species are highly implicated in kidney injuries that include acute kidney injury, chronic kidney disease, hypertensive nephropathy, and diabetic nephropathy. Therefore, antioxidant agents are promising therapeutic strategies for kidney diseases. Catalytic antioxidants are defined as small molecular [...] Read more.
Reactive oxygen species and reactive nitrogen species are highly implicated in kidney injuries that include acute kidney injury, chronic kidney disease, hypertensive nephropathy, and diabetic nephropathy. Therefore, antioxidant agents are promising therapeutic strategies for kidney diseases. Catalytic antioxidants are defined as small molecular mimics of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, and some of them function as potent detoxifiers of lipid peroxides and peroxynitrite. Several catalytic antioxidants have been demonstrated to be effective in a variety of in vitro and in vivo disease models that are associated with oxidative stress, including kidney diseases. This review summarizes the evidence for the role of antioxidant enzymes in kidney diseases, the classifications of catalytic antioxidants, and their current applications to kidney diseases. Full article
(This article belongs to the Special Issue Catalytic Antioxidants)
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16 pages, 1551 KiB  
Review
Pro-Aging Effects of Xanthine Oxidoreductase Products
by Maria Giulia Battelli, Massimo Bortolotti, Andrea Bolognesi and Letizia Polito
Antioxidants 2020, 9(9), 839; https://doi.org/10.3390/antiox9090839 - 08 Sep 2020
Cited by 17 | Viewed by 5899
Abstract
The senescence process is the result of a series of factors that start from the genetic constitution interacting with epigenetic modifications induced by endogenous and environmental causes and that lead to a progressive deterioration at the cellular and functional levels. One of the [...] Read more.
The senescence process is the result of a series of factors that start from the genetic constitution interacting with epigenetic modifications induced by endogenous and environmental causes and that lead to a progressive deterioration at the cellular and functional levels. One of the main causes of aging is oxidative stress deriving from the imbalance between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their scavenging through antioxidants. Xanthine oxidoreductase (XOR) activities produce uric acid, as well as reactive oxygen and nitrogen species, which all may be relevant to such equilibrium. This review analyzes XOR activity through in vitro experiments, animal studies and clinical reports, which highlight the pro-aging effects of XOR products. However, XOR activity contributes to a regular level of ROS and RNS, which appears essential for the proper functioning of many physiological pathways. This discourages the use of therapies with XOR inhibitors, unless symptomatic hyperuricemia is present. Full article
(This article belongs to the Special Issue Catalytic Antioxidants)
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