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Chemistry, Biology and Pharmacology of Modulators of Oxidative Stress
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Chemistry, Biology and Pharmacology of Modulators of Oxidative Stress

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (15 February 2024) | Viewed by 52745

Special Issue Editors

Prof. Dr. Luciano Saso

grade E-Mail Website
Guest Editor
Faculty of Pharmacy and Medicine, Sapienza University of Rome, 00185 Rome, Italy
Interests: pharmacology; therapeutic modulators of oxidative stress
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Grzegorz Wegrzyn

E-Mail Website
Guest Editor
Depratment of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland
Interests: regulation of DNA replication; control of gene expression; oxidative stress in bacterial virulence; molecular mechanisms of mucopolysaccharidoses; development of novel therapeutic options
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jelena Kotur-Stevuljević

E-Mail Website
Guest Editor
Department for Medical BiochemistryFaculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Interests: oxidative stress related to atherosclerosis and cancer, antioxidative/prooxidative potency of different substances and newly-sinthesized drugs characterisation

Special Issue Information

Dear Colleagues,

Reactive oxygen (ROS), nitrogen (RNS), and sulfur (RSS) species are implicated in the pathogenesis of a variety of pathological conditions, including chronic infections (such as HIV-1), inflammatory disorders, cardiovascular diseases, neurodegenerative diseases, and cancer. Unfortunately, antioxidant therapies did not prove to be effective in most of the clinical studies for different reasons. However, modulation of oxidative stress, particularly through activation or inhibition of Nrf2, is considered an important strategy for the development of new drugs for some of the aforementioned pathologies such as cardiovascular and neoplastic diseases resistant to other treatments, and also HIV infection. The main aim of this Special Issue is to address different chemical, biological, and pharmacological aspects of research on the modulation of oxidative stress. The HIV virus has the potential to inhibit the Nrf2/ARE pathway during replication, which leads to oxidative stress generation. Activation of the Nrf2/ARE signaling pathway could be a target for therapeutic intervention in HIV-infected patients. Potential topics include but are not limited to the following:

  • Synthesis and derivatization of oxidative stress modulators with potential pharmacological applications, to optimize their antioxidant properties and bioavailability;
  • In vitro and in vivo studies of antioxidant properties of synthetic, semi-synthetic and natural compounds
  • Synthesis of new conjugates using oxidative systems for different medical fields improvement (MRI, PET and other imaging techniques-related fields) in order to enhance precision medicine in a future;
  • Nonradical scavenging mechanisms of action of oxidative stress modulators with special attention to the Keap1/Nrf2/ARE signaling pathway;
  • Pharmacokinetics, metabolic pathways, and antioxidant activity of metabolites;
  • In vitro and in vivo studies on the pharmacological activity of oxidative stress modulators;
  • Relevant biological markers to assess in vivo antioxidant/prooxidant action and its correlation with clinical efficacy;
  • Oxidative stress and antioxidants in neurodegeneration, genetic, and infectious diseases—from mechanisms of action to potential therapies.

Selected references

Bloch S, Nejman-Faleńczyk B, Pierzynowska K, Piotrowska E, Węgrzyn A, Marminon C, Bouaziz Z, Nebois P, Jose J, Le Borgne M, Saso L, Węgrzyn G. Inhibition of Shiga toxin-converting bacteriophage development by novel antioxidant compounds. J Enzyme Inhib Med Chem. 2018 Dec;33(1):639-650.

Firuzi O, Miri R, Tavakkoli M, Saso L. Antioxidant therapy: current status and future prospects. Curr Med Chem. 2011;18(25):3871-88.

Giorgi C et al. 2018 Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases. Int Rev Cell Mol Biol. 2018;340: 209-344.

Gjorgieva-Ackova D, Kotur-Stevuljevic J, Mishra Bhushan C, Luthra Mehta P, Saso L. Antioxidant properties of synthesized bicyclic thiazolopyrimidine derivatives as possible therapeutic agents. Appl Sci-Basel 2019; 9(1)113; doi:10.3390/app9010113

Ivanov AV et al. Oxidative Stress during HIV Infection: mechanisms and consequences. Oxid Med Cell Longev. 2016 http://dx.doi.org/10.1155/2016/8910396

Panieri E, Saso L. Potential Applications of NRF2 Inhibitors in Cancer Therapy. Oxid Med Cell Longev. 2019

Ramezani A, Parsa Nahad M, Faghihloo E. The role of Nrf2 transcription factor in viral infection. J Cell Biochem. 2018;119:6366–6382

Saso L, Firuzi O. Pharmacological applications of antioxidants: lights and shadows. Curr Drug Targets. 2014;15(13):1177-99.

Sova M, Saso L. Design and development of Nrf2 modulators for cancer chemoprevention and therapy: a review. Drug Des Devel Ther. 2018;12:3181-3197

Telkoparan-Akillilar P, Suzen S, Saso L. Pharmacological Applications of Nrf2 Inhibitors as Potential Antineoplastic Drugs. Int J Mol Sci. 2019;20(8).

Prof. Dr. Luciano Saso
Prof. Dr. Grzegorz Wegrzyn
Prof. Jelena Kotur-Stevuljević
Guest Editors

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.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 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

  • Oxidative stress
  • Antioxidants
  • Pro-oxidants
  • Nrf2
  • Cancer therapy
  • HIV therapy

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Related Special Issues

Published Papers (5 papers)

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Research

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12 pages, 1399 KiB  
Article
Novel Strategy for Non-Aqueous Bioconjugation of Substituted Phenyl-1,2,4-triazole-3,5-dione Analogues
by Hugh G. Hiscocks, Alison T. Ung and Giancarlo Pascali
Molecules 2022, 27(19), 6667; https://doi.org/10.3390/molecules27196667 - 7 Oct 2022
Cited by 1 | Viewed by 1974
Abstract
A novel 4-[4-(pentafluoro-λ⁶-sulfanyl)phenyl]-1,2,4-triazole-3,5-dione (5a) was synthesised as a potential [18F]radio-prosthetic group for radiolabelling peptides and proteins via selective bioconjugation with the phenolic side chains of tyrosine residues. Preliminary conjugation tests revealed the rapid hydrolysis of 5a under semi-aqueous conditions; [...] Read more.
A novel 4-[4-(pentafluoro-λ⁶-sulfanyl)phenyl]-1,2,4-triazole-3,5-dione (5a) was synthesised as a potential [18F]radio-prosthetic group for radiolabelling peptides and proteins via selective bioconjugation with the phenolic side chains of tyrosine residues. Preliminary conjugation tests revealed the rapid hydrolysis of 5a under semi-aqueous conditions; these results led to further investigation into the electronic substituent effects of PTAD derivatives and corresponding hydrolytic stabilities. Five derivatives of 5a with para substituents of varying electron donating and withdrawing effects were synthesised for the investigation. The bioconjugation of these derivatives with model tyrosine was monitored in both aqueous and organic media in the presence of a variety of catalysts. From these investigations, we have found HFIP to be an effective catalyst when used in tandem with DCM as a solvent to give PTAD-tyrosine conjugate products (6a–f) in satisfactory to good yields (54–79%), whereas analogous reactions performed in acetonitrile were unsuccessful. The discovery of this system has allowed for the successful conjugation of electron-deficient PTAD derivatives to tyrosine, which would otherwise be unachievable under aqueous reaction conditions. The inclusion of these electron-deficient, fluorinated PTAD derivatives for use in the PTAD-tyrosine conjugation will hopefully broaden their applicability within fields such as 19F-MRI and PET imaging. Full article
(This article belongs to the Special Issue Chemistry, Biology and Pharmacology of Modulators of Oxidative Stress)
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13 pages, 4185 KiB  
Article
A Novel 5-Chloro-N-phenyl-1H-indole-2-carboxamide Derivative as Brain-Type Glycogen Phosphorylase Inhibitor: Potential Therapeutic Effect on Cerebral Ischemia
by Yatao Huang, Shuai Li, Youde Wang, Zhiwei Yan, Yachun Guo and Liying Zhang
Molecules 2022, 27(19), 6333; https://doi.org/10.3390/molecules27196333 - 26 Sep 2022
Cited by 5 | Viewed by 1726
Abstract
Brain-type glycogen phosphorylase inhibitors are potential new drugs for treating ischemic brain injury. In our previous study, we reported compound 1 as a novel brain-type glycogen phosphorylase inhibitor with cardioprotective properties. We also found that compound 1 has high blood–brain barrier permeability through [...] Read more.
Brain-type glycogen phosphorylase inhibitors are potential new drugs for treating ischemic brain injury. In our previous study, we reported compound 1 as a novel brain-type glycogen phosphorylase inhibitor with cardioprotective properties. We also found that compound 1 has high blood–brain barrier permeability through the ADMET prediction website. In this study, we deeply analyzed the protective effect of compound 1 on hypoxic-ischemic brain injury, finding that compound 1 could alleviate the hypoxia/reoxygenation (H/R) injury of astrocytes by improving cell viability and reducing LDH leakage rate, intracellular glucose content, and post-ischemic ROS level. At the same time, compound 1 could reduce the level of ATP in brain cells after ischemia, improve cellular energy metabolism, downregulate the degree of extracellular acidification, and improve metabolic acidosis. It could also increase the level of mitochondrial aerobic energy metabolism during brain cell reperfusion, reduce anaerobic glycolysis, and inhibit apoptosis and the expression of apoptosis-related proteins. The above results indicated that compound 1 is involved in the regulation of glucose metabolism, can control cell apoptosis, and has protective and potential therapeutic effects on cerebral ischemia-reperfusion injury, which provides a new reference and possibility for the development of novel drugs for the treatment of ischemic brain injury. Full article
(This article belongs to the Special Issue Chemistry, Biology and Pharmacology of Modulators of Oxidative Stress)
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Review

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22 pages, 783 KiB  
Review
Malondialdehyde as a Potential Oxidative Stress Marker for Allergy-Oriented Diseases: An Update
by Raffaele Cordiano, Mario Di Gioacchino, Rocco Mangifesta, Claudia Panzera, Sebastiano Gangemi and Paola Lucia Minciullo
Molecules 2023, 28(16), 5979; https://doi.org/10.3390/molecules28165979 - 9 Aug 2023
Cited by 54 | Viewed by 15393
Abstract
Malondialdehyde (MDA) is a compound that is derived from the peroxidation of polyunsaturated fatty acids. It has been used as a biomarker to measure oxidative stress in various biological samples in patients who are affected by a wide range of diseases. The aim [...] Read more.
Malondialdehyde (MDA) is a compound that is derived from the peroxidation of polyunsaturated fatty acids. It has been used as a biomarker to measure oxidative stress in various biological samples in patients who are affected by a wide range of diseases. The aim of our work is to provide an updated overview of the role of MDA as a marker of oxidative stress in allergy-related diseases. We considered studies involving both paediatric and adult patients affected by rhinitis, asthma, urticaria and atopic dermatitis. The measurement of MDA was performed on different types of samples. The reported data highlight the role of serum MDA in inflammatory airway diseases. According to the literature review, the oxidative stress status in asthmatic patients, assessed via MDA determination, appears to worsen in the presence of other allergic airway diseases and in relation to the disease severity. This suggests that MDA can be a suitable marker for monitoring the disease status. However, there are several limitations in the considered studies due to the different samples used and the lack of phenotyping and description of the clinical period of patients examined. In cutaneous allergic diseases, the role of MDA is controversial because of the smallness of the studies and the heterogeneity of the samples and patients. Full article
(This article belongs to the Special Issue Chemistry, Biology and Pharmacology of Modulators of Oxidative Stress)
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16 pages, 1431 KiB  
Review
Hydrogen Sulfide: Novel Endogenous and Exogenous Modulator of Oxidative Stress in Retinal Degeneration Diseases
by Panpan Li, Hanhan Liu, Xin Shi and Verena Prokosch
Molecules 2021, 26(9), 2411; https://doi.org/10.3390/molecules26092411 - 21 Apr 2021
Cited by 19 | Viewed by 2970
Abstract
Oxidative stress (OS) damage can cause significant injury to cells, which is related to the occurrence and development of many diseases. This pathological process is considered to be the first step to trigger the death of outer retinal neurons, which is related to [...] Read more.
Oxidative stress (OS) damage can cause significant injury to cells, which is related to the occurrence and development of many diseases. This pathological process is considered to be the first step to trigger the death of outer retinal neurons, which is related to the pathology of retinal degenerative diseases. Hydrogen sulfide (H2S) has recently received widespread attention as a physiological signal molecule and gas neuromodulator and plays an important role in regulating OS in eyes. In this article, we reviewed the OS responses and regulatory mechanisms of H2S and its donors as endogenous and exogenous regulators in retinal degenerative diseases. Understanding the relevant mechanisms will help to identify the therapeutic potential of H2S in retinal degenerative diseases. Full article
(This article belongs to the Special Issue Chemistry, Biology and Pharmacology of Modulators of Oxidative Stress)
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31 pages, 1504 KiB  
Review
An Overview of Nrf2 Signaling Pathway and Its Role in Inflammation
by Sarmistha Saha, Brigitta Buttari, Emiliano Panieri, Elisabetta Profumo and Luciano Saso
Molecules 2020, 25(22), 5474; https://doi.org/10.3390/molecules25225474 - 23 Nov 2020
Cited by 745 | Viewed by 28042
Abstract
Inflammation is a key driver in many pathological conditions such as allergy, cancer, Alzheimer’s disease, and many others, and the current state of available drugs prompted researchers to explore new therapeutic targets. In this context, accumulating evidence indicates that the transcription factor Nrf2 [...] Read more.
Inflammation is a key driver in many pathological conditions such as allergy, cancer, Alzheimer’s disease, and many others, and the current state of available drugs prompted researchers to explore new therapeutic targets. In this context, accumulating evidence indicates that the transcription factor Nrf2 plays a pivotal role controlling the expression of antioxidant genes that ultimately exert anti-inflammatory functions. Nrf2 and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH- associated protein 1 (Keap1), play a central role in the maintenance of intracellular redox homeostasis and regulation of inflammation. Interestingly, Nrf2 is proved to contribute to the regulation of the heme oxygenase-1 (HO-1) axis, which is a potent anti-inflammatory target. Recent studies showed a connection between the Nrf2/antioxidant response element (ARE) system and the expression of inflammatory mediators, NF-κB pathway and macrophage metabolism. This suggests a new strategy for designing chemical agents as modulators of Nrf2 dependent pathways to target the immune response. Therefore, the present review will examine the relationship between Nrf2 signaling and the inflammation as well as possible approaches for the therapeutic modulation of this pathway. Full article
(This article belongs to the Special Issue Chemistry, Biology and Pharmacology of Modulators of Oxidative Stress)
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