Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress
Oxidative stress is associated with the increased production of reactive oxygen species or with a significant decrease in the effectiveness of antioxidant enzymes and nonenzymatic defense. The penetration of oxygen and free radicals in the hydrophobic interior of biological membranes initiates radic...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/4/624 |
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| author | Vessela D. Kancheva Maria Antonietta Dettori Davide Fabbri Petko Alov Silvia E. Angelova Adriana K. Slavova-Kazakova Paola Carta Valerii A. Menshov Olga I. Yablonskaya Aleksei V. Trofimov Ivanka Tsakovska Luciano Saso |
| author_facet | Vessela D. Kancheva Maria Antonietta Dettori Davide Fabbri Petko Alov Silvia E. Angelova Adriana K. Slavova-Kazakova Paola Carta Valerii A. Menshov Olga I. Yablonskaya Aleksei V. Trofimov Ivanka Tsakovska Luciano Saso |
| author_sort | Vessela D. Kancheva |
| collection | DOAJ |
| description | Oxidative stress is associated with the increased production of reactive oxygen species or with a significant decrease in the effectiveness of antioxidant enzymes and nonenzymatic defense. The penetration of oxygen and free radicals in the hydrophobic interior of biological membranes initiates radical disintegration of the hydrocarbon “tails” of the lipids. This process is known as “lipid peroxidation”, and the accumulation of the oxidation products as peroxides and the aldehydes and acids derived from them are often used as a measure of oxidative stress levels. In total, 40 phenolic antioxidants were selected for a comparative study and analysis of their chain-breaking antioxidant activity, and thus as modulators of oxidative stress. This included natural and natural-like <i>ortho</i>-methoxy and <i>ortho</i>-hydroxy phenols, nine of them newly synthesized. Applied experimental and theoretical methods (bulk lipid autoxidation, chemiluminescence, in silico methods such as density functional theory (DFT) and quantitative structure–activity relationship ((Q)SAR) modeling) were used to clarify their structure–activity relationship. Kinetics of non-inhibited and inhibited lipid oxidation in close connection with inhibitor transformation under oxidative stress is considered. Special attention has been paid to chemical reactions resulting in the initiation of free radicals, a key stage of oxidative stress. Effects of substituents in the side chains and in the phenolic ring of hydroxylated phenols and biphenols, and the concentration were discussed. |
| first_indexed | 2024-03-10T12:11:02Z |
| format | Article |
| id | doaj.art-e144caa84f97472b878fdb3166d5448e |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T12:11:02Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-e144caa84f97472b878fdb3166d5448e2023-11-21T16:12:51ZengMDPI AGAntioxidants2076-39212021-04-0110462410.3390/antiox10040624Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative StressVessela D. Kancheva0Maria Antonietta Dettori1Davide Fabbri2Petko Alov3Silvia E. Angelova4Adriana K. Slavova-Kazakova5Paola Carta6Valerii A. Menshov7Olga I. Yablonskaya8Aleksei V. Trofimov9Ivanka Tsakovska10Luciano Saso11Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., bl.9, 1113 Sofia, BulgariaCNR, Istituto di Chimica Biomolecolare, Traversa La Crucca 3, 07100 Sassari, ItalyCNR, Istituto di Chimica Biomolecolare, Traversa La Crucca 3, 07100 Sassari, ItalyInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., bl.21, 1113 Sofia, BulgariaInstitute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., bl.109, 1113 Sofia, BulgariaInstitute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., bl.9, 1113 Sofia, BulgariaCNR, Istituto di Chimica Biomolecolare, Traversa La Crucca 3, 07100 Sassari, ItalyEmanuel Institute of Biochemical Physics, Russian Academy of Sciences, “Kosigina”4 Str., 119334 Moscow, RussiaEmanuel Institute of Biochemical Physics, Russian Academy of Sciences, “Kosigina”4 Str., 119334 Moscow, RussiaEmanuel Institute of Biochemical Physics, Russian Academy of Sciences, “Kosigina”4 Str., 119334 Moscow, RussiaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., bl.21, 1113 Sofia, BulgariaDepartment of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University, P.le Aldo Moro 5, 00185 Rome, ItalyOxidative stress is associated with the increased production of reactive oxygen species or with a significant decrease in the effectiveness of antioxidant enzymes and nonenzymatic defense. The penetration of oxygen and free radicals in the hydrophobic interior of biological membranes initiates radical disintegration of the hydrocarbon “tails” of the lipids. This process is known as “lipid peroxidation”, and the accumulation of the oxidation products as peroxides and the aldehydes and acids derived from them are often used as a measure of oxidative stress levels. In total, 40 phenolic antioxidants were selected for a comparative study and analysis of their chain-breaking antioxidant activity, and thus as modulators of oxidative stress. This included natural and natural-like <i>ortho</i>-methoxy and <i>ortho</i>-hydroxy phenols, nine of them newly synthesized. Applied experimental and theoretical methods (bulk lipid autoxidation, chemiluminescence, in silico methods such as density functional theory (DFT) and quantitative structure–activity relationship ((Q)SAR) modeling) were used to clarify their structure–activity relationship. Kinetics of non-inhibited and inhibited lipid oxidation in close connection with inhibitor transformation under oxidative stress is considered. Special attention has been paid to chemical reactions resulting in the initiation of free radicals, a key stage of oxidative stress. Effects of substituents in the side chains and in the phenolic ring of hydroxylated phenols and biphenols, and the concentration were discussed.https://www.mdpi.com/2076-3921/10/4/624oxidative stressbio-antioxidantchain breaking antioxidant activitystructure–activity relationshipsynthesis |
| spellingShingle | Vessela D. Kancheva Maria Antonietta Dettori Davide Fabbri Petko Alov Silvia E. Angelova Adriana K. Slavova-Kazakova Paola Carta Valerii A. Menshov Olga I. Yablonskaya Aleksei V. Trofimov Ivanka Tsakovska Luciano Saso Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress Antioxidants oxidative stress bio-antioxidant chain breaking antioxidant activity structure–activity relationship synthesis |
| title | Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress |
| title_full | Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress |
| title_fullStr | Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress |
| title_full_unstemmed | Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress |
| title_short | Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress |
| title_sort | natural chain breaking antioxidants and their synthetic analogs as modulators of oxidative stress |
| topic | oxidative stress bio-antioxidant chain breaking antioxidant activity structure–activity relationship synthesis |
| url | https://www.mdpi.com/2076-3921/10/4/624 |
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