Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress
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
Affiliations
Vessela D. Kancheva
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., bl.9, 1113 Sofia, Bulgaria
Maria Antonietta Dettori
CNR, Istituto di Chimica Biomolecolare, Traversa La Crucca 3, 07100 Sassari, Italy
Davide Fabbri
CNR, Istituto di Chimica Biomolecolare, Traversa La Crucca 3, 07100 Sassari, Italy
Petko Alov
Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., bl.21, 1113 Sofia, Bulgaria
Silvia E. Angelova
Institute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., bl.109, 1113 Sofia, Bulgaria
Adriana K. Slavova-Kazakova
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., bl.9, 1113 Sofia, Bulgaria
Paola Carta
CNR, Istituto di Chimica Biomolecolare, Traversa La Crucca 3, 07100 Sassari, Italy
Valerii A. Menshov
Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, “Kosigina”4 Str., 119334 Moscow, Russia
Olga I. Yablonskaya
Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, “Kosigina”4 Str., 119334 Moscow, Russia
Aleksei V. Trofimov
Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, “Kosigina”4 Str., 119334 Moscow, Russia
Ivanka Tsakovska
Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., bl.21, 1113 Sofia, Bulgaria
Luciano Saso
Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy
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 ortho-methoxy and ortho-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.
