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Review

Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine

by
Viktor A. Timoshnikov
1,*,
Olga Yu. Selyutina
1,
Nikolay E. Polyakov
1,
Victoria Didichenko
2 and
George J. Kontoghiorghes
2,*
1
Institute of Chemical Kinetics & Combustion, 630090 Novosibirsk, Russia
2
Postgraduate Research Institute of Science, Technology, Environment and Medicine, Limassol 3021, Cyprus
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(3), 1247; https://doi.org/10.3390/ijms23031247
Submission received: 29 December 2021 / Revised: 13 January 2022 / Accepted: 20 January 2022 / Published: 23 January 2022
(This article belongs to the Special Issue Advances on Chelation and Chelator Metal Complexes in Medicine)
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Abstract

The antioxidant/pro-oxidant activity of drugs and dietary molecules and their role in the maintenance of redox homeostasis, as well as the implications in health and different diseases, have not yet been fully evaluated. In particular, the redox activity and other interactions of drugs with essential redox metal ions, such as iron and copper, need further investigation. These metal ions are ubiquitous in human nutrition but also widely found in dietary supplements and appear to exert major effects on redox homeostasis in health, but also on many diseases of free radical pathology. In this context, the redox mechanistic insights of mainly three prototype groups of drugs, namely alpha-ketohydroxypyridines (alpha-hydroxypyridones), e.g., deferiprone, anthraquinones, e.g., doxorubicin and thiosemicarbazones, e.g., triapine and their metal complexes were examined; details of the mechanisms of their redox activity were reviewed, with emphasis on the biological implications and potential clinical applications, including anticancer activity. Furthermore, the redox properties of these three classes of chelators were compared to those of the iron chelating drugs and also to vitamin C, with an emphasis on their potential clinical interactions and future clinical application prospects in cancer, neurodegenerative and other diseases.
Keywords: chelators; transition metals; reactive oxygen species; antioxidant activity; pro-oxidant activity; alpha-ketohydroxypyridines; hydroxypyridones; anthraquinones; thiosemicarbazones; ascorbic acid chelators; transition metals; reactive oxygen species; antioxidant activity; pro-oxidant activity; alpha-ketohydroxypyridines; hydroxypyridones; anthraquinones; thiosemicarbazones; ascorbic acid

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MDPI and ACS Style

Timoshnikov, V.A.; Selyutina, O.Y.; Polyakov, N.E.; Didichenko, V.; Kontoghiorghes, G.J. Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine. Int. J. Mol. Sci. 2022, 23, 1247. https://doi.org/10.3390/ijms23031247

AMA Style

Timoshnikov VA, Selyutina OY, Polyakov NE, Didichenko V, Kontoghiorghes GJ. Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine. International Journal of Molecular Sciences. 2022; 23(3):1247. https://doi.org/10.3390/ijms23031247

Chicago/Turabian Style

Timoshnikov, Viktor A., Olga Yu. Selyutina, Nikolay E. Polyakov, Victoria Didichenko, and George J. Kontoghiorghes. 2022. "Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine" International Journal of Molecular Sciences 23, no. 3: 1247. https://doi.org/10.3390/ijms23031247

APA Style

Timoshnikov, V. A., Selyutina, O. Y., Polyakov, N. E., Didichenko, V., & Kontoghiorghes, G. J. (2022). Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine. International Journal of Molecular Sciences, 23(3), 1247. https://doi.org/10.3390/ijms23031247

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