Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine
Abstract
:1. Introduction
2. The Role of Essential Transition Metals in Living Systems
3. The Potential Antioxidant/Pro-Oxidant Effects of Ascorbic Acid
4. Redox Properties and Biological Implications of Chelating Drugs
5. Alpha-Ketohydroxypyridine Chelators
6. Anthraquinone Chelators
7. Thiosemicarbazone Chelators
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
Abeta | anti-amyloid beta aggregation; |
AChE | anti-acetylcholinesterase; |
anti-Aβ | inhibition of amyloid plaque deposits; |
AoA | antioxidant activity; |
Asc•− | ascorbyl anion radical; |
AscH2 | ascorbic acid; |
AscH• | ascorbyl radical; |
AscH− | ascorbate anion; |
CIDNP | chemically induced dynamic nuclear polarization; |
Dox | Doxorubicin; |
DpC | di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone; |
DHA | dehydroascorbate; |
DHP | dihydropyridine; |
DNA | deoxyribonucleic acid; |
Dp44mT | di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone; |
EPR | electron paramagnetic resonance; |
GSH | glutathione; |
HL1 | 2-((E)-3-(4-chlorophenyl)-1-phenylallylidene)-N-phenyl-hydrazinecarbothioamide; |
HL4 | 2-((E)-3-(4-cyanophenyl)-1-phenylallylidene)-N-phenyl-hydrazinecarbothioamide; |
H2O2 | hydrogen peroxide; |
H3Ra | H3 receptor antagonism; |
IND | investigational new drugs; |
KHP | alpha-ketohydroxypyridines; |
LA | linoleic acid; |
logP | octanol/water partition coefficient; |
L1 | deferiprone; |
NADH | nicotinamide adenine dinucleotide; |
NMR | nuclear magnetic resonance; |
1O2 | singlet oxygen; |
OH | hydroxyl radical; |
OOH | peroxyl radical; |
Q1 | 2-phenyl-4-(butylamino)naphtho[2,3-h] quinoline-7,12-dione; |
Q−• | semiquinone radical; |
RNA | ribonucleic acid; |
ROS | reactive oxygen species; |
TSC | thiosemicarbazone; |
UV-Vis | ultraviolet-visible. |
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Radical | k (M−1s−1) |
---|---|
•OH (hydroxyl) | 1.1 × 1010 |
RO• (tert-butyl alkoxyl radical) | 1.6 × 109 |
ROO• (alkyl peroxyl radical, e.g., CH3OO•) | 1–2 × 106 |
GS• (glutathiol radical) | 6 × 108 |
TO• (tocopheroxyl radical) | 2 × 105 |
Asc•− (dismutation) | 2 × 105 |
O2•−/•OOH | 1 × 105 |
Chelator | Types of Anti-Alzheimer Activity | References * | |
---|---|---|---|
| R1,R2 = H, | AoA AChE Abeta | [117] |
| n = 2–4 R1 = H, Bn R2 = H, OCH3 | AoA AChE Abeta | [167,168] |
| n = 3–5 NR1R2 = NR1R2 = | AoA Abeta H3Ra | [169,170] |
| n = 1 X,Y = -CH2Ph, -Ph, -(CH2)n n = 0 X = Ph R = H, Bn | AoA AChE Abeta | [117,171] |
| n = 1–3 R = t-Bu, OCH3 | AoA | [139] |
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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
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 StyleTimoshnikov, 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