Therapeutic Perspective of Vitamin C and Its Derivatives

Macan, Andrijana Meščić; Kraljević, Tatjana Gazivoda; Raić‐Malić, Silvana

doi:10.3390/antiox8080247

Cited by 99 publications

(58 citation statements)

References 131 publications

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“…Vitamin E helps to protect the cell by inhibiting lipid peroxidation (57). Vitamin C reacts with •O2- and •OH to form the dehydroascorbic acid (58). Hyperglycemia leads to the reduction of vitamin E and vitamin C even their dietary intake is normal (59).…”

Section: Possible Mechanisms Mediated By Glucose Fluctuationsmentioning

confidence: 99%

Molecular Mechanisms of Glucose Fluctuations on Diabetic Complications

et al. 2019

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Accumulating evidence indicates the occurrence and development of diabetic complications relates to not only constant high plasma glucose, but also glucose fluctuations which affect various kinds of molecular mechanisms in various target cells and tissues. In this review, we detail reactive oxygen species and their potentially damaging effects upon glucose fluctuations and resultant downstream regulation of protein signaling pathways, including protein kinase C, protein kinase B, nuclear factor-κB, and the mitogen-activated protein kinase signaling pathway. A deeper understanding of glucose-fluctuation-related molecular mechanisms in the development of diabetic complications may enable more potential target therapies in future.

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Section: Possible Mechanisms Mediated By Glucose Fluctuationsmentioning

confidence: 99%

Molecular Mechanisms of Glucose Fluctuations on Diabetic Complications

et al. 2019

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“…However, the evidence that ascorbic acid could help human cancer patients is still thin and requires additional study. The results of published studies fail to prove that there is a clinically relevant positive effect of ascorbic acid supplementation in cancer patients in general on the overall survival, clinical status, quality of life and performance status [1,14,26].…”

Section: Introductionmentioning

confidence: 98%

“…Vitamin C or ascorbic acid (AscH 2 , Scheme 1) is a powerful water-soluble antioxidant, found in nature and present in fresh fruit and vegetables [1][2][3]. Ascorbic acid is also known as a reducing agent and a radical scavenger.…”

Section: Introductionmentioning

confidence: 99%

Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone

Timoshnikov

Kobzeva

Polyakov

et al. 2020

IJMS

108

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Ascorbic acid (AscH2) is one of the most important vitamins found in the human diet, with many biological functions including antioxidant, chelating, and coenzyme activities. Ascorbic acid is also widely used in medical practice especially for increasing iron absorption and as an adjuvant therapeutic in iron chelation therapy, but its mode of action and implications in iron metabolism and toxicity are not yet clear. In this study, we used UV–Vis spectrophotometry, NMR spectroscopy, and EPR spin trapping spectroscopy to investigate the antioxidant/pro-oxidant effects of ascorbic acid in reactions involving iron and the iron chelator deferiprone (L1). The experiments were carried out in a weak acidic (pH from 3 to 5) and neutral (pH 7.4) medium. Ascorbic acid exhibits predominantly pro-oxidant activity by reducing Fe3+ to Fe2+, followed by the formation of dehydroascorbic acid. As a result, ascorbic acid accelerates the redox cycle Fe3+ ↔ Fe2+ in the Fenton reaction, which leads to a significant increase in the yield of toxic hydroxyl radicals. The analysis of the experimental data suggests that despite a much lower stability constant of the iron–ascorbate complex compared to the FeL13 complex, ascorbic acid at high concentrations is able to substitute L1 in the FeL13 chelate complex resulting in the formation of mixed L12AscFe complex. This mixed chelate complex is redox stable at neutral pH = 7.4, but decomposes at pH = 4–5 during several minutes at sub-millimolar concentrations of ascorbic acid. The proposed mechanisms play a significant role in understanding the mechanism of action, pharmacological, therapeutic, and toxic effects of the interaction of ascorbic acid, iron, and L1.

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“…Vitamin C (L-ascorbic acid, L-ASA) or more accurately the ascorbate anion (A, Figure 2), is an excellent reducing agent and a powerful antioxidant co-factor required for key enzyme reactions [10,11,12,13,14]. Due to the low one electron reduction potential of the ascorbate radical (RA)/ascorbate (A) couple (Figure 2), almost every oxidizing radical formed in the biological system, including the hydroxyl (HO • ), alkoxyl, peroxyl, thiol, and tocopheroxyl radicals cause one-electron oxidation of the ascorbate anion, resulting in the formation of the resonance stabilized ascorbate radical which can be recycled back to ascorbate [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, high concentrations of vitamin C showed cellular toxicity on proliferating neural stem/progenitor cells [30]. Furthermore, some lipophilic ASA derivatives with modified hydroxyl groups, as well as conjugates of ASA with pyrimidine, purine, triazole and imidazole bases, exhibited antitumor and antiviral activity [14].…”

Section: Introductionmentioning

confidence: 99%

The Antioxidant and Antiproliferative Activities of 1,2,3-Triazolyl-L-Ascorbic Acid Derivatives

Harej

Macan

Stepanić

et al. 2019

IJMS

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The novel 4-substituted 1,2,3-triazole L-ascorbic acid (L-ASA) conjugates with hydroxyethylene spacer as well as their conformationally restricted 4,5-unsaturated analogues were synthesized as potential antioxidant and antiproliferative agents. An evaluation of the antioxidant activity of novel compounds showed that the majority of the 4,5-unsaturated L-ASA derivatives showed a better antioxidant activity compared to their saturated counterparts. m-Hydroxyphenyl (7j), p-pentylphenyl (7k) and 2-hydroxyethyl (7q) substituted 4,5-unsaturated 1,2,3-triazole L-ASA derivatives exhibited very efficient and rapid (within 5 min) 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging activity (7j, 7k: IC50 = 0.06 mM; 7q: IC50 = 0.07 mM). In vitro scavenging activity data were supported by in silico quantum-chemical modelling. Thermodynamic parameters for hydrogen-atom transfer and electron-transfer radical scavenging pathways of anions deprotonated at C2-OH or C3-OH groups of L-ASA fragments were calculated. The structure activity analysis (SAR) through principal component analysis indicated radical scavenging activity by the participation of OH group with favorable reaction parameters: the C3-OH group of saturated C4-C5(OH) derivatives and the C2-OH group of their unsaturated C4=C5 analogues. The antiproliferative evaluation showed that p-bromophenyl (4e: IC50 = 6.72 μM) and p-pentylphenyl-substituted 1,2,3-triazole L-ASA conjugate (4k: IC50 = 26.91 μM) had a selective cytotoxic effect on breast adenocarcinoma MCF-7 cells. Moreover, compound 4e did not inhibit the growth of foreskin fibroblasts (IC50 > 100 μM). In MCF-7 cells treated with 4e, a significant increase of hydroxylated hypoxia-inducible transcription factor 1 alpha (HIF-1α) expression and decreased expression of nitric oxide synthase 2 (NOS2) were observed, suggesting the involvement of 4e in the HIF-1α signaling pathway for its strong growth-inhibition effect on MCF-7 cells.

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Therapeutic Perspective of Vitamin C and Its Derivatives

Cited by 99 publications

References 131 publications

Molecular Mechanisms of Glucose Fluctuations on Diabetic Complications

Molecular Mechanisms of Glucose Fluctuations on Diabetic Complications

Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone

The Antioxidant and Antiproliferative Activities of 1,2,3-Triazolyl-L-Ascorbic Acid Derivatives

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