Oxidative stress in carcinogenesis: new synthetic compounds with dual effects upon free radicals and cancer.

Tekiner-Gülbaş, Betül; Westwell, Andrew D.; Süzen, Síbel

doi:10.2174/09298673113203690142

Cited by 47 publications

(23 citation statements)

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“…271–279 Under unstressed conditions, Nrf2 remains at a low cellular concentration and is negatively regulated by another cellular component, namely, Kelch-like ECH-associated protein 1 (Keap1). 280 Upon exposure to oxidative stress, Keap1 is deactivated such that Nrf2 escapes from the Keap1-mediated degradation and translocates into the nucleus to transcriptionally activate the ARE-dependent antioxidant genes.…”

Section: Medicinal Aspects Of Chalconesmentioning

confidence: 99%

Chalcone: A Privileged Structure in Medicinal Chemistry

et al. 2017

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Privileged structures have been widely used as an effective template in medicinal chemistry for drug discovery. Chalcone is a common simple scaffold found in many naturally occurring compounds. Many chalcone derivatives have also been prepared due to their convenient synthesis. These natural products and synthetic compounds have shown numerous interesting biological activities with clinical potentials against various diseases. This review aims to highlight the recent evidence of chalcone as a privileged scaffold in medicinal chemistry. Multiple aspects of chalcone will be summarized herein, including the isolation of novel chalcone derivatives, the development of new synthetic methodologies, the evaluation of their biological properties, and the exploration of the mechanisms of action as well as target identification. This review is expected to be a comprehensive, authoritative, and critical review of the chalcone template to the chemistry community.

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Section: Medicinal Aspects Of Chalconesmentioning

confidence: 99%

Chalcone: A Privileged Structure in Medicinal Chemistry

et al. 2017

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“…Oxidative damage (OD) to biological targets such as lipids, proteins, and DNA is a serious health‐threatening phenomenon. It has been held responsible, at least in part, for the onset and development of several diseases including cancer; rheumatoid arthritis; neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, depression, multiple sclerosis, and memory loss; cardiovascular diseases such as atherosclerosis, ischemia, hypertension, cardiac hypertrophy, heart failure, and cardiomyopathy; as well as renal and pulmonary failure . OD arises as a consequence of a chemical imbalance between the production and consumption of oxidants, known as oxidative stress (OS) …”

Section: Introductionmentioning

confidence: 99%

Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

Castañeda‐Arriaga

Pérez-González

Álvarez-Idaboy

et al. 2017

Int J of Quantum Chemistry

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Oxidative damage to biomolecules is a serious health-threatening issue, which leads to the development of several diseases. Oxidative conditions are frequently catalyzed by metal ions. In this study, the role of purines in the copper-catalyzed oxidative stress was investigated using the density functional theory. The obtained results indicate that purines can have a dual behavior, acting as both protectors and promoters of oxidative stress. Their protection role arises from their known radical scavenging activity, as well as their ability to chelate Cu(II) leading to complexes that areto some extent-harder to reduce than free Cu(II). Conversely, their pro-oxidant role is a consequence of their reductant behavior, when deprotonated. Thus, the purines' anions can reduce Cu (II) to Cu(I), making the latter available to be involved in Fenton-like reactions. Consequently, mixtures of purines and Cu(II), at pHs where the fraction of deprotonated purines is rather significant, would yield • OH radicals. In turn, these very reactive radicals would damage biological targets such as lipids, proteins, and DNA.antioxidants, kinetics, pro-oxidants, rate constants, reaction mechanism 1 | I N TR ODU C TI ON Oxidative damage (OD) to biological targets such as lipids, proteins, and DNA is a serious health-threatening phenomenon. It has been held responsible, at least in part, for the onset and development of several diseases including cancer [1][2][3] ; rheumatoid arthritis [4][5][6] ; neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, depression, multiple sclerosis, and memory loss [7][8][9][10][11][12][13] ; cardiovascular diseases such as atherosclerosis, ischemia, hypertension, cardiac hypertrophy, heart failure, and cardiomyopathy [14][15][16][17] ; as well as renal [18][19][20] and pulmonary failure. [21][22][23] OD arises as a consequence of a chemical imbalance between the production and consumption of oxidants, known as oxidative stress (OS). [24] One of the most damaging oxidants in biological systems is the hydroxyl radical ( • OH). It can be produced, in the presence of metal ions such as Fe(II) or Cu(I), by Fenton or Fenton-like reactions (M q 1 H 2 O 2 ! M q11 1OH -1 • OH). However, the most stable and abundant forms of these two metals, under physiological conditions, are Fe(III) and Cu(II). Thus, • OH production would actually involve the metal-catalyzed Haber-Weiss recombination (HWR). It comprises two chemical steps. The first one is the reduction of the metal ions (M q11 1 O •2 2 ! M q 1 3 O 2 ) and the second one is the Fenton reaction. Consequently, redox active metal ions are of particular interest for the chemistry of living systems. These ions cannot only bind to DNA, but they can also promote OD to DNA by mediating the production of oxygen reactive species (ROS). [25] In fact metal-mediated OD to DNA has become an important topic in metal toxicity and carcinogenesis. [26][27][28][29]

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“…This chemical stress has been associated with the onset and development of a wide variety of diseases, such as cancer [1][2][3][4], atherosclerosis [5][6][7][8], Alzheimer's disease [9][10][11][12][13], and cardiovascular disorders [14][15][16][17][18], among many others. OS can be directly triggered by oxidative agents such as reactive oxygen species (ROS), reactive nitrogen species (RNS), and free radicals in general.…”

Section: Introductionmentioning

confidence: 99%

Free-radical scavenging by tryptophan and its metabolites through electron transfer based processes

2015

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Free-radical scavenging by tryptophan and eight of its metabolites through electron transfer was investigated in aqueous solution at physiological pH, using density functional theory and the Marcus theory. A test set of 30 free radicals was employed. Thermochemical and kinetic data on the corresponding reactions are provided here for the first time. Two different pathways were found to be the most important: sequential proton loss electron transfer (SPLET) and sequential double proton loss electron transfer (SdPLET). Based on kinetic analyses, it is predicted that the tryptophan metabolites kynurenic acid and xanthurenic acid are the best free-radical scavengers among the tested compounds; they were estimated to be at least 24 and 12 times more efficient than Trolox for scavenging (•)OOH. These findings are in line with previous reports suggesting that the antioxidant activity that has been attributed to tryptophan is actually due to its metabolites, and they demonstrate the particular importance of phenolic metabolites to such activity. Graphical Abstract Kynurenic acid (KNA) and xanthurenic acid (XNA) are the major contributors to the free-radical scavenging activity of tryptophan.

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Oxidative stress in carcinogenesis: new synthetic compounds with dual effects upon free radicals and cancer.

Cited by 47 publications

References 0 publications

Chalcone: A Privileged Structure in Medicinal Chemistry

Chalcone: A Privileged Structure in Medicinal Chemistry

Role of purines on the copper‐catalyzed oxidative damage in biological systems: Protection versus promotion

Free-radical scavenging by tryptophan and its metabolites through electron transfer based processes

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