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Abstract: Carotenoids are natural pigments attracting attention of physicists, chemists and biologists due to their multiple functions in the nature. While carotenoids have unusually high extinction coefficients, they do not exhibit adequate emission. This fact has resulted in detailed studies of photophysical and photochemical properties of carotenoids and their role as light-harvesting pigments in photosynthesis. Carotenoids are abundantly present in fruits and vegetables and are considered as important species with beneficial effect on human health by decreasing the risk of various diseases, particularly decreasing the incidence of cancers and eye disease. More trials are needed to ascertain the role of carotenoids in prevention of cardiovascular disease and metabolic disease. Carotenoids effectively scavenge peroxyl radicals and act predominantly as antioxidants. However, under conditions of increased concentration of oxygen and carotenoid concentration, beta-carotene was found to exhibit prooxidant behaviour. Photophysical properties of carotenoids and conditions affecting a switch between antioxidant and prooxidant behaviour of carotenoids are the main aims of this review. In addition, the localization of carotenoids in biological membranes, their interactions and reactions with ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) as well as their redox potentials are discussed in view of their antioxidant properties as beneficial species in preventing various diseases. [Copyright &y& Elsevier]

Abstract: Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems. Disruption of metal ion homeostasis may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases, involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer''s disease, Parkinson''s disease), chronic inflammation and others. The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts. On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione. Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed. A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress. It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms. In addition, Zn has an impact on the immune system and possesses neuroprotective properties. The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants. Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), glutathione (GSH), carotenoids, flavonoids, and other antioxidants) are capable of chelating metal ions reducing thus their catalytic acitivity to form ROS. A novel therapeutic approach to supress oxidative stress is based on the development of dual function antioxidants comprising not only chelating, but also scavenging components. Parodoxically, two major antioxidant enzymes, superoxide dismutase (SOD) and catalase contain as an integral part of their active sites metal ions to battle against toxic effects of metal-induced free radicals. The aim of this review is to provide an overview of redox and non-redox metal-induced formation of free radicals and the role of oxidative stress in toxic action of metals. [Copyright &y& Elsevier]

Abstract: Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NOl recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron-transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA. In contrast, beneficial effects of ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain “redox balance” termed also “redox homeostasis”. The “two-faced” character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular “redox homeostasis”; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer''s disease and Parkinson''s disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury. [Copyright &y& Elsevier]

Abstract: The response of the cavity to the movement of a concentrically positioned “over full-length cavity” planar sample of variable length, L=30, 40, and 50mm, and width, , 6, and 8mm, along the vertical, common sample–cavity x-axis in a Bruker single TE102 rectangular cavity (longitudinal effect) has been analysed. The observed dependence of the EPR signal intensity, Ipp, on the sample position, x, showed the following: (i) A plateau, over which the Ipp value remained constant within experimental error of 0.62–2.48%, for sample length of 30 and 40mm. (ii) An “sloping plateau” region, which could be approximated by a linear function (correlation, R=0.83–0.93), for sample length of 50mm. (iii) An additional oscillating component superimposed on the “sloping plateau” region. The trends of these dependencies with the plateau and “sloping plateau” region were independent of the planar sample width, , and its angular position, φ, in the rectangular cavity. But, the EPR signal amplitude on the plateau and “sloping plateau” region obtained for the sample positioned at angles, φ=0° and φ=180° (which corresponded to the experimental configuration, in which the planar sample area is parallel to the waveguide in the microwave cavity) was ca 1.8 times higher compared to those obtained for the sample positioned at angles φ=90° and φ=270° (which corresponded to the experimental configuration, in which the planar sample area is perpendicular to the waveguide). Theoretical predictions of the experimental dependencies of the EPR signal intensity versus sample position along the common sample–cavity x-axis can be calculated using the “sine-squared” function (given by longitudinal integral) modified for an “over full-length cavity” planar sample, and the correlation between observed and theoretically computed dependencies is very good. Each of the above-mentioned phenomenon could be a serious source of significant errors in quantitative EPR spectroscopy. For maximum accuracy in quantitative EPR an “over full-length cavity” planar sample should be compared to a reference sample of identical length which must be identically positioned in the microwave cavity. [Copyright &y& Elsevier]

Abstract: The response of the cavity to the rotation of a concentrically positioned planar sample of variable width, ∈〈1mm,10mm〉, around the common cavity-sample x-axis in a Bruker single TE102 rectangular cavity (radial effect) has been analysed. The observed dependence of the EPR signal intensity, Ipp, on the rotation angle has a general ovaloid shape with an eccentricity, ε, which varies linearly with the width, , of the sample, ε=0.0246+0.0311×, correlation, R=0.996, for samples with a width greater than 2mm but shows a positive deviation from linearity for the 1 and 2mm samples. The dependence of the Ipp value on the planar sample width, , is non-linear for all polar-angle values investigated. These experimental observations are in a very good agreement with theoretical calculations in which the response is modelled using the Cassinian curves modified for planar sample geometry. Similar trends of the angular Ipp dependence were observed for any position of the planar sample as the centre was moved along the vertical x-axis of the cavity. In the longitudinal Ipp dependence for a planar sample whose length, L=30mm, is greater than that of the cavity, then (i) for the case where the whole cavity length is occupied by the sample a constant value for the Ipp (a plateau) is observed and (ii) for sample movement in and out of this plateau region the dependence varies according to the left and right halves of a modified “sine-squared” function. The variation in the signal amplitude along the cavity x-axis (longitudinal effect) can be calculated theoretically using a “sine-squared” curve, modified for an “over full-length cavity” planar sample. In general, the response of the cavity to a planar sample situated at any position on the common sample cavity x-axis can be represented as a product of a modified Cassinian curve and a modified “sine-squared” curve. The non-linear radial effect may give rise to serious sources of systematic error in quantitative EPR spectroscopy with planar sample geometry and shows that accurate and precise positioning of the sample in the microwave cavity is essential. [Copyright &y& Elsevier]

Abstract Copper(II) complexes containing non-steroidal anti-inflammatory drugs (NSAIDs) have been the subject of many research papers and reviews. Here we report the synthesis, spectroscopic study and biological activity of novel mixed copper(II) complexes with NSAIDs: tolfenamic (tolf), mefenamic (mef) and flufenamic (fluf) acids and phenanthroline (phen): [Cu(tolf- O , O′) 2 (phen)] (1), [Cu(mef- O , O ′) 2 (phen)] (2), [Cu(fluf- O , O ′) 2 (phen)] (3). Complexes were characterized by X-ray analysis and EPR spectroscopy. Complexes 1 – 3 are monomeric, six-coordinate and crystallize in a monoclinic space group. Interaction of Cu(II) complexes with DNA was studied by means of absorption titrations, viscosity measurements and gel electrophoresis. The relative ability of the complexes to cleave DNA even in the absence of hydrogen peroxide is in the order 3 > 2 > 1. Application of the reactive oxygen species (ROS) scavengers, L-histidine, DMSO and SOD confirmed that singlet oxygen, hydroxyl radicals (Fenton reaction) and superoxide radical were formed, respectively. Thus, in addition to mechanism of intercalation, redox-cycling mechanism which in turn lead to the formation of ROS contribute to DNA damage. Cu(II) complexes exhibit excellent SOD-mimetic activity in the order 3 ~ 1 > 2. The fluorescence spectroscopy revealed that albumin may act as a targeted drug delivery vehicle for Cu(II) complexes (K ~106). The anticancer activities of complexes 1 – 3 were investigated using an MTS assay (reduction of the tetrazolium compound) against three cancer cell lines (HT-29 human colon adenocarcinoma, HeLa and T-47D breast cancer cells) and mesenchymal stromal cells (MSC). The most promising compound, from the viewpoint of its NSAID biological activity is 3 , due to the presence of the three fluorine atoms participating in the formation of weak hydrogen-bonds at the DNA surface. Graphical abstract Proposed orientation of aryl substituents of the Cu(II) complexes 1 – 3 in their interaction with DNA. The intercalation efficiency of complexes and consequent unwinding of the helix depend on the orientation of remote substituents attached to aromatic rings of the non-steroidal anti-inflammatory drugs (NSAIDs) which can interact with the DNA strand. Unlabelled Image Highlights • Three novel mixed Cu(II) fenamates with phenanthroline were prepared and studied. • Cu(II) complexes are efficient superoxide dismutase-mimetics and DNA intercalators. • Reactive oxygen species-induced DNA damage is a result of a redox-cycling mechanism. • Cu(II) complexes interact with human serum albumin. • Complexes exhibit cytotoxic activity against several cancer cell lines. [ABSTRACT FROM AUTHOR]

Frentizole is immunosuppressive drug with low acute toxicity and lifespan-prolonging effect. Recently, frentizole´s potential to disrupt toxic amyloid β (A β) - A β -binding alcohol dehydrogenase (ABAD) interaction in mitochondria in Alzheimer´s brains has been revealed. Another broadly studied drug with anti-aging and immunosuppressive properties is an mTOR inhibitor – rapamycin. Since we do not yet precisely know what is behind the lifespan-prolonging effect of rapamycin and frentizole, whether it is the ability to inhibit the mTOR signaling pathway, reduction in mitochondrial toxicity, immunosuppressive effect, or a combination of all of them, we have decided within our previous work to dock the entire in-house library of almost 240 A β -ABAD modulators into the FKBP-rapamycin-binding (FRB) domain of mTOR in order to interlink mTOR-centric and mitochondrial free radical-centric theories of aging and thus to increase the chances of success. Based on the results of the docking study, molecular dynamic simulation and MM-PBSA calculations, we have selected nine frentizole-like compounds (1 – 9). Subsequently, we have determined their real physical-chemical properties (logP, logD, pKa and solubility in water and buffer), cytotoxic/cytostatic, mTOR inhibitory, and in vitro anti-senescence (senolytic and senomorphic) effects. Finally, the three best candidates (4 , 8 , and 9) have been forwarded for in vivo safety studies to assess their acute toxicity and pharmacokinetic properties. Based on obtained results, only compound 4 demonstrated the best results within in vitro testing, the ability to cross the blood-brain barrier and the lowest acute toxicity (LD 50 in male mice 559 mg/kg; LD 50 in female mice 575 mg/kg). [Display omitted] • The most studied anti-aging drug is mTOR inhibitor – rapamycin. • Another theory explaining aging is based on excessive free radical production in mitochondria. • Presented compounds (1 – 9) combine both theories (mTOR- and free radical-centric theories). • 1 – 9 showed cytotoxic/cytostatic, mTOR inhibitory, and in vitro anti-senescence effects. • 4 proved to be relatively safe within the test of acute toxicity with the ability to cross the BBB. [ABSTRACT FROM AUTHOR]

Cells produce reactive oxygen species (ROS) as a metabolic by-product. ROS molecules trigger oxidative stress as a feedback response that significantly initiates biological processes such as autophagy, apoptosis, and necrosis. Furthermore, extensive research has revealed that hydrogen peroxide (H 2 O 2) is an important ROS entity and plays a crucial role in several physiological processes, including cell differentiation, cell signalling, and apoptosis. However, excessive production of H 2 O 2 has been shown to disrupt biomolecules and cell organelles, leading to an inflammatory response and contributing to the development of health complications such as collagen deposition, aging, liver fibrosis, sepsis, ulcerative colitis, etc. Extracts of different plant species, phytochemicals, and Lactobacillus sp (probiotic) have been reported for their anti-oxidant potential. In this view, the researchers have gained significant interest in exploring the potential plants spp., their phytochemicals, and the potential of Lactobacillus sp. strains that exhibit anti-oxidant properties and health benefits. Thus, the current review focuses on comprehending the information related to the formation of H 2 O 2, the factors influencing it, and their pathophysiology imposed on human health. Moreover, this review also discussed the anti-oxidant potential and role of different extract of plants, Lactobacillus sp. and their fermented products in curbing H 2 O 2 ‑induced oxidative stress in both in-vitro and in-vivo models via boosting the anti-oxidative activity, inhibiting of important enzyme release and downregulation of cytochrome c, cleaved caspases-3, − 8, and − 9 expression. In particular, this knowledge will assist R&D sections in biopharmaceutical and food industries in developing herbal medicine and probiotics-based or derived food products that can effectively alleviate oxidative stress issues induced by H 2 O 2 generation. [Display omitted] • Oxidative damage-induced H 2 O 2 overexpression leads to inflammation and ROS production. • H 2 O 2 -induced oxidative stress is linked to aging, liver fibrosis, sepsis, ulcerative colitis and cancer. • Plant extracts, phytocompounds, and Lactobacillus sp. and its fermented products have potential to curb oxidative stress. [ABSTRACT FROM AUTHOR]

The radical scavenging and metal chelating properties of flavonoids indicate that they may play a protective role in diseases with perturbed metal homeostasis such as Alzheimer's disease. In this work we investigated the effect of the coordination of quercetin to copper(II) in view of the formation of ROS in Cu-catalyzed Fenton reaction. ABTS and DPPH assays confirmed that the copper(II)-quercetin complex exhibits a stronger radical scavenging activity than does quercetin alone. EPR spin trapping experiments have shown that chelation of quercetin to copper significantly suppressed the formation of hydroxyl radicals in the Cu(II)-Fenton reaction. DNA damage experiments revealed a protective effect for quercetin, but only at higher stoichiometric ratios of quercetin relative to copper. DNA protective effect of quercetin against ROS attack was described by two mechanisms. The first mechanism lies in suppressed formation of ROS due to the decreased catalytic action of copper in the Fenton reaction, as a consequence of its chelation and direct scavenging of ROS by free quercetin. Since the Cu-quercetin complex intercalates into DNA, the second mechanism was attributed to a suppressed intercalating ability of the Cu-quercetin complex due to the mildly intercalating free quercetin into DNA, thus creating a protective wall against stronger intercalators. [ABSTRACT FROM AUTHOR]

The antioxidant properties of flavonoids are mediated by their functional hydroxyl groups, which are capable of both chelating redox active metals such as iron, copper and scavenging free radicals. In this paper, the antioxidant vs. prooxidant and DNA protecting properties of baicalein and Cu(II)-baicalein complexes were studied under the conditions of the Copper-Fenton reaction and of the Copper-Ascorbate system. From the relevant EPR spectra, the interaction of baicalein with Cu(II) ions was confirmed, while UV–vis spectroscopy demonstrated a greater stability over time of Cu(II)-baicalein complexes in DMSO than in methanol and PBS and Phosphate buffers. An ABTS study confirmed a moderate ROS scavenging efficiency, at around 37%, for both free baicalein and Cu(II)-baicalein complexes (in the ratios 1:1 and 1:2). The results from absorption titrations are in agreement with those from viscometric studies and confirmed that the binding mode between DNA and both free baicalein and Cu-baicalein complexes, involves hydrogen bonds and van der Waals interactions. The DNA protective effect of baicalein has been investigated by means of gel electrophoresis under the conditions of the Cu-catalyzed Fenton reaction and of the Cu-Ascorbate system. In both cases, it was found that, at sufficiently high concentrations, baicalein offers some protection to cells from DNA damage caused by ROS (singlet oxygen, hydroxyl radicals and superoxide radical anions). Accordingly, baicalein may be useful as a therapeutic agent in diseases with a disturbed metabolism of redox metals such as copper, for example Alzheimer's disease, Wilson's disease and various cancers. While therapeutically sufficient concentrations of baicalein may protect neuronal cells from Cu-Fenton-induced DNA damage in regard to neurological conditions, conversely, in the case of cancers, low concentrations of baicalein do not inhibit the pro-oxidant effect of copper ions and ascorbate, which can, in turn, deliver an effective damage to DNA in tumour cells. The study of antioxidant vs prooxidant properties of the Copper(II) - baicalein interaction revealed that baicalein may provide protection against Cu-Fenton-induced DNA damage and conversely pro-oxidant effect of copper ions and ascorbate may cause damage to DNA of cancer cell. [Display omitted] • Baicalein and Cu(II)-baicalein complexes were studied. • Binding mode between Cu(II) and baicalein has been Investigated by EPR and UV–vis. • Both systems were studied under the conditions of Cu-Fenton/Cu-Ascorbate systems. • Baicalein offers some protection to cells from DNA damage caused by free radicals. [ABSTRACT FROM AUTHOR]

Cancer and Alzheimer’s disease (AD) are characterized by (i) opposing biological mechanisms, (ii) an inverse correlation between their incidences, and (iii) oxidative stress being a common denominator of both diseases. Increased formation of reactive oxygen species (ROS) in cancer cells from oncogenic signaling and/or metabolic disturbances leads to upregulation of cellular antioxidant capacity to maintain ROS levels below a toxic threshold. Combining drugs that induce high levels of ROS with compounds that suppress cellular antioxidant capacity by depleting antioxidant systems [glutathione (GSH), superoxide dismutase (SOD), and thioredoxin (TRX)] and/or targeting glucose metabolism represents a potential anticancer strategy. In AD, free metals and/or Aβ:metal complexes may cause damage to biomolecules in the brain (via Fenton reaction), including DNA. Metal chelation, based on the application of selective metal chelators or metal delivery, may induce neuroprotective signaling and represents a promising therapeutic strategy. This review examines therapeutic strategies based on the modulation of oxidative stress in cancer and AD. [ABSTRACT FROM AUTHOR]

[Display omitted] • A2 β-casein from milk has some advantageous effects on the gastrointestinal tract. • It is not fully agreed that A1 β-casein has a negative impact on health. • The influence of β-casein variants on milk matrices should be better understood. • UPLC-high-resolution MS and RT-PCR detecting adulteration of A2 milk products. • "Organic A2 milk" represents a strong market trend for the coming years. The genetic variant A2 β-casein integrates the casein protein group in milk and has been often associated with positive health outcomes. Therefore, this review explores the present understanding of A2 β-casein, including detection methods and the market trends for dairy from A2 milk. Also, the interaction of A2 β-casein with αs 1 -casein and κ-casein genotypes was examined in terms of technological impacts on A2 milk. A limited number of preliminary studies has aimed to investigate the sensorial and technological impacts of β-casein variants in milk matrices, for instance, in yogurt and other derivatives. Nevertheless, considering studies carried out so far, it is concluded that the manufacture of dairy products from A2 milk is perfectly feasible, as the products presented slight differences when compared to those derived from traditional milk. In one of the works, sensitive drops in rennet coagulation time and curd firmness values were observed in cheese traits. However, it is relevant to point out that variant A of κ-casein plays a negative role in the coagulation features of milk. Therefore, alterations in the pattern of cheese-making properties are not uniquely related to β-casein variants. Attempts to produce A2 β-casein in laboratory (non-natural source), through biosynthesis, for example, have not been found so far. This knowledge gap offers a promising area for future studies concerning proteins and bioactive peptide production. [ABSTRACT FROM AUTHOR]

Medicinal plants have been exploited for therapeutic purposes since the dawn of civilization and have long been acknowledged essential to human health. The purpose of this research is to examine the scientific evidence for using the therapeutic herbal plants Thalictrum foliolosum DC. and Cordia dichotoma G. Forst. to treat hepatitis illness. The fundamental explanation for the therapeutic relevance of these plants is phytochemicals, which were evaluated qualitatively and quantitatively in three separate extracts with different solvent properties (methanol-polar, chloroform-non-polar, and aqueous-polar as one of the bases of traditional use). Flavonoids, phenols, tannins, saponins, and alkaloids were all evaluated for their presence in plant extracts, and it was observed that methanolic extract had the highest content of phytochemicals among different extracts whereas, the aqueous extract showed least amount of phytochemicals. Additionally, the antioxidant activity of these plants was also evaluated and methanolic extract was revealed with potential antioxidant activity, as also evidenced by the lowest half inhibitory concentration (IC 50) values in the DPPH, ABTS, and high %inhibition in µM Fe equivalent of FRAP assays. Following that, the dominant phytochemicals were investigated using ultra-high performance liquid chromatography from the selected plants. Furthermore, default docking algorithms were used to appraise the dominant phytoconstituents for their in-silico investigation, in which rutin was found with the highest binding affinity (8.2 kcal/mol) and interaction with receptor which is further involved in causing jaundice. The receptor is infact an enzyme that is sphingomyelin phosphodiesterase Leptospira interrogans (PDB: 5EBB) which is holded back in its position by rutin and do not interact with Leptospira inferrogans spp which causes jaundice. Overall, the study suggested that these herbs have significant therapeutic properties, and their in-silico analysis strongly recommends further clinical investigations to get insight into the mechanisms of action in curing variety of diseases. [Display omitted] • Different phytochemicals were derived from the Thalictrum foliolosum and Cordia dichotoma extracts. • Methanolic extracts of T. foliolosum and C. dichotoma exhibited the best antioxidant activity. • In-silico studies confirm the involvement of flavonoids, notably rutin & caffeic acid as antioxidants with jaundice-healing property. • Overall, the phytoconstituents proved to be useful for diseases associated with oxidative stress, primarily jaundice. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a multifactorial disease that is characterized mainly by Amyloid-β (A-β) deposits, cholinergic deficit and extensive metal (copper, iron)-induced oxidative stress. In this work we present details of the synthesis, antioxidant and copper-chelating properties, DNA protection study, cholinergic activity and amyloid-antiaggregation properties of new multifunctional tacrine-7-hydroxycoumarin hybrids. The mode of interaction between copper(II) and hybrids and interestingly, the reduction of Cu(II) to Cu(I) species (for complexes Cu-5e-g) were confirmed by EPR measurements. EPR spin trapping on the model Fenton reaction, using 5,5-dimethyl-1-pyrroline N -oxide (DMPO) as a spin trap, demonstrated a significantly suppressed formation of hydroxyl radicals for the Cu-5e complex in comparison with free copper(II). This suggests that compound 5e upon coordination to free copper ion prevents the Cu(II)-catalyzed decomposition of hydrogen peroxide, which in turn may alleviate oxidative stress-induced damage. Protective activity of hybrids 5c and 5e against DNA damage in a Fenton system (copper catalyzed) was found to be in excellent agreement with the EPR spin trapping study. Compound 5g was the most effective in the inhibition of acetylcholinesterase ( h AChE, IC 50 = 38 nM) and compound 5b was the most potent inhibitor of butyrylcholinesterase ( h BuChE, IC 50 = 63 nM). Compound 5c was the strongest inhibitor of A-β 1–40 aggregation, although a significant inhibition (> 50%) was detected for compounds 5b, 5d, 5e and 5g. Collectively, these results suggest that the design and investigation of multifunctional agents containing along with the acetylcholinesterase inhibitory segment also an antioxidant moiety capable of alleviating metal (copper)-induced oxidative stress, may be of importance in the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Cordia dichotoma , Indian cherry is one of the traditional medicinal plant well-known for its medicinal properties against variety of diseases primarily hepatocellular disorders. C. dichotoma is moderate size tree that may be found throughout the Himachal Pradesh and commonly called as lashuda. The objective of the present study is to emphasize the phytochemical and pharmacological study with hepatocurative assessment of C. dichotoma to strengthen not only traditional knowledge but also to validate scientific value of its medicinal potential. Furthermore, comprehensive literature information of C. dichotoma has been compiled from the variety of sources, including scientific databases like PubMed and Google Scholar and pertinent publications and books. The information provided in this study covers the years from 1956 to 2021 and KingDraw chemical structure editor software was used to depict the chemical structures of various secondary metabolites such as flavonoids, tannins, alkaloids, proteins carbohydrate and phenolic compounds extracted from the different parts of the C. dichotoma. Although, flavonoids and phenolic compounds are the most prominent phytoconstituents predominantly detected in C. dichotoma , which are known for great antioxidant potential and also they are renowned for their various pharmacological and therapeutic efficiency against various chronic diseases. Overall, the studies included in this review implies that the plant and its extracts have significant therapeutic benefits not only for hepatic but also for a variety of diseases. While further research is required to fully understand the processes underlying C. dichotoma application in various pharmacological activities. [Display omitted] • C. dichotoma is one of the ancient medicinal herbs well known for its therapeutic potential against several diseases. • Quercetin is the most significant phytoconstituent responsible for the therapeutic efficacy • Due to its antioxidant effects it has been regarded as a key tool for relieving oxidative stress. • Major phytochemicals like flavonoids and phenols lower down the effect of hepatotoxins. • Flavonoids and phenols have been demonstrated to have various beneficial pharmacological activities. [ABSTRACT FROM AUTHOR]

Refined wool wax products, such as lanoline and lanoline derivatives are key ingredients in some of the ointments, cosmetics, pharmaceuticals, waterproof coatings and other products. Beneficial medicinal effects along with melting point near normal human body temperature designated lanoline to be used in pharmacotherapy and medical treatments. Since the general requirements for sterility of medicinal substances are very strict, especially in cases of skin contact, radiation technologies represent a valuable tool to sterilize the materials for medicinal purposes. In this work, lanoline was irradiated with accelerated electron beam in air within 0–400 kG dose to simulate sterilization for medical purposes. The irradiated lanoline showed considerable fluctuation of chemical structure. The most significant fluctuation was observed for etheric species, followed by ethylene sequences with n <4. While primary and secondary alcohols, as well as epoxides species, decreased below the initial concentration within whole range of the doses, aliphatic esters and ethylene sequences (CH 2 ) n with n ≥4 indicated the most stable species. A trace amount of organic-in origin radicals was observed and that increased slightly with dose. Depending on dose, the melting temperature varied from 39.7 to 45.7 °C and the highest values were reached for 25 kGy and 156 kGy. For these same doses the highest thermal stability was also observed and, simultaneously the thermal stability was related inversely to the destruction rate. We propose, that the chemical transformation of lanoline within 0–25 kGy dose should be tested for prospective medical purposes as well as for the need to eliminate remaining outlasting organic-in-origin radicals which were detected in the lanoline even one year after the irradiation. [ABSTRACT FROM AUTHOR]

Abstract: Polymeric complexes of composition [Cu(3,5-(O2N)2bz)2(μ-denia)1(H2O)1] n (1) (3,5-(O2N)2bz=3,5-dinitrobenzoate) and [Cu(x-O2Nbz)2(μ-denia)1(H2O)1] x =3 (2), x =4 (3) (denia=diethylnicotinamide, and x-O2Nbz=3- or 4-nitrobenzoate) have been prepared, characterized by elemental analysis and studied by electronic, infrared and EPR spectra, as well as by magnetization measurements over the temperature range 1.8–300K, and their structures have been solved. The basic structure unit of all complexes consists of Cu(II) atom monodentately coordinated by the pair of nitrobenzoato anions in trans-positions together with water and diethylnicotinamide molecules, forming nearly tetragonal basal plane of the coordination polyhedron. The axial position of tetragonal–pyramidal coordination polyhedron is occupied by diethylnicotinamide oxygen atom of neighbouring structural unit thus forming spiral polymeric molecule parallel to b-axis. The neighbouring polymeric molecules are stacked by their coordination polyhedron coplanar basal planes and 2D supramolecular layers are formed by supramolecular synthons (10) and (12) including pairs of strong O–H···O hydrogen bonds between coordinated water molecules and uncoordinated carboxylate oxygen atoms. The shortest Cu···Cu interatomic distance of neighbouring copper atoms bridged by those synthons were found 4.606(2)Å for (1), 4.776(2)Å for complex (2) and 4.866(2)Å for (3). Magnetization measurements showed that all complexes (1–3) exhibit maximum of magnetic susceptibility about 6–7K and a fit to Bleaney–Bowers equation gave singlet-triplet energy gap 2J =−6.81cm−1 for (1), 2J =−7.00cm−1 for (2) and 2J =−7.84cm−1 for (3). The results confirm the supramolecular synthons as the paths of antiferromagnetic interactions and magnetically coupled pairs of Cu atoms within the 2D supramolecular layers as an example of difference between the magnetic dimensionality versus the structural dimensionality of all three complexes. [Copyright &y& Elsevier]

Abstract: A new complex of unusual composition [Cu(3-O2Nbz)2(nia)(H2O)2] (1) (nia=nicotinamide, 3-O2Nbz=3-nitrobenzoate) has been prepared and studied together with two other complexes of composition [Cu(4-O2Nbz)2(nia)2(H2O)2] (2) and [Cu(4-O2Nbz)2(nia)2]∙(4-O2NbzH)2 (3) (4-O2Nbz=4-nitrobenzoate). The composition of all complexes has been determined by elemental analysis, the complexes have been studied by electronic, infrared and EPR spectroscopy, as well as by magnetization measurements over the temperature range 1.8–300K, and their structures have been solved. The structure of complex (1) consists of molecules, where Cu(II) atom is monodentately coordinated by the pair of 3-nitrobenzoato anions in trans-positions together with water and nicotinamide molecules, forming nearly tetragonal basal plane, and by another water molecule in axial position of tetragonal-pyramidal coordination polyhedron. The neighboring molecule coordination polyhedron basal planes are coplanar and allow formation of supramolecular dimers with strong H-bonds between hydrogen atoms from equatorially coordinated water molecules and uncoordinated carboxylate oxygen atoms thus giving the nearest CuCu distance of 4.886(2)Å. Magnetization measurements showed that complex (1) exhibits maximum of magnetic susceptibility at 6.5K and a fit to Bleaney-Bowers equation gave singlet–triplet energy gap 2J =−6.25cm−1, and zJ′=−0.03cm−1. This might be an experimental proof that the carboxylate bridges extended with hydrogen bonds are the pathway of the spin–spin interactions. The temperature dependence of changes in EPR spectra of (1) and the spectrum at 4.2K have confirmed its hydrogen bonded dimeric structure. The calculated CuCu distance 4.8Å is in very good agreement with the value obtained from crystal structure. The complexes (2) and (3) at 300K exhibit magnetic moment μ eff =1.98B.M. and μ eff =1.84B.M., respectively. These values practically do not change with lowering the temperature up to 5K and only small drops to μ eff =1.87B.M. (for (2)) and μ eff =1.79B.M. (for (3)) at 1.8K have been observed. The EPR spectra of complex (2) at room temperature as well as at 77K are of axial type with g⊥ = 2.062 and g || =2.285 and exhibit resolved parallel hyperfine splitting with A || =160Gauss. The EPR spectra of complex (3) at room temperature as well as at 77K are of axial type with g⊥ =2.065 and g || =2.235 and exhibit unresolved parallel hyperfine splitting. EPR spectra of (2) and (3) are consistent with the X-ray structure. [Copyright &y& Elsevier]

Luteolin has been reviewed as a flavonoid possessing potential cardioprotective, anti-inflammatory, anti-cancer activities. Having multiple biological effects, luteolin may act as either an antioxidant or a pro-oxidant. In this work, the protective role of copper(II)-chelation by luteolin on DNA damage via the Cu-Fenton reaction was studied. EPR and UV–vis spectroscopic data demonstrated that the luteolin, lacking 3-OH group, chelates to Cu(II) via the 5-OH and 4-CO groups, respectively. EPR spin trapping experiments using DMPO spin trap confirmed that the coordination of luteolin to Cu(II) significantly suppressed formation of hydroxyl and superoxide radicals (by 80%) in a Cu-Fenton system. Absorption titrations showed that the chelation of Cu(II) by luteolin slightly increased the mild intercalation strength of its interaction with DNA, as compared with free luteolin. Comparison with kaempferol and quercetin revealed, that the strength of the interaction between the free flavonoids/Cu-flavonoid complexes with DNA is only mildly affected by the presence/absence of 3-OH group. Due to the differences in the sensitivities of absorption titrations and viscometry, the latter confirmed weaker DNA intercalating efficiency of Cu-luteolin complex than does free luteolin. A dose dependent protective effect of luteolin against ROS-induced DNA damage was observed using gel electrophoresis. This effect was more pronounced compared to quercetin and kaempferol. In conclusion, the administration of luteolin to patients suffering from oxidative stress-related diseases with disturbed Cu-metabolism such as Alzheimer's diseases (antioxidant effect) and certain cancers (prooxidant effect) may have several health benefits. [Display omitted] • Antioxidant/prooxidant properties of luteolin in a Cu-Fenton reaction were studied. • EPR spin trapping experiments confirmed suppressed formation of hydroxyl radicals. • Interaction of Cu-luteolin complex with DNA was studied by absorption titrations. • DNA damage was studied by gel electrophoresis. [ABSTRACT FROM AUTHOR]