Lead (Pb), a ubiquitous and potent neurotoxicant, induces several neurophysiological and behavioural changes, while Pb alters the function of multiple organs and systems, it primarily affects the central nervous system. In human adults, encephalopathy resulting from Pb intoxication is often characterized by sleeplessness, poor attention span, vomiting, convulsions and coma; ...

Alnumycin A is an aromatic polyketide with a strong resemblance to related benzoisochromanequinone (BIQ) antibiotics such as the model antibiotic actinorhodin. One intriguing difference between these metabolites is that the positions of the benzene and quinone rings are reversed in alnumycin A in comparison to the BIQ polyketides. In this ...

The catalytic asymmetric synthesis of tertiary alcohols by the addition of organometallic reagents to ketones is of central importance in organic chemistry. The resulting quaternary stereocentres are difficult to prepare selectively by other means despite their widespread occurrence in natural products and pharmaceuticals. Here we report on a new methodology ...

The cervical spinal cords of 2 horses with equine degenerative myeloencephalopathy (EDM) were evaluated for evidence of oxidative damage to the central nervous system (CNS) using immunohistochemical staining for 3-nitrotyrosine (3-NT) and 4-hydroxynonenol (4-HNE). Neurons of the CNS from horses with EDM had positive immunohistochemical staining, whereas control samples did ...

The title compound, C(20)H(14)Cl(4)O, was prepared by the reaction of 2,6-dichloro-benzaldehyde and cyclo-hexa-none. In the mol-ecule, the central cyclo-hexa-none ring adopts an envelope conformation, while the terminal benzene rings make a dihedral angle of 57.87 (9)°.

The digestive stability of two natural antioxidant compounds present in virgin olive oil, hydroxytyrosol (HTy) and hydroxytyrosyl acetate (HTy-Ac) and a new series of hydroxytyrosyl ethers (methyl, ethyl and butyl hydroxytyrosyl ethers) was evaluated by a simulated digestion procedure. High recovery of all compounds after gastric digestion was obtained, although ...

The macrocyclic diarylether heptanoid (MDEH) natural products have been used in folk medicine for centuries. MDEHs are reported to exert anti-tumor properties by inhibiting the activation of NF-κB. Here we report the synthesis of a small MDEH library (first reported synthesis of racemic platycarynol) using a Grubbs cross metathesis/Ullmann cyclization ...

Significance: Chronic Pancreatitis is a progressive, inflammatory disease of the pancreas leading to slow destruction of pancreatic parenchyma and progressive fibrosis. The pathophysiological mechanism of chronic pancreatitis is not well understood. Recent Advances: A pathophysiologic role of oxidative stress in chronic pancreatitis has however, been suggested in recent years. Pancreatic ...

The in vitro reactivity of capsanthin (1) and fuocoxanthin (2) with peroxynitrite was investigated, and the reaction products produced by scavenging with peroxynitrite were analyzed. (14'Z)-Nitrocapsanthin (3) and 12-nitrocapsanthin (4) were isolated from the products of the reaction of capsanthin with peroxynitrite. Similarly, (14Z)-15-nitrofucoxanthin (5), (11Z)-11-nitrofucoxanthin (6), and (14Z,9'Z)-15-nitrofucoxanthin (7) ...

Here we describe the design and synthesis of two series of 4-pyrrylamino quinazolines as new analogues of the EGFR inhibitor Gefitinib. In vitro antitumor activity of these novel compounds against pancreatic (Miapaca2) and prostate (DU145) cancer cell lines was evaluated. Compared with the parental Gefitinib, all the 18 derivatives show ...

Synthesis, SAR and physico-chemical properties of an alkyl aminothiazole series 8 and 16 are described. 2-Pyridylaminothiazole based compounds such as 8c and 16a exhibit high affinity at the NPY(5) receptor with desirable cLogPs and solubilities. However, they also suffer from high in vitro and in vivo clearance. Compound 16a partially ...

Abstract Significance: Nitric oxide (NO), a ubiquitous gaseous signaling molecule, contributes to both pancreatic physiology and pathophysiology. Recent Advances: The present review provides a general overview of NO synthesis, signaling, and function. Further, it specifically discusses NO metabolism and its effects in the exocrine pancreas and focuses on the role ...

BACKGROUND: Oxidative stress-induced free radicals have been implicated in the pathology of chronic pancreatitis (CP). AIM: We aimed to estimate oxidative stress and antioxidant status in tropical chronic pancreatitis (TCP) and alcoholic chronic pancreatitis (ACP) and correlate with zinc status. METHODS: One hundred and seventy-five CP patients (91 TCP, 84 ...

Electrochemistry and electrocatalysis on carbon nanomaterials is at the forefront of research. The presence of carbonaceous and metallic impurities within carbon nanotubes (CNTs) is a persistent problem. Here we show that the electrochemistry of the entire group of hydrazine compounds is governed by impurities within single-walled, double-walled and few-walled CNTs. ...

Sequential aldol condensation of aldehydes with methyl ketones followed by transition metal-catalyzed addition reactions of arylboronic acids to form β-substituted ketones is described. By using the 1,1'-spirobiindane-7,7'-diol (SPINOL)-based phosphite, an asymmetric version of this type of sequential reaction, with up to 92% ee, was also realized. Our study provided an ...

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 ...

2-Alkenylbenzylidene hydrazones 5a-m, which are accessible in good to excellent yields in a four-step synthesis, are converted into 1,2-diaza-4,5-benzoheptatrienyl metal compounds 1a-m by treatment with KO-t-Bu as base. These metal compounds undergo the various types of reactions in good yields and exclusively depending on the nature of substituents R(1) and ...

Only a handful of aziridine-containing natural products have been identified out of the more than 100,000 natural products characterized to date. Among this class of compounds, only the azinomycins (azinomycin A and B) and ficellomycin contain an unusual 1-azabicyclo[3.1.0]hexane ring system, which has been reported to be the reason for ...

A fast, high-yielding synthesis of diaryl ethers with use of mild and metal-free conditions has been developed. The scope includes bulky ortho-substituted diaryl ethers, which are difficult to obtain by metal-catalyzed protocols. Halo-substituents, racemization-prone amino acid derivatives, and heteroaromatics are also tolerated. The methodology is expected to be of high ...

This review surveys the chemical, biological, and mycological literature dealing with the isolation, structural elucidation, biological activities, and synthesis of nitrogen-containing compounds from the fruiting bodies or the culture broths of macromycetes.

Toxic effects of selected metallic oxides nanoparticles were studied using the short-term static bioassays. Nanoparticles were more toxic than comparable bulk metallic oxides. Freshwater sludge worm Tubifex tubifex can be used as suitable test model for nanoecotoxicological studies in future studies.

While C-H oxidation by ruthenium oxo compounds has been broadly applied in organic synthesis, examples of C-H oxidation by metal oxo complexes from the rest of the platinum group are still rare. We survey the preparation and reactivity of these late-transition metal oxo and peroxo complexes in this tutorial review.

The protective effect of KIOM-4, a mixture of plant extracts, was examined against streptozotocin (STZ)-induced mitochondrial oxidative stress in rat pancreatic β-cells (RINm5F). KIOM-4 scavenged superoxide and hydroxyl radicals generated by xanthine/xanthine oxidase and Fenton reaction (FeSO(4)/H(2)O(2)), respectively, in a cell-free chemical system. In addition, a marked increase in mitochondrial ...

Hyperhomocysteinemia was first associated with degenerative disease by observation of accelerated arteriosclerosis in children with inherited disorders of cystathionine synthase, methionine synthase, and methylene tetrohydrofolate reductase. The metabolic blockade of sulfate synthesis from homocysteine thiolactone in malignant cells is ascribed to a deficiency of a chemopreventive derivative of homocysteine thiolactone ...

Naturally-occurring nitro compounds display great structural diversity, and a wide range of biological activities. This review summarizes current information on the structures of naturally-occurring nitro compounds and on the biosynthesis of the nitro group.

A complete reversal of diastereoselectivity was observed for reactions of the trifluoroacetaldehyde ethyl hemiacetal with enamines and imines, derived from propiophenones, that produce 4,4,4-trifluoro-1-aryl-3-hydroxy-2-methyl-1-butanones. This process serves as the first reliable, metal-free, complementary anti- and syn-selective method to prepare 4,4,4-trifluoro-1-aryl-3-hydroxy-2-methyl-1-butanones.

This paper describes a versatile, and simple synthetic route for the preparation of a range of reduced graphene oxide (RGO)-metal/metal oxide composites and their application in water purification. The inherent reduction ability of RGO has been utilized to produce the composite structure from the respective precursor ions. Various spectroscopic and ...

Minocycline prevents oxidative protein modifications and damage in disease models associated with inflammatory glial activation and oxidative stress. Although the drug has been assumed to act by preventing the up-regulation of proinflammatory enzymes, we probed here its direct chemical interaction with reactive oxygen species. The antibiotic did not react with ...

A novel fluorescent probe, HKGreen-3, for sensing peroxynitrite is designed on the basis of the rhodol scaffold and a peroxynitrite-specific oxidation reaction. The probe turns out to be highly sensitive and selective for detecting peroxynitrite in both chemical and biological systems.

Abstract The peroxynitrite-induced functional impairment of myosin was studied in different reaction conditions, known to alter the oxidative chemistry of peroxynitrite, to better understand the molecular mechanisms of this interaction. It is shown that peroxynitrite is able to enhance the basal MgATPase activity up to 2-fold while inhibiting the actin-stimulated ...

Impairment of the mitochondrial electron transport chain has been suggested to be a critical factor in the neuropathogenesis of Parkinson's disease (PD), as inhibition of mitochondrial complex I (CI) activity is consistently detected in PD patients as well as in mitochondrial toxin models of the disorder. Increased levels of various ...

Nitric oxide synthases (NOSs) are multi-domain hemothiolate proteins that are the sole source of nitric oxide (NO) in mammals. NOSs can also be a source or a sink for peroxynitrite (PN), an oxidant that is suspected to be involved in numerous physiopathological processes. In a previous study, we showed that ...

Nitric oxide synthases (NOSs) are multi-domain hemothiolate proteins that are the sole source of nitric oxide (NO) in mammals. NOSs can also be a source or a sink for peroxynitrite (PN), an oxidant that is suspected to be involved in numerous physiopathological processes. In a previous study, we showed that ...

Peroxynitrite is a reactive oxidant produced from nitric oxide and superoxide, which reacts with proteins, lipids, and DNA, and promotes cytotoxic and proinflammatory responses. Here, we overview the role of peroxynitrite in various forms of circulatory shock. Immunohistochemical and biochemical evidences demonstrate the production of peroxynitrite in various experimental models ...

The focus of this Forum Article highlights work from our own laboratories and those of others in the area of biochemical and biologically inspired inorganic chemistry dealing with nitric oxide [nitrogen monoxide, *NO((g))] and its biological roles and reactions. The latter focus is on (i) oxidation of *NO((g)) to nitrate ...

Cellular damage occurring under oxidative conditions has been ascribed mainly to the formation of peroxynitrite (ONOOH/ONOO(-)) that originates from the reaction of NO(*) with O(2) (*-). The detrimental effects of peroxynitrite are exacerbated by the reaction with CO(2) that leads to ONOOC(O)O(-), which further decays to the strong oxidant radicals ...

Oxidant damage from reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major contributor to the cellular damage seen in numerous types of renal injury. Resveratrol (trans-3,4',5-trihydroxystilbene) is a phytoalexin found naturally in many common food sources. The anti-oxidant properties of resveratrol are of particular interest because of ...

The coexistence of nitric oxide and superoxide leads to complex oxidative and nitrosative chemistry, which has been implicated in many pathophysiological conditions. The present study investigated the role of ascorbate in affecting the kinetics of nitrosative chemistry in a model dynamic snystem of coexisting nitric oxide and superoxide. SIN-1 (3-morpholinosydnonimine) ...

Pathogenic bacteria elicit protective responses to oxidative and nitrosative stresses. Although such responses are generally distinct, it was recently reported in Mycobacterium tuberculosis that catalase-peroxidase (KatG), a classical defence against peroxides, also exhibits peroxynitritase activity. Here, the katG gene from Salmonella Typhimurium was cloned and protein purified and characterised. An ...

NO dioxygenation, i.e., the oxidation of nitric oxide to nitrate by oxygen-bound truncated hemoglobin (trHbN) is studied using reactive molecular dynamics simulations. This reaction is an important step in a sequence of events in the overall NO detoxification reaction involving trHbN. The simulations ( approximately 160 ns in total) reveal ...

There is much interest in the nitration and oxidation reaction mechanisms initiated by superoxide radical anion (O(2)()) and nitric oxide ((*)NO). It is well known that O(2) and (*)NO rapidly react to form a potent oxidant, peroxynitrite anion (ONOO(-)). However, indirect measurements with the existing probes (e.g. dihydrorhodamine) previously revealed ...

Cellular mechanisms of CO2 chemoreception are discussed and debated in terms of the stimuli produced during hypercapnic acidosis and their molecular targets: protons generated by the hydration of CO2 and dissociation of carbonic acid, which target membrane-bound proteins and lipids in brain stem neurons. The CO2 hydration reaction, however, is ...

The kinetics of the reaction of lactoperoxidase with peroxynitrite was studied under neutral and acidic pH. Lactoperoxidase catalyses peroxynitrite decay with the rate constant, k(c), increasing with decreasing pH. The values of k(c) obtained at pH 7.1, 6.1 and 5.1 are (1.9+/-0.1)x10(6), (5.0+/-0.1)x10(6) and (8.5+/-0.2)x10(6) M(-1)s(-1), respectively. This tendency means ...

In this paper, the effect of some commonly used antithyroid drugs and their analogues on peroxynitrite-mediated nitration of proteins is described. The nitration of tyrosine residues in bovine serum albumin (BSA) and cytochrome c was studied by Western blot analysis. These studies reveal that the antithyroid drugs methimazole (MMI), 6-n-propyl-2-thiouracil ...

In the present study it was shown that resveratrol (3,4,5-trihydroxystilbene), an efficient light-absorbing molecule, during its transition from trans to cis configuration under UV light, transfers its energy of excitation to triplet oxygen to produce singlet oxygen ((1)O(2)). This transition is prevented by Trolox, a quencher of singlet oxygen. In ...

This work evaluates the protective effects of Chinese herbs against ONOO(-)-induced biomolecule damage. Thirty-two Chinese traditional herbs were preliminarily screened for their ONOO(-)-scavenging activity by the fluorometric method. The potency of scavenging activity was in the following order: Apis cerana Fabricius (Propolis) > Rosmarinus officinalis L (Rosemary) > Pseudolarix amabilis ...

AIMS: Preeclampsia is a hypertensive disorder characterized by vascular oxidative stress. Decreased availability of the vasodilator nitric oxide (NO) has been postulated to be involved in the pathophysiology of this disorder. Arginase, an enzyme that competes with nitric oxide synthase (NOS) for l-arginine, not only reduces NO formation but also ...

Approximately 15 years ago we reported that cytochrome c oxidase (CcO) was persistently inhibited as a consequence of endogenous induction and activation of nitric oxide ((*)NO) synthase-2 (NOS2) in astrocytes. Furthermore, the reactive nitrogen species implicated was peroxynitrite. In contrast to the reversible inhibition by (*)NO, which occurs rapidly, in ...

Inducible NOS (iNOS) is induced in diseases associated with inflammation and oxidative stress, and questions remain regarding its regulation. We demonstrate that reactive oxygen/nitrogen species (ROS/RNS) dose-dependently regulate iNOS function. Tetrahydrobiopterin (BH4)-replete iNOS was exposed to increasing concentrations of ROS/RNS and activity was measured with and without subsequent BH4 addition. ...

Peroxynitrite and hypochlorite are oxidants relevant in many pathological situations. We propose a simple spectrofluorometric assay to determine antioxidant capacity against hypochlorite and peroxynitrite based on protection against fluorescein bleaching. The assay can be performed on a microplate and requires minute amounts of material. Standard antioxidants show different reactivities for ...