Development Of New Antioxidants Research Articles

Synthesis of novel vicinal diaryl triazoles with sulfur and hydrazine linkers as highly potent anticancer and antioxidant agents

Heading the list of the critical health-related issues worldwide, cancer continues to be one of the most serious life-threatening diseases. Moreover, development of new antioxidants is a field of growing interest because some synthetic antioxidants such as BHA and BHT are now suspected to be potentially harmful to human health. Accordingly, two series of 1,2,4-triazole–ring-containing combretastatin analogs; 8a-j with sulfur linker and 9a-j with hydrazine linker were synthesized. All twenty compounds were tested in vitro for their anticancer activity on three different cancer cell lines including A549, MCF7, and HepG2. A superior cytotoxic activity of all compounds with sulfur linker (8) as compared to doxorubicin, on A549, MCF7 cancer cells, was observed. Furthermore, the best results against HepG2 were obtained for 8e, 8c, 8f and 8g. In addition, compound 8g has also exhibited strong binding affinity against estrogen receptor alpha through in silico molecular docking simulations. Moreover, the antioxidant activity of all derivatives was evaluated using FRAP assay and DPPH test. The compounds 8e, bearing 3,4,5‑methoxy phenyl moiety, and 9g, carrying fluorophenyl group, were the most potent radical scavengers in the DPPH method and also had the superior capacity in the FRAP assay.

Advances in Research on the Activity Evaluation, Mechanism and Structure-Activity Relationships of Natural Antioxidant Peptides.

Antioxidant peptides are a class of biologically active peptides with low molecular weights and stable antioxidant properties that are isolated from proteins. In this review, the progress in research on the activity evaluation, action mechanism, and structure-activity relationships of natural antioxidant peptides are summarized. The methods used to evaluate antioxidant activity are mainly classified into three categories: in vitro chemical, in vitro cellular, and in vivo animal methods. Also, the biological effects produced by these three methods are listed: the scavenging of free radicals, chelation of metal ions, inhibition of lipid peroxidation, inhibition of oxidative enzyme activities, and activation of antioxidant enzymes and non-enzymatic systems. The antioxidant effects of natural peptides primarily consist of the regulation of redox signaling pathways, which includes activation of the Nrf2 pathway and the inhibition of the NF-κB pathway. The structure-activity relationships of the antioxidant peptides are investigated, including the effects of peptide molecular weight, amino acid composition and sequence, and secondary structure on antioxidant activity. In addition, four computer-assisted methods (molecular docking, molecular dynamics simulation, quantum chemical calculations, and the determination of quantitative structure-activity relationships) for analyzing the structure-activity effects of natural peptides are summarized. Thus, this review lays a theoretical foundation for the development of new antioxidants, nutraceuticals, and cosmetics.

The extraction, structural characterization and bioactivity of LCC from eucalyptus chips and its Pre-hydrolysis solution

In order to explore the potential differences in the structural characterisation of the LCC, LCC-AcOH and lignin fractions in eucalyptus chips and eucalyptus pre-hydrolysates, and the different biological activities caused by the different structural characterisation, we extracted and purified LCC, LCC-AcOH and lignin fractions from the two raw materials respectively. The structural analysis of the LCC, LCC-AcOH and lignin fractions was carried out with HPAEC, GPC, FT-IR, TGA, 2D HSQC NMR, and other tests. It then studied the scavenging rate of DPPH and hydroxyl radicals by these fractions, and the inhibition effect on S.aureus, E.coli and Bacillus subtilis, generally exploring the relationship between their antioxidant properties, inhibition properties and structure. The results showed this: the main linkages in eucalyptus LCC were PhGlc and γ-Est, and that hot water pretreatment caused the γ-Est in LCC to break and fail to recombine. The LCC extracted from the pre-hydrolysate contained only S-type lignin structural units and were linked by β-O-4' linkages, whereas the lignin of the other five fractions was GS-type lignin and the main linkages were β-O-4', β-β' and β-5' linkages. In addition, both EPHL-LCC-AcOH and EC-LCC-AcOH had better hydrophilic and biocompatible properties since they contained more acid-soluble lignin and carbohydrates, and both had good antioxidant and antibacterial properties respectively, which made them more potential for the development of new antioxidants and antibacterial agents.

Central nervous system injury meets nanoceria: opportunities and challenges.

Central nervous system (CNS) injury, induced by ischemic/hemorrhagic or traumatic damage, is one of the most common causes of death and long-term disability worldwide. Reactive oxygen and nitrogen species (RONS) resulting in oxidative/nitrosative stress play a critical role in the pathological cascade of molecular events after CNS injury. Therefore, by targeting RONS, antioxidant therapies have been intensively explored in previous studies. However, traditional antioxidants have achieved limited success thus far, and the development of new antioxidants to achieve highly effective RONS modulation in CNS injury still remains a great challenge. With the rapid development of nanotechnology, novel nanomaterials provided promising opportunities to address this challenge. Within these, nanoceria has gained much attention due to its regenerative and excellent RONS elimination capability. To promote its practical application, it is important to know what has been done and what has yet to be done. This review aims to present the opportunities and challenges of nanoceria in treating CNS injury. The physicochemical properties of nanoceria and its interaction with RONS are described. The applications of nanoceria for stroke and neurotrauma treatment are summarized. The possible directions for future application of nanoceria in CNS injury treatment are proposed.

New bioactive peptides from the venom gland of a social hornet Vespa velutina

Bacterial resistance to drugs is a global problem requiring the urgent development of new antibiotics. Antimicrobial peptides (AMPs) are excellent candidates for the design of novel antibiotics to combat microbial resistance. In this research, we identified four new peptides (U-VVTX-Vp1a, U-VVTX-Vp1b, U-VVTX-Vp2a, and U-VVTX-Vp2b, respectively) from the venom of Vespa velutina, and tested their antimicrobial, antioxidant, and hemolytic effects. All four peptides showed scavenging ability against DPPH, ABTS+, and •OH free radicals. Of note, Vp1b strongly inhibited the growth of Staphylococcus aureus and Escherichia coli bacteria at concentrations of 60 and 120 μM. Due to their low hemolytic activity, all four peptides could be utilized in the development of new antioxidants and as candidates for the design of novel antimicrobial agents.

Molecular design of curcumin analogues with potent antioxidant properties and thermodynamic evaluation of their mechanism of free radical scavenge

BackgroundFree radical attack of cellular structures in the human system is the major cause of various forms of degenerative diseases. Consequently, recent research has been focused on the development of new antioxidants with more efficient free radical scavenging potentials. Ligand-based virtual screening was employed in the rational design of potent antioxidant derivatives of curcumin by the density functional theory method. Various antioxidant descriptors that characterize the three major mechanisms of free radical scavenge, namely, hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET), were calculated. Also, the spin density distribution on the generated radicals and the frontier orbital distribution and energy of the studied compounds were evaluated in order to gain further insight on the reaction mechanism. The reaction Gibbs free energy for scavenging the two important peroxyl radicals (HOO· and CH3OO·) was calculated in order to evaluate the preferred mechanism of free radical scavenge by these compounds.ResultsThe investigated compounds were able to scavenge HOO· and CH3OO· radicals by HAT and SPLET mechanisms in the gas phase and aqueous solution, based on the computed results of reaction enthalpies and Gibbs free energy. The SET-PT mechanism for these compounds was observed to be thermodynamically unfeasible in the gas phase. However, the thermodynamic feasibility of free radical scavenge by SET-PT mechanism was observed in aqueous solution. Among the investigated compounds, MCC 009 (1E,4E)-1-(3-(aminomethyl)-4-hydroxyphenyl)-5-(4-hydroxy-3-((hydroxy (methyl)amino)methyl)phenyl)penta-1,4-dien-3-one at the 19-OH position possessed the highest capacity to scavenge both HOO· and CH3OO· radicals by HAT, SET-PT, and SPLET mechanisms. The reaction Gibbs free energy of scavenging HOO· radical by this molecule in the gas phase and aqueous solution is ∆rGBDEgas = − 58.18, {Delta _r{G}_{BDE}}_{H_2O}=-73.77 , ∆rGAIPgas = 611.48, {Delta _r{G}_{AIP}}_{H_2O}=-74305.49 , ∆rGPDEgas = − 669.66, {Delta _r{G}_{PDE}}_{H_2O}=74231.72 , ∆rGPAgas = − 271.40, {Delta _r{G}_{PA}}_{H_2O}=-73.09 ,∆rGETEgas = 213.22, and {Delta _r{G}_{ETE}}_{H_2O}=-0.69 .ConclusionNew set of curcumin derivatives with potent free radical scavenging properties was successfully designed, and their mechanism of free radical scavenging evaluated by thermodynamic studies. This research is a gateway to the exploitation of the considered curcumin derivatives in food chemistry and pharmacy.

Investigations of antiproliferative and antioxidant activity of β-lactam morpholino-1,3,5-triazine hybrids

This article reports for the first time the synthesis of some novel β-lactam morpholino-1,3,5-triazine hybrids by a [2+2]-cycloaddition reaction of imines 7a–c, 9a–c and 11 with ketenes derived from substituted acetic acids. The reaction was totally diastereoselective, leading exclusively to the formation of cis-β-lactams 8a–l, 10a–f and 12a–c. The synthesized compounds were tested for activity towards SW1116, MCF-7 and HepG2 cancer cell lines and non-cancerous HEK-293 cell line by MTT assay. None of the compounds exert an observable effect on HepG2, MCF-7 and HEK-293 cells, but compounds 7b, 8f, 8g, 8l, 10c, and 10e exhibited excellent growth inhibitory activity (IC50 < 5 µM) against SW 1116 cells, comparable to that of doxorubicin (IC50 = 6.9 µM). An evaluation of the antioxidant potential of each of the compounds, performed by diphenylpicrylhydrazyl (DPPH) assay, indicated that 7b, 9a, 9b and 9c have strong free radical scavenging activity. UV absorption titration studies reveal that 7b, 8l, 8g and 8f interact strongly with calf-thymus DNA (CT-DNA) in the order of 8l > 7b > 8f > 8g. Collectively, the in vitro capabilities of some of these morpholino-triazine imines and β-lactams suggest possible applications to development of new antioxidants and DNA binding therapeutics.

Combining electronic properties and virtual screening for the development of new antioxidants: Trolox‐like compounds as application example

AbstractOxidative stress is an imbalance between the production of free radicals and the antioxidant defenses of the organism. Heart diseases, anemia, inflammation, and neurodegenerative disorders have been associated with this biological condition. Trolox is a notable antioxidant drug similar to vitamin E, and it is used to decrease the oxidative stress or repair the damage caused by it. In this work, the virtual screening technique is applied to identify compounds with antioxidant activities similar to Trolox. The antioxidant activity of these compounds was assessments by the mechanisms of hydrogen atom transfer and single electron transfer. Properties such as bond dissociation enthalpy, adiabatic ionization potential, Gibbs free reaction energy, spin density, highest occupied molecular orbital (HOMO), and GAP (HOMO‐LUMO) energies, obtained from the DFT approach, point out to the predominance of the HAT mechanism for the antioxidant action of these compounds. The obtained results contribute to a better understanding of the chemical and physical properties responsible for antioxidant activity and the design of new antioxidant agents.

Optimizing oxygen functional groups in graphene quantum dots for improved antioxidant mechanism.

The development of new antioxidants with quick absorbance of free radicals and excellent biocompatibility has drawn intensive attention in recent years. Graphene quantum dots (GQDs) seemed to be one of the most promising antioxidants because of their appropriate antioxidant activity, unique structure, excellent biocompatibility, and low toxicity. However, the relatively low antioxidant activity in comparison with inorganic semiconductor materials and unclear antioxidant mechanism limited their application in cells. In this paper, we further explored their antioxidant mechanism by focusing on the relationship between antioxidant activity and surface oxygen functional groups. The total oxygen fraction was controlled by post-preparation reduction using NaBH4 and the type of oxygen functional groups was adjusted by free radicals during the preparation of GQDs. The degree of reduction and content of surface oxygen groups were determined by X-ray photoelectron spectroscopy (XPS), and the antioxidant activity was obtained by scavenging of 1,1-diphenyl-2-picryl-hydrazyl (DPPH˙) and hydroxyl (˙OH) free radicals. Based on the analysis of XPS, Raman, and Fourier-transform infrared (FT-IR) spectra, the relationship between antioxidant activity and the surface oxygen groups of GQDs was obtained, and the antioxidant mechanism of GQDs was revealed with a particular specification of each oxygen group in the antioxidant activity of GQDs, meanwhile, the biocompatibility of GQDs has been demonstrated by cytotoxicity tests. We hope that our results will provide a new insight into a complete antioxidant mechanism of GQDs.

In-vitro antioxidants, antimicrobial and toxicological evaluation of Nigerian Zingiber officinale

BackgroundZingiber officinale is a rhizome commonly consumed as a delicacy, medicine or spice. It is considered as a safe spice with several medicinal properties. The aim of this study was to evaluate in-vitro antioxidants, antimicrobial and safety of Nigerian Z. Officinale.MethodsMethanol extract of Nigerian Z. Officinale (MEZO) was evaluated for phytochemical composition, total flavonoids and phenol contents using standard procedures. Antibacterial study was carried out via the agar well diffusion method. Antioxidant activities were carried out using 2, 2′- diphenyl-1- picrylhydrazyl (DPPH), and ferric reducing antioxidant properties (FRAP) assay. Twenty five (25) wister rats were randomly grouped into five (A-E) of five animals each. Animals in Groups A-D were orally administered 75,150, 300 and 600 mg/kg bwt of the extract on daily basis for 4 weeks while those in Group A (control) received distilled water.ResultsTotal phenolic and flavonoids contents of the extract were 15.24 ± 0.02 mg GAE/g and 19.84 ± 0.32 mg/g CE respectively. The extract promoted an inhibition of free radicals with IC50 values of 47.05 ± 2.03 μg/mL and 89.15 ± 0.29 μg/mL in DPPH and FRAP assay. At extract concentration of 100 μg/mL, K. pneumoniae showed the highest susceptibility of 29.04 ± 0.35 mm, followed by P. aeuruginisa (26.03 ± 0.41 mm), while S. aureus (15.08 ± 0.20 mm) was least susceptible. The serum concentrations of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), sodium, albumin, total proteins and the computed organs/body weight ratios compared favorably (p > 0.05) with control at all extract doses tested. The bilirubin, urea and creatinine levels significantly (p < 0.05) increase while chloride decreases in rats dosed 600 mg/kg bwt. However, potassium level increases significantly (p < 0.05) in rats dose 300 mg/kg of the extract when compare with the control.ConclusionThis study revealed the strong antioxidant and antimicrobial potentials of methanol extract of Nigerian Zingiber officinale. It was also found to be relatively safe for consumption and thus could serve as a source of candidate for the development of new antioxidants and antimicrobial drugs.

Novel vanillin derivatives: Synthesis, anti-oxidant, DNA and cellular protection properties

Antioxidants have been the subject of intense research interest mainly due to their beneficial properties associated with human health and wellbeing. Phenolic molecules, such as naturally occurring Resveratrol and Vanillin, are well known for their anti-oxidant properties, providing a starting point for the development of new antioxidants. Here we report, for the first time, the synthesis of a number of new vanillin through the reductive amination reaction between vanillin and a selection of amines. All the compounds synthesised, exhibited strong antioxidant properties in DPPH, FRAP and ORAC assays, with compounds 1b and 2c being the most active. The latter also demonstrated the ability to protect plasmid DNA from oxidative damage in the presence of the radical initiator AAPH. At cellular level, neuroblastoma SH-SY5Y cells were protected from oxidative damage (H2O2, 400 μM) with both 1b and 2c. The presence of a tertiary amino group, along with the number of vanillin moieties in the molecule contribute for the antioxidant activity. Furthermore, the delocalization of the electron pair of the nitrogen and the presence of an electron donating substituent to enhance the antioxidant properties of this new class of compounds. In our opinion, vanillin derivatives 1b and 2c described in this work can provide a viable platform for the development of antioxidant based therapeutics.

Polyphenols content and antioxidant power of fruits and leaves of Juniperus phoenicea L. From Tounfite (Morocco)

The natural antioxidants have attracted considerable attention of researchers because of their beneficial roles in human health. In the framework of the development of new antioxidants from natural sources, we are interested in this work in studying the phenolic compounds and evaluating the antioxidant properties of Juniperus phoenicea L. leaves and fruits collected in the mountains of Eastern High-Atlas (Tounfite). The phytochemical screening has allowed highlighting the existence of polyphenols, tannins, flavonoids, sterols and triterpenes, and oses and holosides in both studied samples. Mucilages are also present in these samples but in small quantities, while alkaloids and saponins are entirely absent. Extracts from leaves and fruits have been obtained by different extraction solvents: water, methanol, chloroform, ethyl acetate and n-butanol. The contents of total phenols and flavonoids were evaluated using gallic acid and quercetin as standard respectively. The ethyl acetate extracts of the leaves and fruits contain high levels of total phenolic estimated 2,91mg/g and 5,35mg/g equivalent of gallic acid (GAE) respectively. As for the flavonoid content, the ethyl acetate extracts have also reached the increased levels 11,82mg/g and 2,66mg/g equivalent of quercetin (QE). The antioxidant activities by DPPH test were quantified by spectrophotometry; the results showed that the ethyl acetate extracts from the leaves and fruits exhibit an antioxidant activity with inhibitory concentrations 50% (IC 50 ) of 94,4μg/ml and 185,83μg/ml respectively compared to that of vitamin C (47,76μg/ml). The antioxidant test allowed concluding that the leaves and fruits have a strong anti-radical activity that was assumed to be related closely to the content of polyphenols, which are generally very good antioxidants and that the leaves show a higher activity than fruits.

Insights on the antioxidant potential of 1, 2, 4-triazoles: synthesis, screening & QSAR studies.

The aligned manuscript reports synthesis, screening and QSAR analysis of twenty six 1, 2, 4-triazole analogues from their respective aromatic carboxylic acids. The structures of synthesized analogues were characterized using physical and spectral analysis. 1, 2, 4-Triazole analogs antioxidant capacity was determined using DPPH radical scavenging assay. Results revealed that out of L, T & VRT series, VRT series of 1, 2, 4-triazoles have significant antioxidant activities when compared with standard ascorbic acid. To obtain structural insights for development of new antioxidants a 2D-QSAR analysis of this dataset of 26 molecules was performed. The 2D-QSAR models correlate with the in vitro results and explain the salient structural features predominant in the molecules responsible for antioxidant activity.

Novel 2-arylbenzofuran dimers and polyisoprenylated flavanones from Sophora tonkinensis

Two novel 2-arylbenzofuran dimers, shandougenines A (1) and B (2), and two new polyisoprenylated flavanones 3 (shandougenine C) and 4 (shandougenine D) were isolated from the 95% EtOH extract of Sophora tonkinensis, together with 18 known compounds. Their structures were determined on the basis of spectral data interpretation and by comparing the spectral data with that reported previously for known compounds. Shandougenine A (1) is a unique dimeric 2-arylbenzofuran with a C-3C-5‴ bond linkage. Shandougenine B (2) is the first naturally occurring dimeric 2-arylbenzofuran with a novel C-3C-3″ bond linkage. Compound 1 showed moderate DPPH free radical scavenging capacity, whereas 2 has stronger DPPH free radical and ABTS cation radical scavenging capacity than Vc. Compounds 12, 19, and 20 showed parallel DPPH free radical scavenging capacity with Vc. Compounds 1, 3, 4, 19, 20, and 22 have parallel ABTS cation radical scavenging capacity to Vc. Compounds 1, 3, 4, and 18 showed slightly stronger superoxide anion radical scavenging capacity than the known flavanone luteolin. The antioxidant activities of shandougenines A (1) and B (2) indicated that compounds 1 and 2 may represent novel scaffolds for the development of new antioxidants.

A new generation of cysteine derivatives with three active antioxidant centers: improving reactivity and stability

The development of new antioxidants with enhanced activity constitutes a very active research field as it can contribute to the improvement of human health. Although the antioxidant activity occurs through different mechanisms, usually most of the antioxidant molecules present a unique active center which is able to react following a specific way. To overcome this weakness and in the belief that the coupling of different antioxidant groups is a good strategy to obtain multipotent antioxidants, the effect of introducing different N-protective groups on the cysteine core is evaluated by using DFT. As a result, in this work we present a multicenter antioxidant, N-(9-fluorenylmethyloxycarbonyl)cysteine methyl ester 8, able to fight efficiently through different mechanisms against free radicals independently of their nature. This antioxidant appears to be the first one of a promising new class of multipotent antioxidants with three operative centers: C(α) that is a good hydrogen donor, the Fmoc group that is a good electron donor and the all-around thiol group. Besides, its neutral radical shows a high stability due to the captodative effect in such a way that the subsequent toxic effects would be avoided. Then, its experimental radical-trapping antioxidant activity postulates compound 8 as a prototype of antioxidants more versatile and efficient than N-acetylcysteine, ascorbic acid or Trolox.

Chemometric QSAR Modeling and In Silico Design of Antioxidant NO Donor Phenols

An acceleration of free radical formation within human system exacerbates the incidence of several life-threatening diseases. The systemic antioxidants often fall short for neutralizing the free radicals thereby demanding external antioxidant supplementation. Therein arises the need for development of new antioxidants with improved potency. In order to search for efficient antioxidant molecules, the present work deals with quantitative structure-activity relationship (QSAR) studies of a series of antioxidants belonging to the class of phenolic derivatives bearing NO donor groups. In this study, several QSAR models with appreciable statistical significance have been reported. Models were built using various chemometric tools and validated both internally and externally. These models chiefly infer that presence of substituted aromatic carbons, long chain branched substituents, an oxadiazole-N-oxide ring with an electronegative atom containing group substituted at the 5 position and high degree of methyl substitutions of the parent moiety are conducive to the antioxidant activity profile of these molecules. The novelty of this work is not only that the structural attributes of NO donor phenolic compounds required for potent antioxidant activity have been explored in this study, but new compounds with possible antioxidant activity have also been designed and their antioxidant activity has been predicted in silico.

Antioxidant properties of dimethyl sulfoxide and its viability as a solvent in the evaluation of neuroprotective antioxidants

Introduction Dimethyl sulfoxide is an amphiphilic compound whose miscibility with water and its ability to dissolve lipophilic compounds make it an appreciated solvent in biomedical research. However, its reported antioxidant properties raise doubts about its use as a solvent in evaluating new antioxidants. The goal of this investigation was to evaluate its antioxidant properties and carry out a comparative study on the antioxidant properties of some known neuroprotective antioxidants in the presence and absence of dimethyl sulfoxide. Methods The antioxidant properties of dimethyl sulfoxide were studied in rat brain homogenates by determining its ability to reduce both lipid peroxidation (TBARS formation) and protein oxidation (increase in protein carbonyl content and decrease in free thiol content) induced by ferrous chloride/hydrogen peroxide. Its ability to reduce the production of hydroxyl radicals by 6-hydroxydopamine autoxidation was also estimated. The same study was also performed with three known antioxidants (α-phenyl- N- tert-butylnitrone; 2-methyl-2-nitrosopropane; 5,5-dimethyl-1-pyrroline N-oxide) in the presence and absence of dimethyl sulfoxide. Results Our results showed that dimethyl sulfoxide is able to reduce both lipid peroxidation and protein carbonyl formation induced by ferrous chloride/hydrogen peroxide in rat brain homogenates. It can also reduce the production of hydroxyl radicals during 6-hydroxydopamine autoxidation. However, it increases the oxidation of protein thiol groups caused by ferrous chloride/hydrogen peroxide in rat brain homogenate. Discussion Despite the here reported antioxidant and pro-oxidant properties of dimethyl sufoxide, the results obtained with α-phenyl- N- tert-butylnitrone, 2-methyl-2-nitrosopropane, and 5,5-dimethyl-1-pyrroline N-oxide corroborate the antioxidant properties attributed to these compounds and support the potential use of dimethyl sulfoxide as a solvent in the study of the antioxidant properties of lipophilic compounds. Conclusion Dimethyl sulfoxide is a very useful solvent that may be used at relatively low concentrations in the development of new antioxidants with neuroprotective properties.

A novel azulenyl nitrone antioxidant protects against MPTP and 3-nitropropionic acid neurotoxicities

Oxidative stress plays an important role in neuronal death in neurodegenerative disorders such as Parkinson's disease (PD) and Huntington's disease (HD). Animal models of PD or HD, produced by administration of the mitochondrial toxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 3-nitropropionic acid (3NP), respectively, show increased free radical generation. Free radicals generated in biological systems can react with spin-trapping compounds, such as nitrones, to form stable adducts. In recent years, the utility of nitrones has moved beyond analytical applications and into the realm of neuroprotection as antioxidants in both brain ischemia and models of neurodegenerative diseases. In the present study, we administered a new nitrone antioxidant, stilbazulenyl nitrone (STAZN), with either MPTP or 3NP. STAZN attenuated MPTP-induced striatal dopamine depletion by 40% and showed a tendency to dose-dependent neuroprotection. STAZN dose-dependently protected against loss of tyrosine hydroxylase immunoreactive neurons in the substantia nigra pars compacta. STAZN reduced the striatal lesion volume caused by systemic 3NP administration from 44 ± 9 to 20 ± 6 mm 3. The lipid peroxidation marker, malondialdehyde(MDA), was significantly increased in the striatum, cortex, and cerebellum of rats after administration of 3NP. These increases were blocked by co-injection of STAZN. Our data provide further evidence that STAZN is a neuroprotective free radical spin trap, and suggest that the development of new antioxidants will broaden our therapeutic strategies for neurodegenerative diseases.