A Novel Synthetic Precursor of Styryl Sulfone Neuroprotective Agents Inhibits Neuroinflammatory Responses and Oxidative Stress Damage through the P38 Signaling Pathway in the Cell and Animal Model of Parkinson’s Disease

A novel class of styryl sulfones were designed and synthesized as CAPE derivatives by our work team, which showed a multi-target neuroprotective effect, including antioxidative and anti-neuroinflammatory properties. However, the underlying mechanisms remain unclear. In the present study, the anti-Parkinson’s disease (PD) activity of 10 novel styryl sulfone compounds was screened by the cell viability test and the NO inhibition test in vitro. It was found that 4d exhibited the highest activity against PD among them. In a MPTP-induced mouse model of PD, the biological activity of 4d was validated through suppressing dopamine neurotoxicity, microglial activation, and astrocytes activation. With compound 4d, we conducted the mechanistic studies about anti-inflammatory responses through inhibition of p38 phosphorylation to protect dopaminergic neurons, and antioxidant effects through promoting nuclear factor erythroid 2-related factor 2 (Nrf2). The results revealed that 4d could significantly inhibit 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP⁺)-induced p38 mitogen-activated protein kinase (MAPK) activation in both in vitro and in vivo PD models, thus inhibiting the NF-κB-mediated neuroinflammation-related apoptosis pathway. Simultaneously, it could promote Nrf2 nuclear transfer, and upregulate the expression of antioxidant phase II detoxification enzymes HO-1 and GCLC, and then reduce oxidative damage.     

PEP-1-GLRX1 Reduces Dopaminergic Neuronal Cell Loss by Modulating MAPK and Apoptosis Signaling in Parkinson’s Disease

Parkinson’s disease (PD) is characterized mainly by the loss of dopaminergic neurons in the substantia nigra (SN) mediated via oxidative stress. Although glutaredoxin-1 (GLRX1) is known as one of the antioxidants involved in cell survival, the effects of GLRX1 on PD are still unclear. In this study, we investigated whether cell-permeable PEP-1-GLRX1 inhibits dopaminergic neuronal cell death induced by 1-methyl-4-phenylpyridinium (MPP⁺) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We showed that PEP-1-GLRX1 protects cell death and DNA damage in MPP⁺-exposed SH-SY5Y cells via the inhibition of MAPK, Akt, and NF-κB activation and the regulation of apoptosis-related protein expression. Furthermore, we found that PEP-1-GLRX1 was delivered to the SN via the blood–brain barrier (BBB) and reduced the loss of dopaminergic neurons in the MPTP-induced PD model. These results indicate that PEP-1-GLRX1 markedly inhibited the loss of dopaminergic neurons in MPP⁺- and MPTP-induced cytotoxicity, suggesting that this fusion protein may represent a novel therapeutic agent against PD.     

Dioscin-Mediated Autophagy Alleviates MPP+-Induced Neuronal Degeneration: An In Vitro Parkinson’s Disease Model

Autophagy is a cellular homeostatic process by which cells degrade and recycle their malfunctioned contents, and impairment in this process could lead to Parkinson’s disease (PD) pathogenesis. Dioscin, a steroidal saponin, has induced autophagy in several cell lines and animal models. The role of dioscin-mediated autophagy in PD remains to be investigated. Therefore, this study aims to investigate the hypothesis that dioscin-regulated autophagy and autophagy-related (ATG) proteins could protect neuronal cells in PD via reducing apoptosis and enhancing neurogenesis. In this study, the 1-methyl-4-phenylpyridinium ion (MPP⁺) was used to induce neurotoxicity and impair autophagic flux in a human neuroblastoma cell line (SH-SY5Y). The result showed that dioscin pre-treatment counters MPP⁺-mediated autophagic flux impairment and alleviates MPP⁺-induced apoptosis by downregulating activated caspase-3 and BCL2 associated X, apoptosis regulator (Bax) expression while increasing B-cell lymphoma 2 (Bcl-2) expression. In addition, dioscin pre-treatment was found to increase neurotrophic factors and tyrosine hydroxylase expression, suggesting that dioscin could ameliorate MPP⁺-induced degeneration in dopaminergic neurons and benefit the PD model. To conclude, we showed dioscin’s neuroprotective activity in neuronal SH-SY5Y cells might be partly related to its autophagy induction and suppression of the mitochondrial apoptosis pathway.     

Conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp) and its 5-methyl analog into pyridinium salts

Monoamine oxidase B metabolizes 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 1 ) first to 1-methyl-4-phenyl-2,3-dihydropyridinium salt (MPDP⁺; 5 ), and then to 1-methyl-4-phenylphridinium salt (MPP⁺; 7 ). Chemical synthesis of MPDP⁺ and its 5-methyl analog 6 was accomplished from the N-oxides 3 and 4 of MPTP and its 5-methyl analog, respectively, by a Polonovski reaction. Oxidation of MPDP⁺ to MPPM⁺ was accomplished with air, and greatly accelerated by Pt catalyst. Reduction of MPDP⁺ and MPP⁺ with NaBH₄ afforded MPTP.     

Quantification of Paraquat, MPTP, and MPP+ in brain tissue using microwave-assisted solvent extraction (MASE) and high-performance liquid chromatography–mass spectrometry

Animal models, consistent with the hypothesis of direct interaction of paraquat (PQ) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with specific areas of the central nervous system have been developed to study Parkinson’s disease (PD) in mice. These models have necessitated the creation of an analytical method for unambiguous identification and quantitation of PQ and structurally similar MPTP and 1-methyl-4-phenylpyridinium ion (MPP⁺) in brain tissue. A method for determination of these compounds was developed using microwave-assisted solvent extraction (MASE) and liquid chromatography–mass spectrometry. Extraction solvent and microwave conditions such as power and time were optimized to produce recoveries of 90% for PQ 78% for MPTP and 97% for its metabolite MPP⁺. The chromatographic separation was performed on a C8, column and detection was carried out using an ion trap as an analyzer with electrospray ionization. Mass spectrometer parameters such as heated capillary temperature, spray voltage, capillary voltage and others were also optimized for each analyte. Analysis was done in selective ion-monitoring (SIM) mode using m/z 186 for PQ, m/z 174 for MPTP, and m/z 170 for MPP⁺. The method detection limit for paraquat in matrix was 100 pg, 40 pg for MPTP, and 20 pg MPP⁺.     

Suppressing Cdk5 Activity by Luteolin Inhibits MPP+-Induced Apoptotic of Neuroblastoma through Erk/Drp1 and Fak/Akt/GSK3β Pathways

Parkinson’s disease (PD) is characterized by the progressive degeneration of dopaminergic neurons. The cause of PD is still unclear. Oxidative stress and mitochondrial dysfunction have been linked to the development of PD. Luteolin, a non-toxic flavonoid, has become interested in an alternative medicine, according to its effects on anti-oxidative stress and anti-apoptosis, although the underlying mechanism of luteolin on PD has not been fully elucidated. This study aims to investigate whether luteolin prevents neurotoxicity induction by 1-methyl-4-phenylpyridinium iodide (MPP⁺), a neurotoxin in neuroblastoma SH-SY5Y cells. The results reveal that luteolin significantly improved cell viability and reduced apoptosis in MPP⁺-treated cells. Increasing lipid peroxidation and superoxide anion (O₂⁻), including mitochondrial membrane potential (Δψm) disruption, is ameliorated by luteolin treatment. In addition, luteolin attenuated MPP⁺-induced neurite damage via GAP43 and synapsin-1. Furthermore, Cdk5 is found to be overactivated and correlated with elevation of cleaved caspase-3 activity in MPP⁺-exposed cells, while phosphorylation of Erk1/2, Drp1, Fak, Akt and GSK3β are inhibited. In contrast, luteolin attenuated Cdk5 overactivation and supported phosphorylated level of Erk1/2, Drp1, Fak, Akt and GSK3β with reducing in cleaved caspase-3 activity. Results indicate that luteolin exerts neuroprotective effects via Cdk5-mediated Erk1/2/Drp1 and Fak/Akt/GSK3β pathways, possibly representing a potential preventive agent for neuronal disorder.     

Neuroprotective Effects of B-Type Cinnamon Procyanidin Oligomers on MPP+-Induced Apoptosis in a Cell Culture Model of Parkinson’s Disease

Cinnamon procyanidin oligomers (CPOs) are water-soluble components extracted from cinnamon. This study aims to explore the neuroprotection of B-type CPO (CPO-B) against 1-methyl-4-phenylpyridinium (MPP⁺)-mediated cytotoxicity and the molecular mechanisms underlying its protection. The results demonstrated that CPO-B showed protection by increasing cell viability, attenuating an intracellular level of reactive oxygen species, downregulating cleaved caspase-3 expression, and upregulating the Bcl-2/Bax ratio. Moreover, CPO-B completely blocked the dephosphorylation of extracellular, signal-regulated kinase 1 and 2 (Erk1/2) caused by MPP⁺. Treatment with an Erk1/2 inhibitor, SCH772984, significantly abolished the neuroprotection of CPO-B against MPP⁺. Taken together, we demonstrate that CPO-B from cinnamon bark provided protection against MPP⁺ in cultured SH-SY5Y cells, and the potential mechanisms may be attributed to its ability to modulate the dysregulation between pro-apoptotic and anti-apoptotic proteins through the Erk1/2 signaling pathway. Our findings suggest that the addition of cinnamon to food or supplements might benefit patients with PD.     

Neuroprotective Activities of Boophone haemanthoides (Amaryllidaceae) Extract and Its Chemical Constituents

Parkinson’s disease (PD) is a neurodegenerative condition that progresses as age increases, and some of its major symptoms include tremor and postural and movement-related difficulties. To date, the treatment of PD remains a challenge because available drugs only treat the symptoms of the disease or possess serious side effects. In light of this, new treatment options are needed; hence, this study investigates the neuroprotective effects of an organic Boophone haemanthoides extract (BHE) and its bioactive compounds using an in vitro model of PD involving the toxin 1-methyl-4-phenylpyridinium (MPP⁺) and SH-SY5Y neuroblastoma cells. A total of seven compounds were isolated from BHE, viz distichamine (1), 1α,3α-diacetylnerbowdine (2), hippadine (3), stigmast-4-ene-3,6-dione (4), cholest-4-en-3-one (5), tyrosol (6), and 3-hydroxy-1-(4′-hydroxyphenyl)-1-propanone (7). Six compounds (1, 2, 4, 5, 6 and 7) were investigated, and five showed neuroprotection alongside the BHE. This study gives insight into the bioactivity of the non-alkaloidal constituents of Amaryllidaceae, since the isolated compounds and the BHE showed improved cell viability, increased ATP generation in the cells as well as inhibition of MPP⁺-induced apoptosis. Together, these findings support the claim that the Amaryllidaceae plant family could be a potential reserve of bioactive compounds for the discovery of neuroprotective agents.     

Neuroprotective Activities of Crossyne flava Bulbs and Amaryllidaceae Alkaloids: Implications for Parkinson’s Disease

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and affects approximately 6.3 million people worldwide. To date, the treatment of PD remains a challenge, as available treatment options are known to be associated with serious side effects; hence, the search for new treatment strategies is critical. Extracts from the Amaryllidaceae plant family as well as their alkaloids have been reported to have neuroprotective potentials. This study, therefore, investigated the biological activities of Crossyne flava and its isolated alkaloids in an in vitro MPP⁺ (1-methyl-4-phenylpyridinium) PD model using SH-SY5Y cells. The effects of the total extract as well as the four compounds isolated from Crossyne flava (i.e., pancratinine B (1), bufanidrine (2), buphanisine (3), and epibuphanisine (4)) were evaluated for cell viability, neuroprotection, levels of reactive oxygen species (ROS), adenosine triphosphate activity (ATP), and caspase 3/7 activity in SH-SY5Y cells. The results obtained showed that pre-treatment with both the extract and the isolated compounds was effective in protecting the SH-SY5Y cells from MPP⁺-induced neurotoxicity and inhibited ROS generation, ATP depletion as well as apoptosis induction in the SH-SY5Y cells. The results of this study show that the Amaryllidaceae plant family may be a source of novel compounds for the treatment of neurodegenerative diseases, which validates the reported traditional uses.     

Neuroprotective Effect of Dioscin against Parkinson’s Disease via Adjusting Dual-Specificity Phosphatase 6 (DUSP6)-Mediated Oxidative Stress

Exploration of lead compounds against Parkinson’s disease (PD), a neurodegenerative disease, is of great important. Dioscin, a bioactive natural product, shows various pharmacological effects. However, the activities and mechanisms of dioscin against PD have not been well investigated. In this study, the tests on 6-hydroxydopamine (6-OHDA)-induced PC12 cells and rats were carried out. The results showed that dioscin dramatically improved cell viability, decreased reactive oxygen species (ROS) levels, improved motor behavior and tyrosine hydroxylase(TH) levels and restored the levels of glutathione (GSH) and malondialdehyde (MDA) in rats. Mechanism investigation showed that dioscin not only markedly increased the expression level of dual- specificity phosphatase 6 (DUSP6) by 1.87-fold in cells and 2.56-fold in rats, and decreased phospho-extracellular regulated protein kinases (p-ERK) level by 2.12-fold in cells and 2.34-fold in rats, but also increased the levels of nuclear factor erythroid2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), superoxide dismutase (SOD) and decreased the levels of kelch-1ike ECH-associated protein l (Keap1) in vitro and in vivo. Furthermore, DUSP6 siRNA transfection experiment in PC12 cells validated the protective effects of dioscin against PD via regulating DUSP6 to adjust the Keap1/Nrf2 pathway. Our data supported that dioscin has protection against PD in regulating oxidative stress via DUSP6 signal, which should be considered as an efficient candidate for the treatment of PD in the future.     

Quantum dots protect against MPP+-induced neurotoxicity in a cell model of Parkinson’s disease through autophagy induction

Autophagy is a basic cellular process that decomposes damaged organelles and aberrant proteins. Dysregulation of autophagy is implicated in pathogenesis of neurodegenerative disorders, including Parkinson's disease(PD). Pharmacological compounds that stimulate autophagy can provide neuroprotection in models of PD. Nanoparticles have emerged as regulators of autophagy and have been tested in adjuvant therapy for diseases. In this present study, we explore the effects of quantum dots(QDs) that can induce autophagy in a cellular model of Parkinson's disease. Cd Te/Cd S/Zn S QDs protect differentiated rat pheochromocytoma PC12 cells from MPP+-induced cell damage, including reduced viability, apoptosis and accumulation of α-Synuclein, a characteristic protein of PD. The protective function of QDs is autophagy-dependent. In addition, we investigate the interaction between quantum dots and autophagic pathways and identify beclin1 as an essential factor for QDs-induced autophagy. Our results reveal new promise of QDs in the theranostic of neurodegenerative diseases.     

Electronic and Conformational Effects on the Lipophilicity of Isomers and Analogs of the Neurotoxin 1-Methyl-4-phenylpyridinium (MPP+)

A number of isomers and analogs of the neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺) were examined for their lipophilic behavior. Their partition coefficients in the 1-octanol/H₂O system were measured by centrifugal partition chromatography (CPC), which, being much faster and markedly more precise than the classical shake-flask method, proved a very promising alternative for assessing lipophilicity. A smaller-than-expected lipophilicity was shown by the ortho-isomer of MPP⁺ (M2PP⁺) and is explained in terms of electronic effects and rigidity, as revealed by UV and NMR spectroscopy, and conformational analysis. Implications of lipophilicity in modulating the in vivo dopaminergic neurotoxicity of the examined compounds are also discussed.     

Relationship between Neuroprotective Effects and Structure of Procyanidins

This study evaluated the relationship between the neuroprotective effects of procyanidins and their structural characteristics. In vitro, a rat pheochromocytoma cell line (PC12) was exposed to the grape seed-derived procyanidin monomers: catechin (C), epicatechin (EC), and epicatechin gallate (ECG); the procyanidin dimers: procyanidin B1 (B1), procyanidin B2 (B2), procyanidin B3 (B3), procyanidin B4 (B4), procyanidin B1-3-O-gallate (B1-G), and procyanidin B2-3-O-gallate (B2-G); and the procyanidin trimers: procyanidin C1 (C1) and N-acetyl-l-cysteine (NAC) for 24 h. Cells were then incubated with 200 μM H₂O₂ for 24 h. In vivo, zebrafish larvae (AB strain) 3 days post-fertilization were incubated with NAC or procyanidins (C, EC, ECG, B1, B2, B3, B4, B1-G, B2-G, C1) in 300 µM H₂O₂ for 4 days. Different grape seed procyanidins increased the survival of PC12 cells challenged with H₂O₂, improved the movement behavior disorder of zebrafish caused by H₂O₂, inhibited the increase of ROS and MDA and the decrease of GSH-Px, CAT, and SOD activities, and up-regulated the Nrf2/ARE pathway. The neuroprotective effects of the procyanidin trimer C1 treatment group were greater than the other treatment groups. These results suggest that the neuroprotective effect of procyanidins is positively correlated with their degree of polymerization.     

Increased phosphatidylcholine (16:0/16:0) in the folliculus lymphaticus of Warthin tumor

Warthin tumor (War-T), the second most common benign salivary gland tumor, consists mainly of neoplastic epithelium and lymphoid stroma. Some proteins and genes thought to be involved in War-T were evaluated by molecular biology and immunology. However, lipids as an important component of many tumor cells have not been well studied in War-T. To elucidate the molecular biology and pathogenesis of War-T, we investigated the visualized distribution of phosphatidylcholines (PCs) by imaging mass spectrometry (IMS). In our IMS analysis of a typical case, 10 signals were significantly different in intensity (p?+ (m/z 772.5), [PC (16:0/20:4)?+?K]⁺ (m/z 820.5), [PC (16:0/20:3)?+?K]⁺ (m/z 822.5), [PC (18:2/20:4)?+?K]⁺ (m/z 844.5), and [PC (18:0/20:5)?+?K]⁺ (m/z 846.5). PC (16:0/16:0) was increased specifically in the folliculus lymphaticus of War-T lymphoid stroma, suggesting a different metabolism. Localization of PC (16:0/16:0) might reflect inflammation activity participating in the pathogenesis of War-T. Thus, our IMS analysis revealed the profile of PCs specific to the War-T region. The molecules identified in our study provide important information for further studies of War-T pathogenesis.     

Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation

Phenolic compounds are thought to be important to prevent neurodegenerative diseases (ND). Parkinson’s Disease (PD) is a neurodegenerative disorder known for its typical motor features, the deposition of α-synuclein (αsyn)-positive inclusions in the brain, and for concomitant cellular pathologies that include oxidative stress and neuroinflammation. Neuroprotective activity of fisetin, a dietary flavonoid, was evaluated against main hallmarks of PD in relevant cellular models. At physiologically relevant concentrations, fisetin protected SH-SY5Y cells against oxidative stress overtaken by tert-butyl hydroperoxide (t-BHP) and against methyl-4-phenylpyridinuim (MPP⁺)-induced toxicity in dopaminergic neurons, the differentiated Lund human Mesencephalic (LUHMES) cells. In this cellular model, fisetin promotes the increase of the levels of dopamine transporter. Remarkably, fisetin reduced the percentage of cells containing αsyn inclusions as well as their size and subcellular localization in a yeast model of αsyn aggregation. Overall, our data show that fisetin exerts modulatory activities toward common cellular pathologies present in PD; remarkably, it modulates αsyn aggregation, supporting the idea that diets rich in this compound may prove beneficial.     

Antidiabetic and Renoprotective Effects of Coffea arabica Pulp Aqueous Extract through Preserving Organic Cation Transport System Mediated Oxidative Stress Pathway in Experimental Type 2 Diabetic Rats

Coffea arabica pulp (CP) is a by-product of coffee processing. CP contains polyphenols that have exhibited beneficial effects, including antioxidant and lipid-lowering effects, as well as enhanced insulin sensitivity, in in vitro and in vivo models. How polyphenols, as found in CP aqueous extract (CPE), affect type 2 diabetes (T2D) has not been investigated. Thus, the present study examined the potential antidiabetic, antioxidant, and renoprotective effects of CPE-rich polyphenols, using an experimental model of T2D in rats induced by a high-fat diet and a single low dose of streptozotocin. The T2D rats received either 1000 mg/kg body weight (BW) of CPE, 30 mg/kg BW of metformin (Met), or a combination treatment (CPE + Met) for 3 months. Plasma parameters, kidney morphology and function, and renal organic transport were determined. Significant hyperglycemia, hypertriglyceridemia, insulin resistance, increased renal lipid content and lipid peroxidation, and morphological kidney changes related to T2D were restored by both CPE and CPE + Met treatments. Additionally, the renal uptake of organic cation, ³H-1-methyl-4-phenylpyridinium (MPP⁺), was reduced in T2D, while transport was restored by CPE and CPE + Met, through an up-regulation of antioxidant genes and protein kinase Cα deactivation. Thus, CPE has antidiabetic and antioxidant effects that potentially ameliorate kidney function in T2D by preserving renal organic cation transport through an oxidative stress pathway.     

Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells

A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a–5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer’s disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aβ_25-35-induced PC12 cells at 5 μg/mL. We found that compound 5c was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ_25-35-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ_25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ_25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3β/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.     

Anticarcinogenic and Antioxidant Action of an Edible Aquatic Flora Jussiaea repens L. Using In Vitro Bioassays and In Vivo Zebrafish Model

Oxidative stress is the major cause of many health conditions, and regular consumption of antioxidants helped to encounter and prevent such oxidative stress-related diseases. Due to safety concerns over long-term uses of synthetic antioxidants, natural antioxidants are more preferred. The purpose of this study is to investigate the antioxidant and anticancer activities of Jussiaea repens L., a wild edible flora found in Manipur, India. The antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), Ferric reducing antioxidant power (FRAP) assay and DNA-nicking assay. The anticancer activity was tested using five cancer lines viz., SKOV3 cells (ovarian), HeLa (cervical), MDA-MB-231 (breast), PANC-1 (pancreatic), and PC3 (prostate). The toxicity, developmental effect, antiproliferative activity was further tested using zebrafish embryos. The methanolic plant extract had higher polyphenol content than flavonoids. The in vitro study demonstrated a promising antioxidant capacity and DNA protection ability of this plant. The extract also showed cytotoxic activity against SKOV3, HeLa, MDA-MB-23, and PANC-1 cancer cell lines. The in vivo studies on zebrafish embryos demonstrated the extract’s ability to suppress the developmental process and elicited more cytotoxicity to cancer cells than developing zebrafish embryos. Moreover, the in vivo studies on zebrafish embryos also indicated the antiproliferative activity of J. repens L. extract.     

Synthesis,structure, electrochemical properties,and antioxidant activities of copper(II) and zinc(II) complexes with N,N-bis(N-ethyl-2-ylmethylbenzimidazol)allylamine ligand

N,N-bis(N-methyl-2-ylmethylbenzimidazole)aniline (EtAIDB) and its transition metal complexes, [Cu(EtAIDB)Br₂]·EtOH {dibromo[N,N-bis(N-methyl-2-ylmethylbenzimidazole)aniline] copper(II) ethanol} (1) and [Zn(EtAIDB)Br₂] {dibromo[N,N-bis(N-methyl-2-ylmethylbenzimidazole)aniline] zinc(II)} (2), have been synthesized and characterized by elemental analysis, molar conductivity, UV–visible, and IR spectroscopy. The X-ray crystallographic studies of 1 and 2 have shown two different arrangements: 1 is distorted square-based pyramidal, while 2 can be treated as distorted tetrahedral. The cyclic voltammogram of 1 represents quasi-reversible Cu²⁺/Cu⁺ pairs. In vitro antioxidant tests showed that 1 had significant antioxidant activity against superoxide and hydroxy radicals.