Human Peroxiredoxin Research Articles

Design, characterization, and bioactivity evaluation of novel symmetrical N,N'-benzene-1,2-diylbis[1-(2-chloroquinolin-3-yl)methanimine] based metal complexes

This study presents the synthesis and characterization of two novel metal complexes derived from the symmetrical Schiff base N,N'-benzene-1,2-diylbis[1-(2-chloroquinolin-3-yl)methanimine] (OBCQ), coordinated with Nickel(II) (NiOBCQ) and Copper(II) (CuOBCQ). The structural elucidation of these complexes was achieved through a comprehensive suite of analytical techniques, including elemental analysis, UV–visible spectroscopy, mass spectrometry, infrared spectroscopy, magnetic susceptibility, conductivity measurements, and thermal analysis. The data confirm that both NiOBCQ and CuOBCQ adopt octahedral geometries, formulated as [Ni(OBCQ)(H₂O)₂(Cl)₂] and [Cu(OBCQ)(H₂O)₂(Cl)₂], respectively. Density Functional Theory (DFT) calculations were employed to validate the molecular structures and explore the quantum chemical parameters of OBCQ and its metal complexes. Additionally, in vitro assessments of anti-inflammatory and antioxidant activities revealed enhanced bioactivity for the metal complexes compared to the free OBCQ ligand. Molecular docking studies against key proteins (5IKT for Human Cyclooxygenase-2 and 5IJT for Human Peroxiredoxin 2) highlighted strong binding affinities and molecular interactions, suggesting that OBCQ and its metal complexes hold significant promise as novel therapeutic agents with multifaceted biological activities.

Synthesis, Characterization and Computational Studies on (E)-4-(1-((2-hydroxyphenyl)imi no) hexyl)-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one

A coupling precursor, 4-hexanoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, 1 synthesized by the reaction of 3-methyl-1-phenyl-1H-pyrazol-5-one with hexanoyl chloride was reacted with 2-aminophenol to synthesize (E)-4-(1-((2-hydroxyphenyl)imino)hexyl)-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, 1a. The compounds were characterized by conventional spectroscopic techniques, 1H and 13C NMR, UV-Visible, FTIR spectroscopy and single crystal X-ray crystallograpic structural determinations and computational techniques. To augment the experimental data, DFT calculations were carried. Molecular dockings were used to predict the interactions between, 1a with some biological targets. The binding free energies in the Plasmepsin II active sites indicated anti−malarial activity against P. falciparum in epidermal growth factor receptor (EGFR) inhibition, anti-inflammatory properties against human peroxiredoxin 5, and anticancer properties. With binding energies less than −5.00 kcal/mol, the results indicate that 1a is a potential drug target for anti-inflammatory, anti-malarial and anti-cancer properties.

Synthesis, Characterization, and Therapeutic Potential of Novel Schiff Base Metal Complexes: Nickel(II) and Copper(II) Complexes Based 2‐[(2‐Chloroquinolin‐3‐yl)methylidene]aminobenzenethiol (CQAT)

ABSTRACTThis research focused on the design and comprehensive characterization of two novel transition metal complexes derived from the symmetrical Schiff base 2‐[(2‐chloroquinolin‐3‐yl)methylidene]aminobenzenethiol (CQAT), coordinated with nickel(II) (NiCQAT) and copper(II) (CuCQAT) ions. The structural elucidation of these complexes was achieved through a range of advanced analytical techniques. Thermal analysis revealed the stability and decomposition patterns of the complexes, supporting the identification of their coordination geometries. The collective data indicated that both NiCQAT and CuCQAT complexes adopt octahedral coordination, with the specific formulas [Ni(CQAT)2(H2O)2] and [Cu(CQAT)2(H2O)2], respectively. To complement the experimental findings, density functional theory (DFT) calculations were employed. These theoretical calculations confirmed the proposed molecular structures and provided detailed insights into key quantum chemical parameters, such as HOMO–LUMO energies, molecular orbitals, and electronic distributions, which are crucial for understanding the complexes' reactivity and stability. Furthermore, extensive in vitro biological evaluations were conducted to assess the anti‐inflammatory and antioxidant properties of the synthesized complexes. These assays demonstrated that both NiCQAT and CuCQAT exhibited significantly enhanced bioactivity compared to the free CQAT ligand, suggesting a synergistic effect of metal coordination on the ligand's biological efficacy. To further explore the mode of action, molecular docking studies were performed targeting two key proteins—human cyclooxygenase‐2 (PDB ID: 5IKT) and human peroxiredoxin 2 (PDB ID: 5IJT). The docking simulations provided valuable insights into the binding affinities, interaction energies, and key amino acid residues involved in the binding process, offering a molecular‐level understanding of their potential biological mechanisms. The findings from these multidisciplinary studies highlight the therapeutic potential of CQAT and its nickel and copper complexes, positioning them as promising candidates for further development in the field of medicinal chemistry.

In Vitro Antioxidant and Antifungal Activities of Extracts from Ocimum basilicum Leaves Validated by Molecular Docking and ADMET Analysis.

The aim of study is to investigate the various mechanism-based antioxidant and anti-fungal properties of a hydroalcoholic extract of Ocimum basilicum L leaves. Additionally, conduct molecular docking to simultaneously validate in vitro activities. Also, perform ADMET analysis to know pharmacokinetic properties and its toxicity for its safety. Prior extract's qualitative analysis has been performed to identify the bioactive compounds by phytochemical tests and GC-MS analysis. Different mechanism-based in vitro antioxidant methods are studied; in different methods, different IC50 values have come, which revealed the extract's antioxidant potentials. The antifungal potential of the extract has been observed by performing a modified poison food assay and a time-killing curve assay. In silico analysis with the human peroxiredoxin 5 enzyme (PDB ID: 1HD2) and secreted aspartic proteinase (PDB ID: 2QZX), which predict extract biological activity, has shown promising results of Ocimum basilicum L extract. In silico findings confirm the in vitro experimental outcome of the extract. The different IC50 values of extracts in different mechanisms indicate their therapeutic potential, and that encourages further research in formulation development. The time-killing assay method gives information about a dynamic interaction between extract and microbial strain. Concentration-dependent antifungal studies have significance in formulation development for dose determination.

Antioxidant, xanthine oxidase (XO) inhibitory, hypouricemic effect evaluation and GCMS analysis of ethanolic extract of Piper chaba stem: Supported by in vitro, in vivo, and molecular docking experiments

BackgroundPiper chaba has been traditionally using for its potential health benefits. The principal goal of this investigation was to assess the pharmacological characteristics of the EEPCS, focusing on investigating its potential antihyperuricemic effects, ability to inhibit xanthine oxidase (XO) enzyme, and antioxidant properties. MethodsThe antioxidant capability of the extract was assessed using the DPPH radical assay. The extract was evaluated in vitro aimed at its xanthine oxidase inhibitory (XOI) action and further experimented for its antihyperuricemic effect on the Potassium oxonate (PO) induced hyperuricemia murine model. Besides, molecular docking techniques were employed to interpret the inhibitory mechanism of the compounds identified through GCMS analysis of the EEPCS. ResultsThere was no safety concern at doses up to 3000 mg/kg of the extract as confirmed by mice model studies. The extract displayed potent the antioxidant properties during quantitative antioxidant test (IC50=104.9 ± 0.99 µg/mL). In XOI test, the extract was found to be effective with an IC50 value of 26.14 μg/mL. In addition, the extract was found to decrease the Serum uric acid (SUA) levels by 36.72 and 61.84 % at 100 and 200 mg/kg body weight respectively, compared to the hyperurecaemic animals. The GCMS analysis of the extract revealed eighteen distinct compounds, which were docked against human peroxiredoxin 5 and xanthin oxidase proteins. Selina-3,7(11)-diene (CID: 6429221) was the most effective phytochemical for the human peroxiredoxin 5 protein having binding score −6.2 Kcal/mol compared to standard ascorbic acid (5.6 Kcal/mol). Besides, gamma-muurolene (-7.9 Kcal/mol) was the most effective phytochemical for the XO protein compared to standard allopurinol (−6.4 Kcal/mol). ConclusionOur experimental data showed that the EEPCS has potentiality as an antioxidant and hypouricemic agent that could be contributed to treat and manage oxidative stress (OS), gout and hyperuricemia.

Phytochemical profiling, molecular docking, and ADMET evaluation of essential oils from Anaphalis busua and Anaphalis margaritacea in Uttarakhand's Himalayan Terrain

BackgroundThe study focuses on a comparative analysis of essential oils derived from two species of the Anaphalis genus, namely Anaphalis busua and Anaphalis margaritacea, collected at varying elevations in the hilly terrain of Uttarakhand. The investigation aims to explore the phytochemical composition, conduct in silico molecular docking studies, and evaluate ADMET properties of the essential oils to understand their potential bioactivity. MethodsEssential oils were extracted from the whole plants using the hydrodistillation method, and GC–MS was employed for compound identification. A total of 31 compounds were identified in A. busua and 32 in A. margaritacea, constituting 87.86 % and 87.83 % of the total composition, respectively. Major compounds included isocaryophyllene, caryophyllene oxide, geranyl-α-terpinene, α-pinene, γ-muurolene, δ-cadinene, humulene, and copaene. ResultsMolecular docking studies were conducted using PyRx software on ten notable compounds as ligands, targeting cyclooxygenase-2 (COX-2) and human peroxiredoxin 5 to assess antioxidant and anti-inflammatory activities. Isocaryophyllene, with concentrations of 14.07 % (A. busua) and 17.82 % (A. margaritacea), exhibited significant binding affinities of -5.7 and -7.2 kcal/mol against 1HD2 and 4COX, respectively. ConclusionThe research provides valuable insights into the chemical composition of essential oils from Anaphalis plants and validates their bioactive potential through in silico analysis. Isocaryophyllene emerges as a key compound with noteworthy binding affinities, emphasizing its importance in the medicinal and pharmacological applications of essential oils derived from A. busua and A. margaritacea. The results enhance our understanding of the therapeutic potential of Anaphalis essential oils, opening avenues for future research in natural products and drug discovery.

Fabrication, structural, DFT, biological and molecular docking studies of Fe(III), Ni(II), and Cu(II) complexes based on Schiff-base derived from benzene-1,4-diamine and 2-hydroxy-1-naphthaldehyde

This study presents the design & comprehensive characterization of three novel metal complexes derived from a Schiff base compound (H2PDN) synthesized from benzene-1,4-diamine and 2-hydroxy-1-naphthaldehyde, coordinated with Fe (III) (FePDN), Ni (II) (NiPDN), & Cu (II) (CuPDN). Structures of both the H2PDN ligand & its metal complexes were proposed utilizing various analytical methods, having elemental analysis, ultraviolet–visible spectroscopy, mass spectrospcopy, infrared spectroscopy, magnetic properties, conductivity measurement, & thermal analysis. The obtained data revealed octahedral geometries for both FePDN and CuPDN complexes, denoted as [Fe2(PDN)(H2O)4(Cl)4] and [Cu2(PDN)(H2O)6(Cl)2], respectively, while the NiPDN complex exhibited a distorted tetrahedral structure, represented as [Ni2(PDN)(H2O)2(Cl)2]. Density functional theory (DFT) computations were employed to validate the molecular structures & explore quantum chemical parameters of both H2PDN & its metal complexes. The synthesized H₂PDN Schiff base and its metal complexes (FePDN, NiPDN, CuPDN) showcased significant antimicrobial, anti-inflammatory, and antioxidant activities. NiPDN exhibited the highest inhibition zone against P. aeruginosa (21.44 ± 0.28 mm) and S. aureus (19.37 ± 0.40 mm), while CuPDN showed strong inhibition against E. coli (18.42 ± 0.13 mm). NiPDN demonstrated excellent antibacterial efficacy with a low MIC against B. cereus (21.00 ± 0.98 μM), and CuPDN displayed potent anti-inflammatory (IC50: 121.65 μM) and antioxidant activity (IC50: 84.7 ± 0.77 μM). These results indicate the therapeutic potential of the H₂PDN complexes. Molecular docking studies targeting specific proteins (2VF5 for Escherichia coli, 3CKU for Aspergillus flavus, 5IKT for Human Cyclooxygenase-2, & 5IJT for human peroxiredoxin 2) were performed to assess the binding affinities & interactions of H2PDN & its metal complexes. The results propose promising potential for the application of H2PDN and its metal complexes as novel therapeutic agents with diverse biological activities.

Unravelling the Phytochemical Composition and Antioxidant Potential of Different Parts of Rumex vesicarius L.: A RP-HPLC-MS-MS/MS, Chemometrics, and Molecular Docking-Based Comparative Study.

Rumex vesicarius L. Polygonaceae is a wildly grown plant in Egypt, North Africa, and Asia with wide traditional uses. Several studies reported its biological activities and richness in phytochemicals. This research addresses a comprehensive metabolic profiling of the flowers, leaves, stems, and roots via RP-HPLC-QTOF-MS and MS/MS with chemometrics. A total of 60 metabolites were observed and grouped into phenolic acids, flavonoids, phenols, terpenes, amino acids, fatty acids, organic acids, and sugars. Principal component analysis and hierarchal cluster analysis showed the segregation of different parts. Moreover, the antioxidant capacity was determined via several methods and agreed with the previous results. Additionally, an in silico approach of molecular docking of the predominant bioactive metabolites was employed against two antioxidant targets, NADPH oxidase and human peroxiredoxin 5 enzyme (PDB ID: 2CDU and 1HD2) receptors, alongside ADME predictions. The molecular modelling revealed that most of the approached molecules were specifically binding with the tested enzymes, achieving high binding affinities. The results confirmed that R. vesicarius stems and roots are rich sources of bioactive antioxidant components. To our knowledge, this is the first comprehensive metabolic profiling of R. vesicarius giving a prospect of its relevance in the development of new naturally based antioxidants.

Selenocysteine variant of human Peroxiredoxin 2 is more active than the wild type enzyme

Selenocysteine variant of human Peroxiredoxin 2 is more active than the wild type enzyme

Antioxidant Activity Properties of Extract of Turmeric (Curcuma longa L.) Plant

In this study, it was aimed to determine the chemical components in the ethanol extract of the turmeric (Curcuma longa L.) plant rhizomes sold as powder in spice-sellers and to determine its antioxidant activity properties. For this purpose, turmeric rhizomes powder was extracted by maceration method using ethanol solvent and its chemical content was determined by Gas chromatography-Mass spectrometry (GC-MS) analysis. After chemical components were determinate for the turmeric ethanol extract, the inhibitory activities of these chemicals against the Crystal structure of Human peroxiredoxin 5 (HP5) (PDB ID: 1HD2) and Bovine Xanthine Oxidase (BXO) (PDB ID: 3NRZ) downloaded from the Protein Data Bank site were compared. The highest activity of the molecule was investigated by Gaussian calculations.

Polygonum aviculare L.'s biological Activities: Investigating its Anti-Proliferative, Antioxidant, chemical properties supported by molecular docking study

In this study, two different solvent extracts of Polygonum aviculare L. collected from natural environment were evaluated in terms of their antioxidant properties, antiproliferative properties and interactions of the extract components with proteins, and were addressed in terms of their pharmacological potential and biological activities. The plant was extracted using two different solvents, and its biological activity levels were examined utilizing in vitro antioxidant and antiproliferative (cytotoxicity assay) assays. According to the results obtained, there was a variation in chemical composition between the water and methanol extracts of this plant. While “1,4:3,6-Dianhydro-.alpha.-d-glucopyranose” was determined with 2.78 as the major component of the water extract of the plant, “n-Hexadecanoic acid” was determined with 10.32 in the methanol extract. The antioxidant activity of the plant was evaluated according to both DPPH and ABTS methods. The results obtained in both methods were found to be close to each other. While the antioxidant activity value of the plant remained at a moderate level compared to the standard substance, it was observed that the activity value increased as the concentration increased. When the results were examined in terms of antiproliferative properties of aqueous and methanolic extracts, it was seen that only the water extract was active. In addition, among the molecules identified in the extracts, it was determined by molecular docking calculations that cyclododecane, which is the third most abundant component in the methanol extract, showed the highest biological activity. In the same time, the activities of chemicals found in Polygonum aviculare L. plant extract against a range of proteins, including the crystal structures of the following: bovine xanthine oxidedase (PDB ID: 3NRZ), human peroxiredoxin 5 (PDB ID: 1HD2), antibacterial FabH inhibitors (PDB ID: 4Z8D), estrogen receptor (PDB ID: 1A52), and the BRCT repeat region (PDB ID: 1JNX). Next, the compounds with the highest activity were analyzed for their ADME/T characteristics.

Designing, DFT, biological, & molecular docking analysis of new Iron(III) & copper(II) complexes incorporating 1-{[-(2-Hydroxyphenyl)methylene]amino}−5,5-diphenylimidazolidine-2,4-dione (PHNS)

The exploration encompassed the synthesis and characterization of two innovative complexes, namely FePHNS and CuPHNS, employing a diverse array of analytical techniques such as elemental analysis, infrared and ultraviolet-visible spectroscopy, mass spectrometry, molar conductivity measurements, magnetic susceptibility assessments, and thermal analysis (TGA). In the spectral domain, infrared spectroscopy substantiated the tridentate ONS coordination of the PHNS ligand to the central metal atom. Thermal analysis offered valuable insights into the distribution and content of water molecules within the complexes. Density functional theory (DFT) calculations were harnessed to validate the molecular structures of both the PHNS ligand and its complex entities, providing an intricate comprehension of their quantum chemical parameters. The investigation extended to an evaluation of the in vitro antibacterial, antifungal, and antioxidant efficacy of the PHNS ligand and its complexes, revealing heightened biological activities for the complexes in comparison to the free PHNS ligand, notably with the CuPHNS complex demonstrating the highest activity, while the PHNS ligand exhibited the lowest. To delve into potential physiological activities, molecular docking studies were conducted, predicting the binding affinity of the compounds to proteins 2vf5 (Glucosamine-6-phosphate synthase in complex with glucosamine-6-phosphate) from Escherichia coli, 3cku (rate oxidase from Aspergillus flavus complexed with its inhibitor 8-azaxanthin and chloride) from Aspergillus flavus, and 5IJT (Crystal structure of Human Peroxiredoxin 2 Oxidized). The ensuing analysis of protein-ligand interactions and binding energies underscored the promising physiological activities of the investigated compounds, warranting further exploration for their potential in novel drug development.

Milk thistle extracts could enhance the UV-protection efficiency and stability of mineral filters in sunscreen formulations

This paper was aimed to determine the total silymarin content, total antioxidant capacity, free radical scavenging activity of methanolic extracts obtained by ultrasonic assisted extraction of defatted milk thistle fruits, as well as to evaluate the sunscreen activity of the cream formulation containing milk thistle extract (MTE) using in vitro SPF method. Antibacterial and antibiofilm effect of extract was also evaluated. Moreover, the probable mode of action for the antioxidant activity of the extract detected via the in vitro assay was explored through molecular docking and molecular dynamics (MD) simulation. The total amount of silymarin in MTE was determined spectrophotometrically as silibinin equivalent. While the total antioxidant capacity of MTE and cream containing MTE was determined by the copper ions (Cu2+) reducing antioxidant capacity (CUPRAC) method, the radical scavenging capacity was determined by the 1,1-diphenyl-2-picryl-hydrazil (DPPH) method. Total tocopherol content was determined spectrophotometrically. In the present study, the amount of silymarin in the MTE was determined as 330.19 ± 1.95 mg silibinin equivalent/g-extract. The CUPRAC and DPPH values of MTE were calculated to be 2.49 ± 0.03, 0.675 ± 0.0006 mmol TE/g-extract, respectively, while the CUPRAC and DPPH values of the cream containing MTE were 0.327 ± 0.003, 0.156 ± 0.0006 mmol TE/g-cream, respectively. The total tocopherol content of the oils of milk thistle fruits was found to be 383.43 mg/kg oil. According to microbial tests results the MIC values of S. aureus and E. coli was detected 0.15625 and 0.3125, respectively. And inhibition rate of extract on biofilm formation on P. aeruginosa PAO1 was found 33 % rate. The molecular docking study demonstrated that the major constituent, silibinin, had a high potential of binding to the human peroxiredoxin 5. On the other hand, the MD simulation of the enzyme-silibinin complex revealed that the compound could be unstable in the binding region of the enzyme. The addition of MTE, which has antioxidant properties, to creams improved its effectiveness on sun protection and contributed to obtaining high SPF values. At the end of day 28 under accelerated test conditions, the combination of ZnO and MTE exhibited greater ability for sun protection compared to the cream containing ZnO as a sun filter agent. Additionally, milk thistle extracts is an ideal filter agent as an ingredient in sunscreens.

Phytochemical Content of Malus floribunda: In Vitro and Molecular Docking Studies.

Malus floribunda Siebold ex Van Houtte is a plant planted for landscaping, and its sour and red fruits have been seen to be frequently used in the treatment of diabetes, making vinegar marmalade, and producing natural food dyes. Apart from these usage areas of this plant, it is aimed at determining the phytochemical content. For this purpose, plant parts (fruit, leaf, and branch) were examined. The antioxidant capacity (vitamins A, E, and C, lycopene, beta-carotene, total phenolic and flavonoid amounts, and DPPH radical scavenging effect), antimicrobial activity (agar well diffusion method, minimum inhibitory concentration-MIC), and GC-MS contents of plant parts were determined. High-performance liquid chromatography (HPLC), spectrophotometers, and gas chromatography/mass spectroscopy (GC-MS) methods were used in the study. It was determined that M. floribunda fruit is rich in lycopene, beta-carotene, and antioxidant vitamins and contains many biomolecules. In addition, it was concluded that the extracts of different parts of the plant have antimicrobial activity. This study has revealed the idea that this plant, whose phytochemical, antioxidant, and antimicrobial content has been determined, can be used as a bioactive substance equivalent to antibiotics in medicine, the food industry, and human nutrition. In addition, it is expected that the study will contribute to the plant literature. Molecular docking studies were performed to evaluate the binding interactions between the compound and human peroxiredoxin 5 and S. aureus. Both in vitro and in silico results indicated that synthesized extracts could act as potent antioxidant and antimicrobial agents.

The architecture of redox microdomains: Cascading gradients and peroxiredoxins’ redox-oligomeric coupling integrate redox signaling and antioxidant protection

In the cytosol of human cells under low oxidative loads, hydrogen peroxide is confined to microdomains around its supply sites, due to its fast consumption by peroxiredoxins. So are the sulfenic and disulfide forms of the 2-Cys peroxiredoxins, according to a previous theoretical analysis [Travasso et al., Redox Biology 15 (2017) 297]. Here, an extended reaction-diffusion model that for the first time considers the differential properties of human peroxiredoxins 1 and 2 and the thioredoxin redox cycle predicts important new aspects of the dynamics of redox microdomains. The peroxiredoxin 1 sulfenates and disulfides are more localized than the corresponding peroxiredoxin 2 forms, due to the former peroxiredoxin's faster resolution step. The thioredoxin disulfides are also localized. As the H2O2 supply rate (vsup) approaches and then surpasses the maximal rate of the thioredoxin/thioredoxin reductase system (V), these concentration gradients become shallower, and then vanish. At low vsup the peroxiredoxin concentration determines the H2O2 concentrations and gradient length scale, but as vsup approaches V, the thioredoxin reductase activity gains influence. A differential mobility of peroxiredoxin disulfide dimers vs. reduced decamers enhances the redox polarity of the cytosol: as vsup approaches V, reduced decamers are preferentially retained far from H2O2 sources, attenuating the local H2O2 buildup. Substantial total protein concentration gradients of both peroxiredoxins emerge under these conditions, and the concentration of reduced peroxiredoxin 1 far from the H2O2 sources even increases with vsup. Altogether, the properties of 2-Cys peroxiredoxins and thioredoxin are such that localized H2O2 supply induces a redox and functional polarization between source-proximal regions (redox microdomains) that facilitate peroxiredoxin-mediated signaling and distal regions that maximize antioxidant protection.

Kinetic and structural assessment of the reduction of human 2-Cys peroxiredoxins by thioredoxins.

We have studied the reduction reactions of two cytosolic human peroxiredoxins (Prx) in their disulfide form by three thioredoxins (Trx; two human and one bacterial), with the aim of better understanding the rate and mechanism of those reactions, and their relevance in the context of the catalytic cycle of Prx. We have developed a new methodology based on stopped-flow and intrinsic fluorescence to study the bimolecular reactions, and found rate constants in the range of 105 -106 m-1 s-1 in all cases, showing that there is no marked kinetic preference for the expected Trx partner. By combining experimental findings and molecular dynamics studies, we found that the reactivity of the nucleophilic cysteine (CN ) in the Trx is greatly affected by the formation of the Prx-Trx complex. The protein-protein interaction forces the CN thiolate into an unfavorable hydrophobic microenvironment that reduces its hydration and results in a remarkable acceleration of the thiol-disulfide exchange reactions by more than three orders of magnitude and also produces a measurable shift in the pKa of the CN . This mechanism of activation of the thiol disulfide exchange may help understand the reduction of Prx by alternative reductants involved in redox signaling.

Synthesis, characterization, DFT, biological activity evaluation, and molecular docking analysis of new 8-[(2-hydroxynaphthalen-1-yl)diazenyl]naphthalene-1,3-disulfonic acid based complexes

Three novel metal complexes of 2‑hydroxy-1-naphthaldehyde azine (HNANSA) with iron(III), nickel(II), and copper(II) have been synthesized and characterized. Various analytical methods, such as elemental analysis, infrared spectroscopy, mass spectrometry, ultraviolet–visible spectroscopy, conductivity, magnetic testing, and thermal analysis, have been used to determine the structural and physical properties of the HNANSA and its metal complexes. The results indicated that; the HNANSA acts as a monobasic bi-dentate NO donor ligand and that the metal complexes contain water molecules in different patterns. Also, density functional theory (DFT) calculations have been performed to confirm the molecular structures and to study the quantum chemical parameters of the HNANSA and its metal complexes. Furthermore, the antibacterial, antifungal, anti-inflammatory, and antioxidant activities of the HNANSA and its metal complexes have been in vitro evaluated. The findings revealed that; the metal complexes have higher bioactivty than the free HNANSA ligand. Furthermore, molecular docking analyses have been performed against 2VF5 (Escherichia coli), 3CKU (Aspergillus flavus), 5IKT (Human Cyclooxygenase-2), and 5IJT (human peroxiredoxin 2), to estimate the binding affinities and interactions of the HNANSA and its metal complexes with target proteins. The results suggest that the HNANSA and its metal complexes may have potential applications in the development of new therapeutic agents.

Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants.

In the present study, we used benzimidazolone as a starting material to efficiently synthesize several hybrid compounds of pyrazole benzimidazolone derivatives by the 1,3-dipolar cycloaddition reaction. These compounds were obtained in average yields and were characterized by NMR (1H and 13C) and HRMS analysis. The antioxidant activity of the synthesized compounds 5(a-c) and 6(a-c) was evaluated using in vitro reduction assays, including ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC). The results indicated that products 5c, 6b, and 6c exhibit higher antioxidant activity compared to the reference compounds and showed a remarkable ability to effectively remove the radical at IC50 (14.00 ± 0.14, 12.47± 0.02, and 12.82 ± 0.10 µM, respectively) under the TAC assessment. Conversely, compound 6c showed excellent activity at IC50 (68.97 ± 0.26 µM) in the FRAP assay. We carried out molecular docking and dynamics simulations to investigate the binding mode and stability of 5c, 6b, and 6c in the active site of human Peroxiredoxin 5. An ADMET study was conducted to determine the drug properties of the synthesized compounds.

Exploring the Antioxidant Potency of New Naphthalene-Based Chalcone Derivatives: Design, Synthesis, Antioxidant Evaluation, Docking Study, DFT Calculations.

Naphthalene-based chalcone derivative was successfully synthesized through the condensation of 2,4-dichlorobenzaldehyde with 2-acetylnaphthalene. This chalcone, denoted as compound 1, demonstrated a versatile reactivity upon treatment with both nitrogen and carbon nucleophiles, and yielded diverse heterocyclic scaffolds such as pyrazoline, thiazole, pyrimidine, pyran, and pyridine derivatives. The pyrazoline aldehyde derivative 7 was further derivatized to produce the hydrazide-hydrazone 13, namely, (1H-pyrazol-1-yl)methylene)acetohydrazide, which was exploited to synthesize derivatives of 2-oxo-2H-chromene-3-carbohydrazide 14, 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetohydrazide 15, and 3-(4-nitrophenyl)acrylohydrazide 16. All the newly synthesized compounds were characterized by melting point, elemental analysis, as well as FT-IR, 1 H-NMR and mass spectroscopy. Furthermore, these heterocyclic derivatives were screened for their antioxidant capacities using the DPPH radical assay. The results showed that compounds 5 and 10 are the most potent antioxidants with IC50 values 178, 177(μM), respectively. comparable to that of ascorbic acid which has IC50 value 148. Meanwhile, compounds 2, 12, 13, 14, 15, and 16 exhibited moderate antioxidant activities with IC50 values ranged from 266 to 291(μM). Thus, these heterocycles could emerge as promising antioxidant drugs for the treatment of oxidative stress-related diseases. Finally, molecular docking was conducted to study the binding affinity for the most potent antioxidant compounds 5, 10, and ascorbic acid inside the active pocket of Human Peroxiredoxin 5 (1HD2). DFT calculations and global descriptors were calculated for the most potent compounds to correlate the relation between chemical structure and reactivity.

Investigation of the Molecular Mechanisms of Mitochondrial Import and Maturation of Human Peroxiredoxins Prdx3 and Prdx5

Investigation of the Molecular Mechanisms of Mitochondrial Import and Maturation of Human Peroxiredoxins Prdx3 and Prdx5