Search Results (315)

Recent studies have increasingly focused on molecular interactions between small molecules and proteins, especially binding mechanisms and thermodynamics, using multispectroscopic and molecular dynamics approaches. This study elucidated the molecular interaction mechanism between bovine serum albumin (BSA) and trans-resveratrol (Res) through an integrated approach combining multispectroscopic analyses and molecular dynamics simulations. The fluorescence quenching study revealed a static quenching mechanism between BSA and Res, which was further confirmed via ultraviolet–visible (UV-Vis) absorption spectroscopy. In particular, K_SV decreased from 5.01 × 10⁴ M⁻¹ at 298 K to 3.99 × 10⁴ M⁻¹ at 318 K. Furthermore, the calculated K_q values significantly exceeded 1 × 10¹² M⁻¹ s⁻¹. With increasing Res concentration, the peak fluorescence intensities of Tyr and Trp residues both exhibited a blue shift. The α-helix content of the BSA–Res complex was 59.8%, slightly lower than that of BSA (61.3%). Res was found to bind to site I in subdomain IIA of BSA. The molecular dynamics simulation also identified the specific binding of Res to site I of BSA, while thermodynamic studies revealed that the binding process occurs spontaneously and is primarily mediated by hydrogen bonding interactions. These findings not only enrich the theoretical framework of small-molecule–protein interactions but also provide a crucial scientific foundation for the development and utilization of natural products. Full article

Early diagnosis of Alzheimer’s disease (AD) is essential for effective treatment; however current diagnostic methods are often complex, costly, and unsuitable for point-of-care testing. Graphene-based biosensors offer an alternative due to their affordability, versatility, and high conductivity. However, graphene’s conductivity can be compromised when its carbon lattice is oxidized to introduce functional groups for biomolecule immobilization. This study addresses this challenge by developing an electrochemical immunosensor using carboxyl-modified commercial graphene foam (COOH-GF) electrodes. The conductivity of graphene is preserved by enabling efficient COOH modification through π–π non-covalent interactions, while antibody immobilization is optimized via EDC-NHS carbodiimide chemistry. The immunosensor detects tau-441, an AD biomarker, using differential pulse voltammetry (DPV), achieving a detection range of 1 fM–1 nM, with a limit of detection (LOD) of 0.14 fM both in PBS and human serum. It demonstrates high selectivity against other AD-related proteins, including tau-217, tau-181, amyloid beta (Aβ_1-40 and Aβ_1-42), and 1% BSA. These findings underscore its potential as a highly sensitive, cost-effective tool for early AD diagnosis. Full article

Background/Objectives: Understanding the molecular interactions between small bioactive compounds and serum albumins is essential for drug development and pharmacokinetics. Noraucuparin, a biphenyl-type phytoalexin with promising pharmacological properties, has shown a strong binding affinity to bovine serum albumin (BSA), a model protein for drug transport. This study aims to elucidate the structural and energetic characteristics of the noraucuparin–BSA complex under physiological and slightly elevated temperatures. Methods: Microsecond-scale molecular dynamics (MD) simulations and Molecular Mechanics Generalized Born Surface Area (MMGBSA)-binding-free energy calculations were performed to investigate the interaction between noraucuparin and BSA at 298 K and 310 K. Conformational flexibility and per-residue energy decomposition analyses were conducted, along with interaction network mapping to assess ligand-induced rearrangements. Results: Noraucuparin preferentially binds to site II of BSA, near the ibuprofen-binding pocket, with stabilization driven by hydrogen bonding and hydrophobic interactions. Binding at 298 K notably increased the structural mobility of BSA, affecting its global conformational dynamics. Key residues, such as Trp213, Arg217, and Leu237, contributed significantly to complex stability, and the ligand induced localized rearrangements in the protein’s intramolecular interaction network. Conclusions: These findings offer insights into the dynamic behavior of the noraucuparin–BSA complex and enhance the understanding of serum albumin–ligand interactions, with potential implications for drug delivery systems. Full article

Coumarins are known for interacting with proteins and exhibiting diverse biological activities. This study investigates the interaction between coumarin-343 (C343) and human (HSA) and bovine (BSA) serum albumins. Fluorescence spectroscopy and theoretical simulations, including density functional theory (DFT) and molecular docking, were used to analyze the ligand–protein complex formation. The fluorescence quenching data revealed that C343 binds to both proteins, with binding constants of 2.1 × 10⁵ mol·L⁻¹ (HSA) and 6.5 × 10⁵ mol·L⁻¹ (BSA), following a 1:1 stoichiometry. Binding site markers identified drug site I (DS1), located in subdomain IIA, as the preferential binding region for both proteins. Computational results supported these findings, showing high affinity for DS1, with binding energies of −69.02 kcal·mol⁻¹ (HSA) and −67.22 kcal·mol⁻¹ (BSA). While complex formation was confirmed for both proteins, differences emerged in the induced circular dichroism (ICD) signals. HSA displayed a distinct ICD profile compared to BSA in both intensity and absorption maximum. Molecular Docking revealed that the C343 conformation differed between HSA and BSA, explaining the variation in ICD signals. These results highlight the importance of protein structure in modulating ligand interactions and spectral responses. Full article

The effect of pH and temperature on the interaction of sodium citrate-coated magnetic iron oxide nanoparticles (IONPs) with the BSA protein was studied using optical methods. The optical properties of aqueous colloids of BSA, IONPs, and BSA with IONPs were studied with pH changes in the range of 2–12 and temperature in the range of 25–85 °C. It was found that at pH 2.0, no significant changes in the optical properties were observed with increasing temperature in aqueous colloids containing a mixture of BSA with IONPs. Temperature affects the optical properties of BSA colloids with IONPs in the pH range from 5.0 to 8.0. Moreover, by increasing the temperature at these pH levels, it is possible to control the particle size in the colloids. In general, both temperature and pH have a significant effect on the properties of the aqueous colloid of BSA with IONPs and allow for the control of interactions between BSA and IONPs, namely, the processes of aggregation, particle reclustering, and protein denaturation. Full article

We report on the synthesis and characterization of a novel fluorenyl-methoxycarbonyl (Fmoc)-containing thioxo-triazole-bearing dipeptide 5, evaluated for potential therapeutic applications. The compound was tested for its antioxidant and antimicrobial properties, demonstrating significant effects in scavenging reactive oxygen species (ROS) and inhibiting microbial growth, particularly when combined with plant extracts from an endemic Peonia species from the Caucasus. Circular dichroism (CD) binding studies with bovine serum albumin (BSA) and calf thymus DNA revealed important interactions, suggesting the dipeptide’s potential in biomedically relevant conditions that involve DNA modulation. Molecular docking and CD spectra deconvolution provided additional insights into the binding mechanisms and structural characteristics of the formed complexes with the biomolecular targets. The Fmoc group enhances the dipeptide’s lipophilicity, which may facilitate its interaction with cellular membranes, supporting efficient drug delivery. A computational evaluation at the ωB97XD/aug-cc-pVDZ level of theory was carried out, confirming the experimental results and revealing a powerful potential of the peptide as an antioxidant, through FMOs, MEP analysis, and antioxidant mechanism assessments. Together, these findings suggest that this dipeptide could be valuable as an antimicrobial and antioxidant agent, with potential applications in pathologies involving oxidative stress, DNA modulation, and microbial infections. Full article

Their demonstrable bioactive characteristics, coupled with their wide structural diversity and coordination versatility, render Schiff bases and their coordination complexes biologically active compounds demonstrating outstanding properties. This research describes the synthesis and characterization of new Cu(II) and Ni(II) complexes with an NNO-donor hydrazone ligand (HL). The crystal structure of the HL ligand was determined through single-crystal X-ray diffraction studies. The in vitro antibacterial activities of the HL ligand and its metal(II) complexes against Gram-positive and Gram-negative bacteria demonstrated that the metal(II) complexes displayed greater antimicrobial activities compared to the free Schiff base ligand. Furthermore, the interaction of the ligand and the complexes with calf thymus DNA (CT-DNA) was explored through electronic absorption and viscosity measurements, suggesting intercalation as the most likely mode of binding. The compounds promoted oxidative DNA cleavage, as demonstrated by the strand breaks of the pmChery plasmid under oxidative stress conditions. Finally, fluorescence spectroscopy also revealed the strong binding affinity of these compounds for bovine serum albumin (BSA). Full article

Morin is a natural flavonoid with potent antioxidant activity, yet its clinical and nutraceutical applications remain limited due to poor aqueous solubility and low bioavailability. This study explores the interaction of morin with bovine serum albumin (BSA) and the development of BSA-based nanoparticles as a delivery platform. Fluorescence spectroscopy confirmed the formation of a stable 1:1 morin–BSA complex, governed by hydrophobic interactions, with a binding constant (Ka) of 1.87 × 10⁵ L·mol⁻¹. Binding conferred enhanced photostability, as BSA attenuated morin degradation under oxidative stress conditions. BSA nanoparticles prepared by desolvation encapsulated morin with high monodispersity and encapsulation efficiencies up to 26%. Co-encapsulation with ellagic acid or tocopherol succinate improved loading capacity but reduced morin release, suggesting intermolecular stabilization. Release studies in simulated intestinal fluid showed controlled diffusion, while compatibility assays in milk-based food matrices confirmed colloidal stability in whole and reduced-fat milk. These findings support BSA–morin nanoparticles as a promising system for the oral delivery and functional food incorporation of polyphenolic antioxidants. Full article

This study was the first to analyze the chemical compositions and bioactivities of Serissa japonica leaf oil. The oil, obtained via hydro-distillation with a 0.1% yield, contained 64 compounds, predominantly non-terpenic compounds (39.0%), oxygenated sesquiterpenes (31.4%), and oxygenated monoterpenes (25.6%). Major constituents included 1,8-cineole, (E)-nerolidol, and iso-longifolol. The oil showed good antioxidant activity (IC₅₀ ≈ 62.79 ± 0.77 µg/mL for DPPH and 57.82 ± 1.12 µg/mL for ABTS) and a good anti-tyrosinase effect (IC₅₀ ≈ 195.6 ± 3.82 µg/mL). The trend was similar to anti-inflammatory activity, with an IC₅₀ value of 63.03 ± 3.22, for NO inhibition without cytotoxicity at 100 µg/mL. The bovine serum albumin (BSA) blocking assay demonstrated an IC₅₀ value of 59.31 ± 0.71 µg/mL, indicating a good interaction regarding enzyme inhibition. Moreover, the computational modeling of the possible association between tyrosinase and cyclooxygenase-2 highlighted their antioxidant and anti-inflammatory properties. The results pointed out the usefulness of S. japonica essential oil as a natural candidate for managing oxidative stress and inflammation. Full article

Background/Objectives: Clarithromycin (CLA) is a widely used antibiotic effective against a variety of bacterial strains, making it a common treatment for respiratory, skin, and soft tissue infections. Moreover, extensive studies have confirmed the anticancer activity of CLA against different cancers, particularly when combined with conventional therapies. This study investigates the potential anticancer and antibacterial activities of developed CLA-loaded bovine serum albumin nanoparticles (CLA-BSA NPs), designed with optimized physicochemical properties to enhance drug delivery. Methods: The CLA-BSA NPs were synthesized using the desolvation method, followed by drug loading. Characterization techniques, including Dynamic Light Scattering (DLS), Fourier-Transform Infrared (FTIR) Spectroscopy, X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Thermogravimetric Analysis (TGA). Results: The results confirmed that CLA interacts with BSA NPs through van der Waals forces. The performance of drug–nanocarrier interaction was further assessed through in vitro drug release studies. The release studies demonstrated that CLA had a robust release profile in reductive media, with a cumulative release of 50.9% in acetate buffer (pH 5.0) supplemented with 10 mM glutathione (GSH). Further biological activity assays were also conducted, including cell viability assays (MTT) and antibacterial activity tests. CLA-BSA NPs demonstrated anticancer activity against the lung cancer (A549) cell line, while showing minimal cytotoxicity on normal human dermal fibroblast (HDF) cells. The antibacterial activity was assessed against Streptococcus pyogenes, Bacillus cereus, and Staphylococcus aureus. Among the tested strains, Bacillus cereus exhibited the highest sensitivity, with a minimum inhibitory concentration (MIC) of 0.032 µg/mL, compared to 0.12 µg/mL for Staphylococcus aureus and >32 µg/mL for Streptococcus pyogenes. Conclusions: In conclusion, these findings highlight CLA-BSA NPs as a promising drug delivery system that enhances the anticancer and antibacterial efficacy of CLA. Full article

Background/Objectives:Bougainvillea x buttiana is used in traditional Mexican medicine to treat various diseases. Previous studies have demonstrated its anti-inflammatory properties, which are associated with its chemical composition. This study evaluated the effect of ethanol concentration on the yield and anti-inflammatory activity of its extracts. Additionally, an in silico analysis of the plant’s previously identified phytochemicals was conducted. Methods: Four extracts of B. x buttiana (var. Rose) (labeled as BxbREE) were prepared with increasing concentrations of ethanol (0%, 50%, 80%, and 100%). Their anti-inflammatory activity was assessed using different in vitro assays. The in silico prediction, performed with SwissADME, included the physicochemical, pharmacokinetic, and drug-like properties of the compounds. Results: The findings indicated that varying the ethanol concentration in the preparations of BxbREE-0%, BxbREE-50%, BxbREE-80%, and BxbREE-100% significantly impacted the extraction yield, with BxbREE-0% and BxbREE-50% exhibiting the highest recovery. All four extracts demonstrated significant anti-inflammatory activity, with BxbREE-50% and BxbREE-80% showing the most important effects on the denaturation of bovine serum albumin (BSA) and trypsin, inhibition of pro-inflammatory enzymes (cyclooxygenase and phospholipase A2), and increased stability of the erythrocyte membrane. The in silico analysis revealed that most phytochemicals identified in the extracts had good drug-likeness and bioavailability for oral administration and an adequate ADME profile. Conclusions: These findings reaffirm the anti-inflammatory potential of B. x buttiana (var. Rose) ethanolic extracts and the favorable pharmacokinetic and pharmacodynamic properties of its phytochemicals. Further structural exploration of the interactions of these bioactive compounds could contribute to the design of new drugs. Full article

The objective of this study was to synthesize thiazoline-2-thione derivatives (1a, 2b, 3c and 4d) and examine their anti-inflammatory properties as potential alternatives to Aspirin (NSAID), which is known for its side effects, including liver damage. The study employed a multifaceted approach that integrated in vitro assays, molecular docking, ADMET predictions, molecular dynamics simulations (300 ns for each system) and detailed DFT calculations. These four molecules were initially evaluated for their effectiveness in inhibiting the denaturation of bovine serum albumin (BSA), a key indicator of their potential anti-inflammatory activity. The results show that 4d displayed notable inhibitory potential against BSA denaturation, with an IC₅₀ value of 21.9 µg/mL, outperforming the efficacy of Aspirin (22 µg/mL). In comparison, 3c exhibited an IC₅₀ value of 31.7 µg/mL. Molecular docking studies with the BSA active site revealed that 4d and 3c had the highest binding affinities, with binding energies (∆G) of −5.274 and −4.731 kcal.mol⁻¹, respectively. Aspirin showed a ∆G of −4.641 kcal.mol⁻¹. These findings suggest that 4d and 3c molecules exhibit stronger interactions with BSA, indicating superior anti-inflammatory activity compared to Aspirin. In addition, molecular dynamics simulations, cross-dynamic correlation matrix (DCCM), free energy landscape (FEL), MM-PBSA and detailed DFT calculations provided further evidence that 4d formed stable molecular interactions with the BSA receptor. These analyses highlighted the strong binding stability of 4d, indicating that it maintains consistent interactions over time. The results also suggested that 4d exhibits favorable energy profiles, good pharmacokinetic features and optimal molecular behavior within the BSA active site. Finally, the results of this study are promising for the development of new anti-inflammatory drugs, highlighting potential compounds that could offer effective and safer alternatives to existing treatments. Full article

To address the limitations of traditional endotoxin adsorbents, which exhibit poor endotoxin removal efficiency and low sample recovery when processing high-concentration samples, a novel cryogel, CG(HEMA-co-AM), based on acrylamide (AM) and hydroxyethyl methacrylate (HEMA) as the second monomer, was successfully designed and synthesized. After optimizing the epoxidation and polymyxin B (PMB) conjugation processes, leading to the successful preparation of the functionalized cryogel CG(HEMA-co-AM)@ECH@PMB, flow-through experiments showed that in Tris-HCl buffer at a flow rate of 6 mL/min, the endotoxin removal efficiency reached 99.82%, with a maximum adsorption capacity of 1408.38 EU/mg. In a complex protein system containing BSA, HSA, Hb, LYS, and OVA (each at 10 mg/mL), the maximum endotoxin removal efficiency was 99.62%. Further investigations revealed that pH and ionic strength critically influenced the regulation of hydrophobic and electrostatic interactions, thus significantly affecting the endotoxin adsorption efficiency. Additionally, weakly hydrophobic and basic lysozyme exhibited significantly higher recovery rates compared to strongly hydrophobic and acidic proteins such as BSA and OVA. This functionalized cryogel integrates a high adsorption capacity with excellent specificity and features a macroporous structure suitable for dynamic chromatographic separation. It offers a novel, reusable adsorbent material for endotoxin removal in protein preparation, biopharmaceutical production, and clinical blood purification applications. Full article

Precise separation and antifouling capabilities are critical for the application of membrane separation technology. In this work, we developed a multiplayer layer-by-layer assembly strategy to sequentially deposit tannic acid (TA) and lysozyme (Lys) onto polyethersulfone/iron (PES/Fe) ultrafiltration membrane substrates, enabling the simple and efficient fabrication of a biofouling-resistant loose nanofiltration (LNF) membrane with superior dye/salt separation performance. This approach fully leverages the multifunctionality of TA by exploiting its coordination with Fe³⁺ and non-covalent interactions with Lys. The obtained PES/Fe-TA-Lys LNF membrane exhibits a pure water flux of 57.5 L·m⁻²·h⁻¹, along with exceptional dye rejection rates (98.3% for Congo Red (CR), 99.2% for Methyl Blue (MB), 98.4% for Eriochrome Black T (EBT), and 67.6% for Acid Orange 74 (AO74)) while maintaining minimal salt retention (8.2% for Na₂SO₄, 4.3% for MgSO₄, 3.5% for NaCl, and 2.4% for MgCl₂). The PES/Fe-TA-Lys LNF membrane also displays outstanding antifouling performance against bovine serum albumin (BSA), humic acid (HA), and CR, along with strong biofouling resistance against Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) via synergistic anti-adhesion and biofilm inhibiting effects. This work presents a novel and scalable approach to fabricating biofouling-resistant LNF membranes, offering great potential for dye/salt separation in textile wastewater treatment. Full article

Objectives: This study aimed to develop and evaluate nanostructured lipid carriers (NLCs) loaded with meloxicam (Melox) and a therapeutic antibacterial and anti-inflammatory liquid lipid, clove oil (CO) for periodontitis treatment, a complex inflammatory condition necessitating advanced drug delivery systems. The NLC–Melox formulation was integrated into three hydrogels, hypromellose (HPMC), zinc hyaluronate (ZnHA), and sodium hyaluronate (NaHA), to conduct a comparative analysis focusing on enhanced localized drug delivery, improved mucoadhesion, prolonged retention, and significant therapeutic outcomes. Methods: NLC–Melox was prepared by homogenization and characterized by dynamic light scattering (DLS). Subsequently, NLC–Melox-loaded gels were subjected to transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Raman spectroscopy, and rheological analysis. In vitro drug release, anti-inflammatory activity (BSA denaturation assay), and antibacterial efficacy (MIC, MBC) were investigated to assess therapeutic potential. Results: DLS revealed a particle size of 183 nm with a polydispersity index of 0.26, indicating homogeneity. TEM confirmed consistent morphology and uniform nanoparticle distribution. DSC and XRD demonstrated the amorphous nature of Melox, enhancing solubility and stability. Spectroscopy confirmed no chemical interactions between components. Rheological studies identified ZnHA as the most mucoadhesive and structurally stable gel. In vitro release studies showed sustained drug release over 24 h. Melox and CO-loaded formulations demonstrated significant anti-inflammatory activity and notable antibacterial efficacy due to the antibacterial oil. Conclusions: The study highlighted the potential of NLC-based mucoadhesive hydrogels as an effective strategy for periodontitis treatment. The formulation offered improved drug solubility, therapeutic efficacy, mucoadhesivity, and prolonged delivery, making it a promising candidate for localized therapy. Full article