Bioinorganic Chemistry and Applications最新文献

The oxidative stress of the body can destroy the homeostasis and lead to a series of adverse outcomes. In recent years, nano-enzyme materials, as a new hotspot in materials science, have been gradually applied in various fields because of their enzyme-like activities at the nanoscale and their ability to regulate various physiological processes in organisms. In this study, we developed a novel cerium oxide (CeO₂) nano-enzyme drug and demonstrated that the nano-enzyme can effectively improve oxidative stress levels and delay disc degeneration in rats. The experimental results confirmed that in in vitro experiments, the novel cerium oxide nano-enzyme could significantly reduce the ROS level in cells, delay cell senescence, reduce the level of apoptosis, and improve the metabolic state of nucleus pulposus cells. At the same time, it maintains low toxicity to cells. At the animal level, imaging and histomorphological evaluation showed that the novel cerium oxide nano-enzyme could significantly improve the disc height index, MRI Pfirrmann grade, and histological grade scores in rats. In summary, we have developed a successful cerium oxide nano-enzyme, which can be used to reduce the degeneration level of intervertebral disc and provide a new potential idea for clinical treatment of patients with lumbar disc herniation.

Research into the use of nanoparticles to enhance the delivery and efficacy of polyphenols is a topic of growing interest in the fields of nanotechnology, pharmacology and food science. Nanoparticles, due to their small size and high surface area, can improve the stability, solubility and bioavailability of polyphenols. Combining polyphenols with other bioactive compounds within nanoparticles can create synergistic effects, enhancing their overall therapeutic potential. In this work, we present a new polyethylene glycol (PEG) capping ligand modified with caffeic acid (CA), HS-PEG-CA and two types of gold nanoparticles: (i) coated with a PEG-thiol derivative functionalized with CA (HS-PEG-CA) (homofuncionalized NP) and (ii) HS-PEG-CA cationic carbosilane dendrons with antibacterial properties (heterofuncionalized NP). The antioxidant capacity of the CA, in three systems, has been studied by different techniques such as FRAP, DDPH and cyclic voltammetry, demonstrating that it is preserved when it is supported on the NP and increases when it is part of the PEG ligand. In addition, heterofuntionalized NP showed activity against S. aureus and HS-PEG2K-CA ligand can effectively anchor to gold substrates.

Alzheimer's disease (AD) is the most common neurodegenerative disorder associated with cognitive decline and loss of memory. It is postulated that the generation of reactive oxygen species (ROS) in Fenton-like reaction connected with Cu(II)/Cu(I) redox cycling of the Cu(II)-aβ complex can play a key role in the molecular mechanism of neurotoxicity in AD. Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic regulatory peptide that possesses a high affinity for Cu(II) ions. The ability of the peptide Semax to inhibit the copper-catalyzed oxidation of aβ was studied in vitro and discussed. The results indicate that Semax is able to extract Cu(II) from Cu(II)-aβ species as well as to influence the redox cycling of the Cu(II)-aβ complex and decrease the level of associated ROS production. Finally, our data suggest that Semax shows cytoprotective properties for SH-SY5Y cells against oxidative stress induced by copper-catalyzed oxidation of the aβ peptide. This study provides valuable insights into the potential role of Semax in neurodegenerative disorders and into the design of new compounds with therapeutic potential for AD.

In recent years, the development of multinuclear platinum complexes has introduced a new era in platinum-based chemotherapy, offering improved cytotoxicity and the ability to overcome resistance. However, these complexes still face challenges related to water solubility, biodistribution, and targeted delivery. This study provides a comprehensive investigation of a novel platinum (II) complex, [Pt₂(μ-bpy-2H) (Me)₂(dmso)₂] (C1), focusing on its DNA binding ability and anticancer activity. Computational and experimental approaches revealed that C1 binding to guanine bases and involvement of intercalative interactions. C1 exhibited cytotoxicity in both cisplatin sensitive and resistant cancer cell lines. To enhance the pharmacokinetic and pharmacodynamic properties of C1, it was encapsulated using poly (D, L-lactic-co-glycolic acid) (PLGA). Molecular dynamic simulations predicted the formation of stable C1/PLGA complexes during the early stages of simulation. Encapsulated C1 showed superior antitumor activity with significantly reduced side effects in tumor-bearing mouse models. In conclusion, this study highlights the novel platinum (II) complex C1 as a promising anticancer agent, especially when paired with PLGA encapsulation to improve its effectiveness and reduce side effects.

This study investigated the cytotoxic properties of three naphthyl-substituted ruthenium(II)-arene complexes (Ru1, Ru2, and Ru3) against various cancer cell lines (MCF-7, Caco-2, and HepG2) and a healthy cell line (Vero). Herein, we report the novel synthesis and characterization of Ru3 for the first time. The complexes were fully characterized by ¹H, ¹³C, and 2D NMR spectroscopies, and their interactions with DNA and bovine serum albumin (BSA) were evaluated. Binding constant (Kb) determinations revealed values of 2.95 × 10⁴ M^-1, 2.27 × 10⁴ M^-1, and 3.70 × 10⁴ M^-1 for Ru1, Ru2, and Ru3 with FS-DNA, respectively, while Ru2 exhibited a significantly higher binding constant of 0.86 × 10⁵ M^-1 with BSA, indicating a favorable binding interaction. Molecular docking of Ru3 was performed against BSA, EGFR wild type (EGFRWT), and mutant EGFRT790M. Ru3 exhibited docking scores of -178.827, -204.437, and -176.946 kJ/mol with BSA, EGFRWT, and EGFRT790M, respectively. Cytotoxicity assays revealed that Ru1-3 exhibited superior activity against MCF-7 and Caco-2 cells compared to HepG2 cells. Following a 24-h exposure, Ru2 exhibited an IC₅₀ of 1.39 μg/mL against the Caco-2 cell line. Morphological analysis suggested that all complexes induced apoptosis in cancer cells. Notably, Ru2 demonstrated minimal activity against Vero cells, indicating selectivity. Hirshfeld surface analysis was employed to investigate intermolecular interactions within the crystal structures of the complexes, providing insights into their molecular shapes and potential for interactions with other molecules. In conclusion, this study highlights the promising potential of naphthyl-substituted ruthenium(II) complexes as anticancer agents. Their selective cytotoxicity and ability to induce apoptosis warrant further investigation for the development of novel cancer therapies.

Bioactive molecule-based synthesis of silver nanoparticles (AgNPs) offers an eco-friendly approach with high therapeutic potential; however, research in this area remains limited. This study introduces hot melt extrusion (HME) technology to enhance the extraction efficiency of bioactive compounds, including astaxanthin, from the microalgae Haematococcus pluvialis (Hp). AgNPs were synthesized using HME-processed Hp (H-Hp/AgNPs), confirmed by a color change and UV-vis absorption spectrum. The resulting H-Hp/AgNPs exhibited an average size of 129.7 ± 10.4 nm, a polydispersity index of 0.2 ± 0.3, and a zeta potential of -31.54 ± 0.2 mV, indicating high stability. The synthesized AgNPs demonstrated antibacterial activity by inhibiting the growth and biofilm formation of antibiotic-resistant bacteria. Cell viability assays revealed that normal cells maintained over 100% viability at most concentrations of H-Hp/AgNPs, while cancer cells exhibited significant cytotoxicity (34.1 ± 3.1%) at 250 μg/mL. Furthermore, H-Hp/AgNPs induced apoptosis in MDA-MB 231 cells, as evidenced by mitochondrial membrane potential loss, nuclear condensation, and apoptosis, confirmed through AO/EB, Rh123, and PI staining. Additionally, H-Hp/AgNPs showed no hemolytic activity at concentrations below 250 μg/mL, ensuring safety. In conclusion, this study highlights the potential of biosynthesized H-Hp/AgNPs as promising candidates with antioxidant, antibacterial, biocompatibility, and anticancer properties.

In this study, a tetradentate 1,3-propanediamine-N,N'-diacetate (1,3-pdda^2-) was utilized for the synthesis of a dinuclear gallium(III) complex, uns-cis-[Ga(1,3-pdda)(µ-OH)]₂ ^.2H₂O (1). Complex 1 was characterized using IR and NMR (¹H and ¹³C) spectroscopy, and its crystal structure was determined by single-crystal X-ray diffraction analysis. Both Ga(III) ions in Complex 1 exhibit octahedral geometry, with each ion coordinated by two nitrogen and two oxygen atoms from the 1,3-pdda^2- ligand, as well as two oxygen atoms from the bridging hydroxyl groups. IR and NMR (¹H and ¹³C) spectra were simulated using DFT methods, showing a high degree of correlation with experimental data. Hirshfeld surface analysis provided insights into intermolecular interactions, with H⋯O and H⋯H interactions contributing significantly to the crystal stability. The antimicrobial potential of Complex 1 was evaluated alongside previously synthesized gallium(III) complexes, Na[Ga(1,3-pdta)]·3H₂O (2) and Ba[Ga(1,3-pndta)]₂·3H₂O (3), with 1,3-pdta^4- (1,3-propanediamine-N,N,N',N'-tetraacetate) and 1,3-pndta^4- ((±)-1,3-pentanediamine-N,N,N',N'-tetraacetate), respectively. Among all the tested microbial species, the gallium(III) complexes have shown selective activity against Pseudomonas aeruginosa PAO1 strain and were able to reduce pyocyanin production by 40-43% in the clinical isolate BK25H of this bacterium. Moreover, Complexes 1-3 can modulate the quinolone-mediated quorum sensing system in P. aeruginosa PAO1. Interaction studies with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) were conducted to evaluate the binding affinity and mode of interaction of Complex 1 with key biomolecules, aiming to assess its potential for transport via serum proteins and its safety profile in terms of DNA interactions. Spectrofluorimetric experiments and molecular docking revealed that Complex 1 binds strongly to the Site I on BSA, with weaker interactions at the Site II. While spectrofluorimetric studies showed that Complex 1 has a slight affinity for minor groove binding or intercalation to ct-DNA, docking studies suggested some minor groove binding, especially in larger DNA sequences, with enhanced stabilization in 10-bp-DNA through hydrogen and carbon bonds.

Five new Schiff bases from 4-aminoantipyrine were synthesized, characterized, and evaluated for their antimicrobial and DNA cleavage activities, and drug similarity properties and cytotoxicity prediction using in silico analysis. All Schiff bases had good antibacterial and antifungal activities. All compounds showed self-activating DNA cleavage ability in the absence of any reductant or oxidant at low concentrations. Modified carbon paste electrodes were prepared with all Schiff bases, and a glucose biosensor was designed. Schiff base coded (4AA-Fc) was found to have the best sensitivity to H₂O₂. It was observed that the prepared biosensor has a working range at low concentrations (1.0 × 10^-7-1.0 × 10^-6 M (R ² = 1.0)) and a low detection limit (1.0 × 10^-8 M). At the same time, 4AA-Fc was found to be a potent compound for bactericidal and fungicidal effect, killing pathogens. Thus, it could be used for the development of a resistant biosensor in external environment. It also showed a complete DNA degradation. In silico ADME analysis and cell line cytotoxicity studies found these new Schiff bases to have favorable drug-like properties, indicating potential for the development of therapeutic drugs. In particular, the compounds were not a P-gp substrate. Thus, they could be a potential anticancer agent. The present study may be useful for further scientific research in the field of the design, synthesis, and biological studies of bioactive substances.

This study describes a green synthesis method for silver nanoparticles (AgNPs) using autochthonous "Mollar de Elche" pomegranate peel extract and optimized through a Python-programmed Box-Behnken design (BBD) created specifically for the work. The bioactive compounds in pomegranate, particularly punicalagin, serve as effective reducing and stabilizing agents. BBD was used to analyze the effects of dependent variables such as silver nitrate concentration, pomegranate extract concentration, and temperature on responses such as hydrodynamic diameter, polydispersity index, and zeta potential, minimizing experimental trials and highlighting variable interactions. Optimal conditions were experimentally validated and agreed well with the predicted values. The optimized AgNPs were characterized via ultraviolet-visible spectrophotometry, Fourier transform infrared spectroscopy, X-ray diffraction, and field emission scanning electron microscopy. These AgNPs demonstrated substantial antibacterial activity against Escherichia coli and Staphylococcus aureus. Furthermore, the AgNPs were incorporated into nanofibrous scaffolds as a proof of concept for potential biomedical applications, where their antibacterial activity was partially retained postincorporation. This study highlights the potential of pomegranate extract as a sustainable medium for AgNP synthesis with promising antibacterial applications and the ability of the BBD as a useful tool for efficient optimization of multivariable processes, including the synthesis of nanomaterials.

The compelling attributes of quinoline scaffolds in medicinal compounds have garnered considerable attention from researchers, due to their notable biological efficacy, biocompatibility, and distinctive photophysical properties. Quinoline complexes, in particular, have emerged as significant entities, demonstrating a wide array of medicinal properties, including antibacterial, antifungal, antiviral, anticancer, anthelmintic, anti-HIV, antioxidant, antituberculosis, and antimalarial activities. In addition, they showed promise in photodynamic and neurological studies, along with strong DNA-binding capabilities. In recent years (2010-2023), substantial progress has been made in understanding quinoline complexes. Key aspects such as the lipophilicity, of metal complexes, enzymatic drug degradation factors influencing inhibition, drug performance, disruption of target cell growth, and their impact on DNA have been thoroughly investigated. Researchers have employed advanced methodologies including fluorescent imaging, determination of MIC and IC₅₀ values, hydrodynamic and spectrophotometric techniques, in silico and in vitro studies, and cytotoxicity assessments using the MTT method, to significantly enhance our understanding of these complexes. Recent findings indicated that the interaction of quinoline complexes with viral proteins and their ability to disrupt enzyme-viral DNA relationships have made them powerful therapeutic agents for severe diseases including cancer, AIDS, and coronaviruses, as well as various neurological and microbial infections. It is anticipated that these explorations will lead to effective advancements in therapeutic strategies within modern medicine.