Molecules最新文献

Obtaining water-soluble palladium complexes capable of interacting with DNA is an important synthetic task in medicinal chemistry. The interaction of [Pd(phen)(OAc)₂] (phen = 1,10-phenanthroline) with pivalic acid (^tBuCOOH) and trifluoromethanesulfonic acid (HOTf) leads to the formation of the molecular complex [Pd(phen)(OOC^tBu)₂] (1) and the ionic complex [Pd(phen)(H₂O)₂]Otf₂ (2), respectively. Complex 1 is highly soluble in water and stable in solution for 48 h. When complex 2 is boiled in water, it undergoes hydrolysis to form the binuclear hydroxo-bridged complex [Pd₂(phen)₂(μ-OH)₂]Otf₂ (3). According to X-ray diffraction data, the crystal lattices of 1-3 are stabilized by numerous intermolecular hydrogen bonds and π-π stacking interactions. The interaction of 1 and 2 with DNA in vitro (in 0.005 M NaCl solution) was studied using UV spectroscopy, low-gradient viscometry, and DNA melting analysis. It was shown that both compounds interact with DNA, and the binding is accompanied by the intercalation of the phenanthroline ligand at low concentrations in the DNA solution. An increase in their concentration leads to an alternative binding mode-palladium-DNA interaction causes a decrease in the DNA molecular coil size due to electrostatic interaction and/or palladium coordination to DNA bases. The difference between the binding of compounds 1 and 2 to DNA is that 2 can coordinate to N-bases, unlike complex 1. The antibacterial properties of the complexes have been studied in vitro against E. coli, P. aeruginosa, and S. aureus.

New diarylheptene polyphenols with α-glucosidase inhibitory activity were previously isolated and reported from the aquatic plant Ottelia acuminata var. acuminata. It was used as the template in the present research, and a series of 1,3-bisbenzylphenylphenolic compounds were designed and synthesized. The tyrosinase, α-glucosidase inhibitory effects, antioxidant properties, and whitening effects of these compounds were investigated. Of them, the representative compounds 1 and 2 inhibited the two target enzymes (tyrosinase and α-glucosidase) engaged in skin whitening and aging with comparable IC₅₀ values to the reference drugs as well as antioxidant activities. They showed potent whitening efficacy in zebrafish. In particular, compound 1 had whitening-effect rates of 31% at a concentration of 0.0001% (m/m), and 52% at a concentration of 0.0002% (m/m). Both compounds had more superior whitening efficacy than the commercially available whitening agent phenylethylresorcinol (377), which was used as a positive control. Compounds 1 and 2 did not show any genotoxicity and skin phototoxicity at the test concentrations, and they show promise as new skin-whitening agents.

Trichilia dregeana has a rich phytochemical diversity and biological activity; however, information on its metabolomic profile and antimycotoxigenic potential is limited. This study investigated different extracts of T. dregeana bark obtained with various solvents (water, ethanol, ethyl acetate, and methanol), assessing their chemical composition using LC-MS and their inhibitory activity against the aflatoxin produced by Aspergillus fungi. LC-MS analysis identified metabolites belonging to several secondary metabolite classes, including flavonoids, phenolic acids, lignan glycosides, cardiac glycosides, coumarins, cinnamic acids, and limonoids. Solvent polarity strongly influenced metabolite distribution, with water and methanol enriching polar antioxidant compounds, while ethanol and ethyl acetate extracted semipolar antimicrobial constituents. The antimycotoxigenic efficacy of T. dregeana bark extracts was evaluated against Aspergillus flavus in maize, rice, and flour matrices. Among the tested extracts, only the methanolic extract exhibited a statistically significant reduction in aflatoxin levels (µg/kg), while the water, ethanol, and ethyl acetate extracts showed no significant inhibition. Fungal inoculation significantly increased aflatoxin levels, with maize showing the highest contamination (673.32 µg/kg). At 50 µg/mL extract, aflatoxin concentrations were reduced to 230.39 µg/kg maize, 129.93 µg/kg rice, and 143.89 µg/kg flour, with efficacy comparable to or exceeding the commercial fungicide tenazole. Associations between solvent-dependent metabolite class distribution and aflatoxin suppression were observed; however, bioactivity was demonstrated exclusively at the crude extract level. These findings suggest that methanolic extracts of T. dregeana bark may represent a promising natural alternative to antimycotoxin agents, warranting further fractionation and mechanistic validation.

Background: Glioblastoma Multiforme (GBM) is one of the most aggressive primary brain tumors, with a median survival of only 15-17 months. Treatment failure is largely driven by the Blood-Brain Barrier (BBB), which restricts the delivery of most conventional therapeutics and shields invasive tumor regions from systemic drugs.

Approach: This review highlights recent advances in inorganic nanoparticles designed to cross the BBB and target GBM. These platforms, including silica-, metal-, and carbon-based nanomaterials, enable multimodal applications such as tumor imaging, localized hyperthermia, and selective induction of cancer cell death. Functionalization with targeting ligands or surface modifications further enhances tumor penetration and therapeutic efficacy.

Outlook: Despite promising preclinical results, clinical translation requires careful optimization of nanoparticle properties to minimize toxicity and immune clearance. Understanding these challenges provides a roadmap for the development of more effective nanomedicine strategies aimed at improving outcomes for GBM patients.

Arapaima gigas growth hormone (ag-GH) cDNA was previously cloned from A. gigas pituitaries. In this work ag-GH has been synthesized using human embryonic kidney 293 cells (HEK293) transiently transfected with the 3.4-TOPO^® vector carrying ag-GH cDNA. The 4th day after transfection, the presence of putative ag-GH was detected via SDS-PAGE and Western blotting in comparison with human GH. Ion exchange purification exhibited a clearly symmetric peak, absent in the control medium. The purified fraction, submitted to high-performance size-exclusion chromatography (HPSEC), SDS-PAGE, and Western blotting, contained an immunoreactive molecule, slightly smaller than hGH as expected. MALDI-TOF-MS determined a high-resolution molecular mass of 21,220 Da versus a theoretical value of 21,150. A phylogenetic analysis positioned ag-GH within basal teleost lineages, consistent with earlier analyses of A. gigas gonadotrophic hormones, reinforcing the structural and functional conservation relevant for its biologic activity. An in vivo bioassay based on the body weight increase of dwarf "little" mice demonstrated a biological activity for ag-GH comparable to that of the international reference preparation of rec-hGH. For two species (H. sapiens and A. gigas) separated by an evolutionary period of >100 million years, such a positive biological correlation is remarkable.

Understanding the competitive adsorption mechanism is crucial for the rational design of CO₂ adsorbents. In this work, the surface of zeolite 5A was modified with varying concentrations of n-octadecylphosphonic acid (ODPA) to enhance the adsorptive separation of CO₂ over C₃H₆. With a 0.01 mol/L concentration of ODPA, the modified zeolite 5A achieves CO₂/C₃H₆ ideal selectivity over 73 at 298 K, a substantial improvement over the pristine zeolite 5A, which exhibits a selectivity of 6.07. The Sips isotherm model provides an excellent fit to the experimental data, offering insights into the adsorption mechanism, with a calculated enthalpy change of -30.70 kJ/mol for CO₂ and -16.54 kJ/mol for C₃H₆, along with favorable Gibbs free energy changes ranging from -9.00 to -3.54 kJ/mol for CO₂ and -4.96 to -2.04 kJ/mol for C₃H₆ over the temperature range of 298-373 K. Kinetic analysis reveals faster diffusion in pristine zeolite 5A; however, surface modification significantly enhances CO₂/C₃H₆ selectivity while maintaining balanced adsorption capacity. Adsorption uptakes of CO₂ and C₃H₆ in pristine zeolite 5A follow the pseudo-first-order model and pseudo-second-order model, respectively. Pristine zeolite 5A shows rapid adsorption, with a CO₂ adsorption capacity of 4.10 mmol/g with a rate constant of 2.60 min^-1, and a C₃H₆ adsorption capacity of 1.99 mmol/g with a rate constant of 0.34 min^-1. The modification with ODPA increases adsorption energy barriers, with CO₂ activation energy reaching 5.18 kJ/mol and C₃H₆ activation energy up to 15.63 kJ/mol, while tetrahydrofuran washing restores site accessibility, demonstrating tunable diffusion and adsorption behavior. These findings lay the foundation for designing high-efficiency, and selective adsorbents through targeted surface engineering.

Chestnut shells are widely recognized as a source of bioactive compounds, including polyphenols and other antioxidant molecules. The industrial chestnut food chain generates large amounts of this by-product, which represents both a waste disposal challenge and a potential source of promising biomolecules. Thermal treatments occurring during industrial processing, however, may affect both chemical composition and bioactivity. Characterization of the chemical composition and biological activity of chestnut shells can contribute to the valorisation of this industrial by-product. Understanding which molecular alterations are caused by the processing is essential to assess the real potential of chestnut shell biomass. This study provides a comparative analysis of Castanea sativa shells, both raw and industrially processed. Evaluation was performed at different levels, exploiting mass spectrometry-based metabolite profiling, Total Phenolic Index analysis, antioxidant capacity, and inhibitory activity against AKR1B and AKR1B10, two reductases involved in key physiopathologic pathways. A comparison between extraction solvents (water and ethanol) and processing status (raw versus industrially processed) was performed. Overall, our results support the view that chestnut shell residues represent a valuable source of bioactive extracts. In a circular economy framework, such extracts could be developed to act on AKR1B1/AKR1B10 activity and oxidative stress, thereby contributing to the valorisation of chestnut processing by-products.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with limited therapeutic options and poor clinical outcomes. Mounting evidence suggests that targeting cancer-specific metabolic and redox adaptations represents a promising therapeutic strategy. Peroxiredoxin 1 (PRDX1), a key antioxidant enzyme that is frequently overexpressed in HCC, enables tumor cells to neutralize excessive reactive oxygen species (ROS), thereby sustaining survival and conferring therapeutic resistance. In this study, using human hepatocellular carcinoma HepG2 cells as an in vitro model, we identify ginsenoside Rg5 (Rg5) as a previously unrecognized small-molecule inhibitor of PRDX1. Structural and functional analyses demonstrate that Rg5 directly binds to the Asn145 residue of PRDX1, effectively suppressing its peroxidase activity. Mechanistically, this inhibition disrupts ROS detoxification in HepG2 cells, leading to mitochondrial ROS accumulation, activation of the intrinsic apoptotic pathway, and consequent HepG2 cell death. Additionally, Rg5 not only suppresses HepG2 cell survival but also acts synergistically with doxorubicin, a first-line chemotherapeutic agent, to markedly enhance antitumor efficacy and potentially mitigate chemoresistance. Collectively, these findings suggest that PRDX1 inhibition may represent a broadly exploitable vulnerability in liver cancer and establish Rg5 as a promising candidate for developing targeted and combinatorial therapies against HCC.

The unfolded protein response (UPR) is a highly conserved adaptive mechanism that restores endoplasmic reticulum (ER) homeostasis under stress. Beyond its canonical roles in proteostasis, the UPR has emerged as a central regulator of immune responses across diverse contexts, including infection, inflammation, cancer, and autoimmunity. IRE1α, PERK, and ATF6 are three principal UPR sensors that coordinate complex signaling networks to regulate antigen presentation, cytokine production, and immune cell differentiation. This review highlights the molecular mechanisms by which small molecules target the UPR to modulate immune responses. In addition, we highlight stress granules (SGs) and the prevalence of protein-protein interactions mediated by intrinsically low-complexity domains (LCDs) in the UPR as potential new avenues for immune modulation. Finally, we discuss future directions for leveraging UPR modulation in immunotherapy, infectious disease, and chronic inflammatory disorders.

For Co-N-C materials prepared under high-temperature calcination conditions, the formation of Co nanoparticles occurs when the metal loading exceeds 2%. Typically, CoNx is regarded as the primary active site of the catalyst, while Co nanoparticles are considered to possess limited catalytic activity. Consequently, within Co-N-C materials, Co nanoparticles are often likened to 'ballast stone' in a catalyst. In the model reaction of formic acid dehydrogenation, we incorporated boron into the precursor, thereby enhancing the electronic metal-support interactions (EMSI) between Co nanoparticles and carbon carriers. Consequently, this modification resulted in a catalytic performance of Co nanoparticles that was comparable to that of Co single-atom catalysts (SACs).