BMC Chemistry最新文献

Nucleotides, such as 5’-AMP and ATP, are essential biomolecules in modern organisms. The phosphorylation of nucleosides to generate nucleotides occurs in complex prebiotic environments, where metal ions played a pivotal role, particularly in the metal-rich ancient oceans. Investigating the impact of prebiotic metal ions on nucleotide formation is critical to understanding their contributions to chemical evolution. Herein, we examined adenosine phosphorylation in the presence of various metal ions (Mn²⁺, Fe²⁺, Fe³⁺, Co²⁺, Ni²⁺, and Mg²⁺) under wet-dry cycling conditions. The results reveal that these systems can produce 5’-AMP, 2’/3’-AMP, 2’,3’-cAMP, ADP, ATP, c-di-AMP, and the oligomeric nucleotide pApA. The yields of these nucleotides varied depending on the metal ions present and were lower than in the metal-free system. The concentrations and combinations of metal ions in a solution markedly impact the levels of nucleotides. Notably, 5’-AMP emerged as the dominant product, exhibiting high 5’-regioselectivity, strongly supporting the RNA world hypothesis. Moreover, Co²⁺ and Ni²⁺ enhanced nucleotide cyclization, while iron proved crucial for oligonucleotide formation. Intriguingly, hydrolysis experiments revealed nucleotides interconversion. Furthermore, metal accelerated hydrolysis of nucleotides compared to the metal-free system, directly impacting the efficiency and final yield of nucleoside phosphorylation. These findings underscore the multifaced role of metal ions in regulating phosphorylation, facilitating hydrolysis, and promoting nucleotides interconversion, thereby advancing our understanding of prebiotic chemical evolution and providing empirical support for environments rich in metals, as plausible settings for the emergence of primordial RNA-based life.

A simple, precise, and stability-indicating reverse-phase high-performance liquid chromatography method was developed and validated for the simultaneous estimation of dapagliflozin, linagliptin, and metformin hydrochloride in fixed-dose combination tablets. Chromatographic separation was achieved using a Phenomenex Luna C18 column (250 × 4.6 mm, 5 μm) with a mobile phase consisting of acetonitrile and phosphate buffer (pH 6.8) in a 40:60 v/v ratio; the buffer was modified to the mentioned pH with triethylamine and orthophosphoric acid. The flow rate was maintained at 0.8 mL/min, with detection at 230 nm. The method demonstrated excellent linearity within the ranges of 20–140 µg/mL for metformin hydrochloride, 0.2–1.4 µg/mL for linagliptin, and 0.6–2.8 µg/mL for dapagliflozin, with correlation coefficients (R²) > 0.995. The validation was performed as per ICH Q2 (R2) guidelines, confirming the method’s accuracy, precision (%RSD < 2%), robustness, specificity, and sensitivity. Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic conditions confirmed the method’s capability to resolve each analyte from its degradation products, affirming its stability-indicating nature. Application of the method to a commercial formulation yielded assay values of 101.41%, 100.04%, and 99.73% w/w for metformin hydrochloride, linagliptin, and dapagliflozin, respectively. These results validate the method’s applicability for routine quality control and stability testing of multi-drug antidiabetic formulations.

Bilastine (BIL) is a new second-generation antihistaminic drug used for the management of urticaria and rhino-conjunctivitis symptoms. Herein, a spectrofluorimetric method for determining BIL is described. The method is very sensitive, simple, quick, and green. The suggested method depended on the measurement of the original fluorescence of BIL in 1.0 M sulfuric acid at an emission wavelength of 385 nm after an excitation at 272 nm. The method was evaluated by the International Council on Harmonization (ICH) requirements. The relationship between BIL concentrations and the fluorescence intensities was linear in a range of 10.0–500.0 ng mL^− 1, and the correlation coefficient was 0.9999. The detection limit was 2.9 ng mL^− 1 and the quantitation limit was 8.8 ng mL^− 1. The suitable sensitivity and selectivity of the suggested method enabled its application successfully in analyzing BIL in pharmaceutical tablets without any interfering effect from their excipients and in spiked human plasma with appropriate recoveries from 95.72 to 97.24%. Additionally, the suggested method was utilized for content uniformity testing.

This study aimed to synthesize new aza-acyclic nucleosides (aza-acyclovir) and evaluate the efficacy of these synthetic compounds as potential antimicrobial, anticancer, and antioxidant agents. We prepared two novel aza-acyclic nucleosides via two reactions. The first reaction involved trichloroisocyanuric acid and dibenzosulphonyl diethylamine, and the second reaction involved trichloroisocyanuric acid and diethanolamine. We then used one-dimensional nuclear magnetic resonance (NMR) spectroscopy, two-dimensional NMR spectroscopy, infrared spectroscopy, and mass spectrometry to determine the structures of the resulting compounds. In this regard, we first tested the antimicrobial activity of these compounds against various bacteria, including Bacillus cereus, B. subtilis, Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa, and against fungal pathogens, including Aspergillus fumigatus, Candida tropicalis, and Alternaria solani. Next, the precise mode for the interaction between synthesized aza-acyclic nucleosides and the target protein 8HQ5 was elucidate using molecular docking analysis. Subsequently, we tested the synthesized compounds for putative anticancer activity at different concentrations (i.e., 12.5, 25, 50, 100, and 200 µg/mL) against A549 cell (Human epithelial lung carcinoma) and human umbilical vein endothelial cell (HUVEC) lines. In addition, compounds antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl-based and cupric reducing antioxidant capacity-based methods at different concentrations (i.e., 31.25, 62.5, 125, 250, and 500 µg/mL). Results revealed that both aza-acyclic nucleosides inhibited both bacterial and fungal strains, although toxicity toward bacterial strains was generally greater than toward fungal strains. We also observed that the molecular docking results were consistent with the results of in vitro antimicrobial assessments. Further, both aza-cyclic nucleosides exhibited cytotoxic effects against both the A549 cell and HUVEC lines. Despite exhibiting lower radical scavenging activity than ascorbic acid (an antioxidant compound used as a standard), Compound 1 from the novel synthetic aza-acyclic nucleosides showed a higher reduction capacity, which was dose-dependent. Overall, we report newly synthesized compounds that show promising antimicrobial, anticancer, and antioxidant effects.

Graphical abstract

In this study, novel linear 3-(arylamino)naphtho[2,3-b]furan-2,4,9(3H)-trione derivatives has been synthesized via annulation reaction of 2-hydroxy-1,4-naphthoquinone with aromatic amines and glyoxylic acid monohydrate using p-TSOH as catalyst at ambient temperature for the first time. The mechanism proceeds via an initial intermolecular aldol condensation, subsequent Michael addition, and final intramolecular nucleophilic annulation. The linear or angular configurations of the products was confirmed through ¹-¹³ C heteronuclear multiple-bond correlation (HMBC) analysis. To evaluate the inhibitory activity of the synthesized compounds, computational methods such as molecular docking and ADME analysis were employed. Compounds 4h and 4i displayed potent activity against tested estrogen receptor alpha (ERα) as compared to Doxorubicin.

Celecoxib (CLB) and tramadol (TRD) are frequently co-administered in clinical practice due to their complementary mechanisms in managing acute and chronic pain. Their combination has recently been formulated into a fixed-dose oral medication, representing the first FDA-approved multimodal analgesic targeting COX-2 and central opioid receptors simultaneously. However, the strong spectral overlap between CLB and TRD complicates their simultaneous determination using traditional spectrophotometric methods. In this study, a chemometric-assisted spectrophotometric method was developed for the simultaneous quantification of CLB and TRD without prior separation. The classical least squares (CLS) were ultimately selected due to its suitability when pure spectra are available, its robustness with small calibration sets, and its greater interpretability for routine quality control. A five-level, two-factor experimental design produced 25 binary mixtures, split into 13 calibration and 12 validation samples. After spectral preprocessing and removal of non-informative regions, the CLS model was applied to 81 variables across the 210–290 nm range. The model achieved mean recovery values of 99.85% for CLB and 99.99% for TRD in the calibration set, and 101.29% for CLB and 99.52% for TRD in the validation set, demonstrating excellent accuracy and consistency across both datasets. Linearity was established in the range of 6–14 µg/mL for both drugs, with detection limits of 0.55 µg/mL (CLB) and 0.67 µg/mL (TRD). The method showed excellent selectivity in the presence of common co-formulated drugs and was successfully applied to determine both analytes in commercial Seglentis^® tablets. This developed method provides a rapid, accurate, and cost-effective solution for routine quality control of complex pharmaceutical formulations.

The development of low-cost, efficient and stable electrocatalysts for oxygen reduction reaction is critical for advancing energy conversion and storage technologies. The oxygen reduction reaction (ORR) is a key electrochemical process in energy conversion systems, particularly in fuel cells, where it governs the overall efficiency of the device. This study explores the electrochemical performance of a novel carbon paste electrode (CPE) modified with silica fume (SF), polyaniline (PANi), and iron nanoparticles (FeNPs) for potential application in fuel cells and supercapacitors. A stepwise electrode modification approach was employed to fabricate CPE/SF, CPE/SF/PANi, and CPE/SF/PANi/FeNP nano-composite electrodes. The structural and morphological characteristics of the modified electrodes were analyzed using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Raman spectroscopy. Electrochemical properties were assessed via cyclic voltammetry (CV), linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS), and chronoamperometry (CA). The incorporation of PANi and FeNPs significantly enhanced the electrocatalytic activity of the electrode, as evidenced by increased current densities and reduced onset potentials in methanol oxidation and oxygen evolution reactions (OER). EIS data demonstrated a marked decrease in charge transfer resistance, indicating improved electrical conductivity. The results confirmed that the reactions were diffusion-controlled. Chronoamperometric analysis further revealed superior long-term stability and resistance to electrode poisoning in the FeNP-modified electrodes. The addition of SF resulted in a substantial 7.235-fold increase in current density, with the initial values determined as 1.089 mA cm⁻² for CPE/PANi and 7.879 mA cm⁻² for CPE/PANi/SF.These results highlight the synergistic effects of combining SF, PANi, and FeNPs, offering promising prospects for use in energy-related applications.

This study examined the adsorption of the mechlorethamine (ME) anti-cancer drug loaded upon Mg₁₂O₁₂ nanocage using DFT: B3LYP (6-31G* and 6-311G** basis set) and B3PW91 (6-31G* basis set) calculations. To clarify the electronic, thermochemical, and structural properties of drug (ME) complexes with Mg₁₂O₁₂ nanocages, DFT calculations were combined with the Quantum Theory of Atoms in Molecules (QTAIM) study. NBO analysis revealed that the maximum stability energy of the electronic transfer of ME into Mg₁₂O₁₂ nanocavities originated from the LP(1)N27 to LP*(1)Mg5 transition with an E2 value of 17.63 kcal mol. Further, the maximum stability energy value obtained from Mg₁₂O₁₂ nanocages to the drug ME was owing to the electronic shift from LP*(1) Mg 5 to σ*C 31—H 41 orbitals compared to the drug/nanotube complex with E2 = 0.81 kcal.mol-1. Based on the QTAIM results, -G(r)/V(r) value ​​for the interaction between the H41 atom of the ME drug and the O13 atom of the nanocage [(C31-H41 (ME)…O13 (nanocage)] was about 0.37, indicating the covalent nature of the interaction. In the UV–Vis spectrum, the wavelength shift from 198 to 258 nm with the adsorption of the drug on the nanosorbent revealed a bathochromic change (red shift). The values ​​of ∇2ρ and ρ are associated with hydrogen bonds between atoms H41 and O13 (∇2ρ = 0.0602; ρ = 0.0208) as well as atoms O15 and H43 ∇2ρ = 0.0525; ρ = 0.0179). Thus, the interactions mentioned in this series are related to hydrogen bonds. Accordingly, based on the results obtained, Mg₁₂O₁₂ nanoclusters can be used as a promising carrier for ME drug delivery.

Graphical Abstract

In this study, seven new Mannich bases 4a-g, containing 1,2,4-triazole and 2,6-dimethylmorpholine were synthesized and characterized by ¹³C-NMR, ¹H-NMR and IR spectroscopy. Newly synthesized compounds’ antioxidant characteristics were assessed with three different techniques (Reducing Power, Metal Chelation Activity, and Free Radical Scavenging). These compounds were also evaluated for their antimicrobial activity against 6 different bacteria. In vitro studies revealed that the synthesized compounds exhibited high metal chelating activity due to the presence of -OH, C = O, -NR₂, and -O- groups, despite their low free radical scavenging and reducing activity. Furthermore, antibacterial tests revealed that compound 4e, in particular, exhibited potent activity against six different bacterial species, demonstrating its potential as an antimicrobial agent. These results suggest that these compounds possess significant biological activities that may influence both metal ion chelating and microbial growth. These new Mannich bases were evaluated for their drug availability and absorption, distribution, metabolism, and excretion (ADME) properties using the SwissADME tool. ADME analysis results showed that the newly synthesized compounds could find application in the field focused on the production of effective and harmless pharmacological drugs. Molecular docking analysis was performed to investigate the potential Alzheimer’s disease activities of the newly synthesized compounds with BChE (PDB: 6SAM) and GST (PDB: 5J41) enzymes. In molecular docking analysis, compound 4d with enzyme 6SAM (docking score − 9.91) and compound 4e with enzyme 5J41 (docking score − 8.37) among the synthesized compounds showed good results on potential Alzheimer’s disease. In addition, SAR analysis was performed by calculating the HOMO-LUMO, ΔE values of the new compounds with DFT. SAR analysis results were compared with ADME, molecular docking analysis, and antimicrobial activity results. The high metal chelation and antimicrobial activities obtained in this study were consistent with the DFT-based HOMO-LUMO energy differences (ΔE) calculated from the electronic structures of the compounds. In particular, compounds with low energy differences exhibited both high binding affinity to target enzymes in molecular docking studies and effective results in biological assays, demonstrating a strong correlation between experimental findings and theoretical calculations. This consistency demonstrates that the biological activities of compounds are directly related to their molecular electronic properties and that computational approaches can guide the design of effective compounds.

This study presents the development and validation of a fluorescence-based high-performance liquid chromatography (HPLC) method for the quantification of alectinib in rat plasma, with a focus on the application of Analytical Quality by Design (AQbD) to bioanalytical method development. Unlike conventional QbD applications, which primarily address synthetic formulations or instrumental settings, this study systematically applied AQbD principles to the complex environment of biological matrices. Critical method parameters, including the organic phase ratio, buffer concentration, and flow rate, were identified through Failure Mode and Effects Analysis, and optimized using a Box–Behnken design. The final method exhibited excellent linearity (R² >0.99) over a concentration range of 5–1,000 ng/mL, with a lower limit of quantification of 5 ng/mL. It also showed high accuracy (95.6–102%), precision (relative standard deviation < 11%), and consistent recovery (98.3–105%), with minimal matrix effects. Alectinib stability was confirmed under various handling conditions. This method was successfully applied in a pharmacokinetic study after intravenous and oral administration of alectinib in rats. These results highlight the value of AQbD in addressing specific challenges of bioanalysis and demonstrate its utility in establishing a sensitive, robust, and regulatory-compliant method suitable for pharmacokinetic applications.