BMC Chemistry最新文献

Acinetobacter baumannii has become a notable “superbug” due to its rapid development of resistance to multiple classes of antibiotics. This study aimed to evaluate the antibacterial and antibiofilm effectiveness of gentamicin-loaded solid lipid nanoparticles (GM-SLNs) in treating infections caused by A. baumannii. Nanoparticles were synthesized using the double melt emulsion dispersion method. A. baumannii was isolated from wounds, blood, urine, and sputum through standard microbiological techniques. Antimicrobial susceptibility was tested using the Kirby-Bauer disk diffusion method. The biofilm-forming ability of A. baumannii isolates, the antibacterial activity of GM-SLNs, and the time killing assay were conducted following standard protocols with slight modifications. The impact of GM-SLNs on the expression of biofilm-related genes was analyzed using real-time PCR. A total of 37 A. baumannii strains were isolated from 41 clinical specimens. The most common antibiotic resistances were against gentamicin (GM), ciprofloxacin (CIP), ceftazidime (CAZ), and imipenem (IMP). 80% of the A. baumannii isolates were classified as multidrug-resistant (MDR). GM-SLNs reduced the minimum inhibitory concentrations (MICs) for all A. baumannii strains twofold, fourfold, and even up to eightfold compared to free GM. GM-SLNs were also significantly more effective than free GM in inhibiting biofilm formation in all A. baumannii isolates. Furthermore, the expression of the bap gene was significantly lower in all isolates treated with GM-SLNs compared to those treated with free GM. Overall, GM-SLNs represent a major breakthrough in the fight against A. baumannii and other biofilm-related infections, providing hope for more effective treatment options amid the growing challenge of antimicrobial resistance.

Optimizing the extraction of natural products is an important step to obtain products rich in bioactive compounds with less energy use and costs. The aim of this study was to optimize the ultrasonic extraction process of poplar type propolis with natural deep eutectic solvent (NADES) citric acid:1,2-propanediol 1:4 (CAPD 1:4). Based on preliminary experiments, the extraction parameters solvent to solid ratio, temperature, and time were found to have a strong positive effect on the extraction of phenolic compounds, and they were further optimized by response surface methodology (RSM) via the Box-Behnken design (BBD). Solvent to solid ratio of 30 mL/g, ultrasonication time of 39 min and temperature of 65 °C were determined as optimum conditions for the highest values of total phenolic content (TPC, 290.35 mg/g), total flavones and flavonols content (TFC, 89.48 mg/g) and radical scavenging activity (31.89%RSA). The optimized extract was analyzed by gas chromatography-mass spectrometry (GC-MS) and a high relative content of valuable propolis constituents was found such as pinocembrin, 3-acetylpinobanksin, chrysin, galangin and phenethyl caffeate (CAPE). The results provide knowledge about optimal conditions for the development of a greener extract of poplar type propolis rich in valuable bioactive compounds with potential application in cosmetic, nutraceutical and pharmaceutical industries.

Chemical fixation of CO₂ into 2-oxazolidinones is of significance because of the important application in the chemical synthesis. In this study, a series of ionic liquid functionalized SiO₂ nanocomposites were synthesized and developed as heterogeneous catalysts for the CO₂ cyclization reaction. The resulting SiO₂-MILZrCl₅ behaved as high-efficiency heterogeneous catalyst for solvent-additive-free CO₂ cyclization at 70 °C and 0.1 MPa CO₂. A high yield of 93% with selectivity of 99.4% over 5-methyl-3-phenyloxazolidin-2-one was attained. Furthermore, a wide range of epoxides were transformed with high yields and excellent selectivities under atmospheric pressure. Additionally, SiO₂-MILZrCl₅ could serve as a durable and recoverable heterogeneous catalyst for the reaction, which could be used for five cycles without significant loss of catalytic activity. This study offers novel insights for the development of green catalysts for the efficient CO₂ fixation.

Graphical Abstract

The fatty acid-binding protein 1 (FABP1) has drawn increasing attention as a promising target for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). However, efforts to validate pharmacological effects of FABP1 are restricted by the lack of relevant inhibitors. Herein, we identified the lead compound 1 with potent inhibition on FABP1 through screening from our in-house library. Further comprehensive structure-activity relationship (SAR) study based on compound 1 resulted in the identification of the optimal compound 12 (IC₅₀ = 3.6 µM). Moreover, compound 12 exerted stronger efficacy on reducing hepatic lipid accumulation, inflammation and fibrosis than that of clinical candidate GFT505 in MASH models. In addition, compound 12 significantly inhibited fibrosis-related gene expression in TGF-β treated hepatic stellate cells and exerted stronger effects than Pirfenidone in CCl₄-induced liver fibrosis mice model. These results indicated that compound 12 may serve as a novel FABP1 inhibitor for the treatment of MASH and liver fibrosis.

Background

Establishing an analytical method for the detection of related substances in ketoconazole cream is essential for improving product quality standards and ensuring the safety of this formulation.

Methods

In the 2024 National Drug Sampling Specification, we developed a novel high-sensitivity high-performance liquid chromatography (HPLC) method that effectively separates six known impurities, four preservatives, and one antioxidant present in ketoconazole creams. These creams were sourced from random market sampling and exhibited variations in prescription composition across 14 different manufacturers. Subsequently, we conducted the extraction, isolation, and characterization of common unknown impurities from these creams using mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and infrared (IR) techniques. Furthermore, the structural analysis of unknown impurities within a specific enterprise was performed using high-resolution mass spectrometry and specialized software.

Results

The established method has been thoroughly validated, demonstrating its specificity, accuracy, sensitivity, and excellent repeatability, thereby confirming its suitability for determining related substances in ketoconazole creams from various manufacturers. This method allowed for both quantitative and qualitative evaluations of impurity content across different manufacturers, identifying sulfonated impurities in ketoconazole creams for the first time and analyzing their formation mechanisms. Furthermore, strategies to reduce these impurities were proposed through correlation analysis and process validation. Additionally, this study innovatively introduced a solvent smoothing agent to mitigate solvent effects, thereby preventing the degradation of the active pharmaceutical ingredient (API) during the heating and dissolution process of the cream matrix. This technique is applicable to the pretreatment of various cream-related substance determinations.

Conclusions

This method provides substantial reference value for establishing analytical methods for related substances in Ketoconazole cream and offers technical support for regulatory agencies in evaluating the quality of Ketoconazole cream.

Carbonic anhydrase IX (CA IX) is a hypoxia-induced pH regulator whose over-expression drives tumor progression and therapy resistance. Most CA inhibitors rely on zinc chelation and lack isoform selectivity, limiting clinical utility. Here we combined structure-based docking, 200 ns molecular-dynamics simulations and steady-state enzyme kinetics to assess four rare sulfonamide/sulfone natural products (altemicidin, SB-203207, SB-203208 and sulfadixiamycin A) as non-classical CA IX blockers. Docking located every ligand at the mouth of the catalytic funnel (− 7.2 to − 9.4 kcal mol⁻¹) without coordinating Zn²⁺. MD-derived free-energy landscapes and MM/PBSA calculations confirmed durable entrance-bound complexes for SB-203207/208 and sulfadixiamycin A (ΔG_total ≈ − 24 to − 27 kcal mol⁻¹) but frequent dissociation of altemicidin ( ≈ − 2 kcal mol⁻¹). Per-residue-decomposition pinpointed a hydrophobic wall (Leu91, Val121, Phe131, Leu198, Pro202, Phe243) plus anchoring H-bonds to Thr199 and Gln92. Recombinant-enzyme assays validated these predictions: SB-203207, SB-203208 and sulfadixiamycin A inhibited CA IX esterase activity with IC₅₀ = 73 ± 1, 99 ± 2, and 114 ± 3 nM, respectively, versus 41 ± 1 nM for reference acetazolamide. Crucially, SB-203207 showed marked selectivity, with SI = 28 (hCA I/IX) and SII = 14 (hCA II/IX), far exceeding the > 10-fold benchmark; SB-203208 and sulfadixiamycin A also met this threshold, whereas altemicidin was both weaker (1.90 µM) and less selective. Steady-state esterase kinetics were consistent with non-competitive inhibition and K_i values that mirrored the IC₅₀ rank order. SwissADME/ADMETlab profiling highlighted SB-203207 as the most developable hit. Together, these results establish entrance-channel plugging as an alternative mechanism for CA IX inhibition, identify SB-203207 as a potent and isoform-selective lead.

Two sensitive and selective ion-selective electrodes (ISEs) were developed for the determination of benzydamine hydrochloride (BNZ·HCl): a conventional polyvinyl chloride (PVC) electrode and a coated graphite all solidstate ion-selective electrode (ASS-ISE). Both sensors were constructed using an ion-pair formed between BNZ⁺ and the lipophilic anion tetraphenylborate (TPB⁻), incorporated into the sensing membranes. The sensors exhibited near-Nernstian responses with slopes of 58.09 And 57.88 mV/decade, over a Linear range of 10^–5–10^–2 M, and detection Limits of 5.81 × 10^–8M and 7.41 × 10^–8 M, respectively. They demonstrated high accuracy and precision for the determination of BNZ·HCl in pure form, pharmaceutical cream, and biological fluids, with no matrix interference. The method also proved stability-indicating, successfully detecting BNZ·HCl in the presence of its oxidative degradant. Validation was performed according to ICH guidelines, and the method showed strong environmental compatibility based on greenness, whiteness, and blueness assessments, supporting its suitability for sustainable pharmaceutical analysis.

The widespread clinical utilization of amlodipine-aspirin combinations, despite potential pharmacodynamic interactions and the high prevalence of drug-drug interactions in cardiovascular patients, necessitates robust analytical methods for pharmaceutical quality control and therapeutic drug monitoring. Current analytical approaches face limitations including lengthy analysis times, substantial solvent consumption, and high operational costs. This study presents a novel spectrofluorimetric method coupled with genetic algorithm-enhanced partial least squares (GA-PLS) regression for simultaneous quantification of amlodipine and aspirin in pharmaceutical formulations and biological plasma samples. Synchronous fluorescence spectroscopy at Δλ = 100 nm in 1% sodium dodecyl sulfate-ethanolic medium enhanced spectral characteristics, while chemometric approaches were essential to address remaining spectral overlap for accurate quantification. The GA-PLS approach demonstrated superior performance over conventional partial least squares regression, achieving relative root mean square errors of prediction (RRMSEP) of 0.93 and 1.24 for amlodipine and aspirin respectively, with limits of detection of 22.05 and 15.15 ng/mL. Genetic algorithm optimization reduced spectral variables to approximately 10% of the original dataset while maintaining optimal model performance with only two latent variables. Method validation according to ICH Q2(R2) guidelines demonstrated excellent accuracy (98.62–101.90% recovery) and precision (RSD < 2%) across the analytical range of 200–800 ng/mL. Statistical comparison with established HPLC reference methods showed no significant differences, while application in human plasma achieved recoveries of 95.58-104.51% with coefficient of variation below 5%. Multi-dimensional sustainability assessment using the MA Tool and RGB12 whiteness evaluation achieved an overall score of 91.2%, demonstrating clear superiority over conventional HPLC-UV (83.0%) and LC-MS/MS (69.2%) methods across environmental, analytical, and practical dimensions. The developed method provides a sustainable, cost-effective alternative for routine pharmaceutical analysis, demonstrating enhanced performance through intelligent variable selection and improved operational efficiency.

An efficient, reliable, and cost-effective approach was applied for the electrochemical synthesis of spirooxindole-pyranopyrazole and spirooxindole-chromene derivatives. The compounds were prepared in high yields and short reaction times by electrochemical synthesis using LiClO₄ as an electrolyte and Cu/graphite as electrodes. The synthesized products were tested as acetylcholinesterase (AChE) inhibitors. Compounds 4e and 6b demonstrated potent inhibitory activity against AChE enzyme with IC₅₀ values of 0.51 and 0.84 mM, respectively. Both compounds showed low cytotoxicity and preserved normal cell morphology, confirming their safety. The in-silico study of the ADME properties of compounds 4e and 6b revealed a high bioavailability score without affecting any of the CYP isoforms. Kinetic studies were performed to detect the mode of inhibition of the most active compounds, 4e and 6b. Also docking studies were performed for both compounds, to evaluate their binding patterns compared to donepezil. The docking and kinetic studies indicated that both compounds inhibited AChE through a competitive mechanism predominantly targeting the catalytic anionic site CAS.