BMC Chemistry最新文献

Background

Pantoprazole (PAN) is a proton pump inhibitor used to treat GERD and hyperacidity by suppressing gastric acid secretion, effectively relieving symptoms such as heartburn, acid regurgitation, and indigestion. Domperidone (DOM) is a prokinetic agent that enhances gastrointestinal motility, helping to alleviate nausea, vomiting, and bloating caused by motility disorders. Their combination (Pantosec-D) provides rapid and comprehensive relief from both acid-related and motility-related symptoms, significantly improving patient comfort and quality of life.

Objective

This study aims to develop and validate three eco-friendly spectrophotometric techniques—ratio difference (RD), first derivative (1DD), and mean centering (MC) of ratio spectra—for the simultaneous determination of PAN and DOM in pharmaceutical formulations.

Method

The proposed methods resolve spectral overlap through ratio spectra manipulation. In the RD method, DOM is quantified by measuring the amplitude difference at 209 nm and 233 nm, while PAN is determined at 254 nm and 223 nm. The ¹DD method detects DOM at 215 nm and PAN at 249 nm, whereas the MC method quantifies PAN at 254 nm and DOM at 209 nm.

Results

The suggested methods were validated according to ICH regulations. Pharmaceutical formulations comprising PAN and DOM were effectively analyzed using the linear correlations obtained for both drugs over concentration ranges of 0.5–52 µg/mL and 1–18 µg/mL, respectively.

Conclusion

Compared with reported spectrophotometric techniques, ratio methods are especially beneficial for routine pharmaceutical analysis due to their ease of use, capacity for handling overlapping spectra, and robustness to experimental variations. Compared with reported chromatographic methods, these techniques provide easy-to-use, reasonably priced, less solvent, and dependable substitutes for the standard quality control of these medications in pharmaceutical dosage forms.

A novel sedative/hypnotic drug called suvorexant (SUV) is advised for treating insomnia. From a forensic standpoint, it is important medicine because of its sedative/hypnotic and depressing effects. There are no green “high-performance thin-layer chromatographic (HPTLC)” techniques for measuring SUV in the literature. Therefore, this study aims to develop and validate a reverse-phase HPTLC approach that indicates green stability for SUV measurement in commercially available tablet dosage forms. SUV was detected at 255 nm in wavelength. The suggested SUV analysis approach’s greenness was assessed using the “analytical eco-scale (AES), ChlorTox, and analytical GREEnness (AGREE)” tools. The current SUV analysis method showed linearity in the 10–1200 ng/band range. Furthermore, the SUV analytical method was robust, accurate (% recoveries = 98.18–99.30), sensitive (LOD = 3.32 ng/band and LOQ = 9.98 ng/band), precise (% CV = 0.78–0.94), and environmentally friendly. The “AES, total ChlorTox, and AGREE” scales were derived to be 93, 0.96 g, and 0.88, respectively, using the current SUV analytical method, demonstrating an exceptional greenness profile. SUV was shown to be suitably unstable under oxidative degradation conditions and suitably stable under acid, base, and heat degradation conditions. Furthermore, the SUV analytical method’s stability-indicating component identified SUV in the presence of its breakdown products. It was observed that marketed SUV tablet brands A and B contained, respectively, 98.18 and 101.32% of SUV. The findings of the study indicated that SUV in marketed tablet dosage forms may be monitored on a regular basis with the use of the current green HPTLC methodology.

Head and neck squamous cell carcinoma (HNSCC) is the most common head and neck cancer and highly aggressive and heterogeneous. Targeted therapy is still the main treatment method used in clinic due to lower side effect and personalized medication. In order to discover novel and effective drugs with low side effect against HNSCC, we analyzed the genes related to HNSCC, and found that PIK3CA was highly expressed in tumor tissues and often experienced mutations, leading to excessive activation of phosphoinositide 3-kinase alpha (PI3Kα), promoting the development of HNSCC. The allosteric PI3Kα inhibitor STX-478 inhibits the growth of tumor with hotspot mutations in PI3Kα and shows prominent efficacy on the treatment of human HNSCC xenografts without displaying the metabolic dysfunction observed in Alpelisib. These mutations open the allosteric site more readily, increasing the selectivity of STX-478 for mutant PI3Kα. STX-478 cleverly avoids the side effect of ATP competitive PI3Kα inhibitors. So, the structure of STX-478 was optimized based on the interaction mechanism between STX-478 and PI3Kα. Then, virtual screening, binding mode research, target verification, physical and chemical properties, pharmacokinetic properties and stabilities of ligand-PI3Kα complexes were evaluated by computer technologies (scaffold hopping, cdocker, SuperPred, SwissTarget prediction, Lipinski’s rule of five, ADMET and MD simulation). Finally, J-53 (2-oxopropyl urea compound) with excellent properties was selected. J-53 not only formed H-bonds with key amino acids, but its unique -C(O)CH₃ could also form H-bonds with ILE1019, making it more stably bound to PI3Kα and contributing to its activity. After the SciFinder verification, J-53 with novel structure had the value of further study. This study suggested that J-53 could be used as potential inhibitors of PI3Kα, and provides valuable information for the subsequent drug discovery of allosteric PI3Kα inhibitors.

Graphical Abstract

Carbon sequestration by application of organic materials and biochar in soil is an important strategy to increase soil organic carbon (SOC), but the stability of SOC, particularly humic substances (HS) vary with the types of organic material. In this study, cotton straw and its derived compost and biochar were added with equivalent carbon content to soil and incubated for 180 days. The structural characteristics of humic acid (HA), fulvic acid (FA) and humin (Hu) were investigated using solid-state ¹³C nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy. The results showed that biochar treatment increased the aryl C of HA, FA, and Hu by 1.38%, 1.68%, and 10.46% compared to straw treatment and increased the aryl C of HA, FA, and Hu by 1.46%, 1.99% and 2.01% compared to compost treatment. The O-alkyl C of HA was 10.59% and 10.65% in high biochar/straw and biochar/compost ratios respectively, while it was 9.81% and 9.61% in low biochar/straw and biochar/compost ratios. In addition, the O-alkyl C of FA was 62.83% and 58.48% in high ratios of biochar/straw and biochar/compost, respectively, while it was 55.85% and 55.94% in low ratios of biochar/straw and biochar/compost. These results suggest that biochar is advantageous for aryl C formation of FA and Hu due to its high aryl C content, whereas straw or compost is advantageous for alkyl C formation of HA. The stability of aryl C and O-alkyl C of HA, FA, and Hu can be improved in soils by incorporating biochar in combination with straw or compost.

Graphical abstract

Bone regeneration is one of the most effective methods for treating bone defects. In this work, tricarboxylic cellulose/sodium alginate loaded with hydroxyapatite (HA) and/or graphene oxide (GO) was coagulated by calcium ions to create beads as scaffolds. In the first, cellulose was oxidized to water-soluble tricarboxylic cellulose (TCC) by 2,2,6,6‐tetramethylpiperidine-1-oxyl (TEMPO), periodate, and chlorite oxidation. HA was extracted from eggshells via microwave treatment, and GO was synthesized using the Hummer method. The structural behavior of the formed beads was meticulously investigated through various characterization techniques such as Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The SEM images confirmed the formation of particles of micrometric size without any specific morphology. Incorporating GO or HA does not affect the morphologies of the materials on the micrometric scale. The cytocompatibility of different bead preparations was studied on murine mesenchymal stem cells. Moreover, the swellability in water and biodegradability by cellulase enzyme of prepared beads were studied. The results show that the prepared beads may be promising for bone tissue engineering.

Bruton’s tyrosine kinase (BTK) inhibitors play a critical role in the treatment of mantle cell lymphoma (MCL). pirtobrutinib, a new, highly selective, non-covalent BTK inhibitor, was approved by the FDA for the treatment of MCL, chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL). In this study, we established a robust and reliable method for the quantitation of pirtobrutinib in rat plasma using ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Acetonitrile and 0.1% formic acid served as the mobile phase, with zanubrutinib as the internal standard (IS). Detection ion transitions were m/z 480.12→294.05 for pirtobrutinib and m/z 472.20→ 289.96 for Zanubrutinib. The intra‐day and inter‐day relative standard deviation (RSD%) values of pirtobrutinib were less than 9.8% and 10.3%, respectively. Recovery and matrix effects ranged from 95.1 to 101.5% and 91.7-100.4%. In addition, the test sample stability was confirmed under various storage conditions, and this method was successfully applied to a pharmacokinetic study of pirtobrutinib at a dose of 10 mg·kg^− 1.

To elucidate the mechanism by which choline-based ionic liquids potentially can enhance the sugar conversion to bioethanol, this work was conducted to study the thermodynamic behavior of D( +)-glucose in aqueous solutions of choline-based ionic liquids, choline salicylate [Ch][Sal], choline formate [Ch][For], and choline acetate [Ch][Ace]. This study involved measuring density, speed of sound, viscosity, and electrical conductivity at various concentrations and temperatures. Analysis of the calculated parameters, including apparent molar volume, V_φ, apparent molar isentropic compressibility (κ_φ), viscosity B-coefficient, and molar conductivity (Λ) values provide deep insights into intermolecular interactions between the components of the solutions studied. The standard partial molar volume values ((V_{varphi }^{0})) of D( +)-glucose, show stronger interactions between D( +)-glucose and the [Ch][Sal]. The computed transfer volume values ((Delta_{tr} V_{varphi }^{0})), with the help of co-sphere overlap model confirm intensified hydrophilic-hydrophilic interactions in [Ch][Sal] [(1.99 to 2.08) cm³·mol⁻¹] solutions. Hepler's constants suggest that D( +)-glucose acts as a structure-maker in the presence of choline-based ILs, especially in [Ch][Sal] solutions. Also, the DFT-COSMO calculations result in [Ch][Sal] the most favorable interactions among the other choline based ILs. Apparent specific volume (ASV), and apparent specific isentropic compressibility, (ASIC), values revealed that D( +)-glucose exhibits the taste behavior with [Ch][Sal]. The hydration number of D( +)-glucose diminishes as the temperature rises due to weakened hydrogen bonds between D( +)-glucose and water molecules. These findings suggest that [Ch][Sal] could be a promising candidate for accelerating sugar conversion to bioethanol.

Graphical Abstract

A successful methodology for the copper-catalyzed dehydrogenated methylsulfonylation of alkenes utilizing CH₃SSO₃Na in conjunction with hypervalent iodine reagents was successfully established. This method offers a practical avenue to obtain allyl methyl sulfones and alkenyl methyl sulfones by forming C-S bonds. Using the C-H bond oxidation sulfonylation strategy with alkenes and Bunte salts, we successfully synthesized a total of twenty two compounds, including four examples of deuterium-substituted molecules, and demonstrated one example of a scale-up reaction.

Graphical abstract

A new series of 1-substiuted-5,6-dichloro-2-(4-methoxyphenyl)-1H-benzo[d]imidazoles 10a–p was designed and synthesized to target both BRAF_WT and BRAF_V600E. The design strategy ensures that these derivatives would effectively occupy the ATP binding pocket of BRAF_WT/V600E kinase domains and extend over the gate area interacting through hydrogen bonding with the surrounding key amino acids Glu500 and Asp593 and to finally occupy the allosteric hydrophobic back pocket. Some synthesized derivatives demonstrated impressive potency against BRAF_WT with % inhibition approaching 91% at a concentration of 10 µM. The most potent candidate 10h demonstrated IC₅₀ values of 1.72 and 2.76 µM on BRAF_WT and BRAF_V600E, respectively. At the same time, the synthesized benzimidazoles 10a–p were examined for their growth inhibitory activity on NCI-60 cancer cell lines. Again, compound 10h revealed a potent GI₅₀ across a range of cancer cell lines. Moreover, it arrested cell cycle progression in HT29 colon cancer cell line at G2/M phase and induced apoptosis in the same cell line. Molecular dynamics simulations supported the validity of the design assumption, simultaneously, ADME prediction study displayed that the designed benzimidazoles exhibit promising physiochemical and drug-likeness properties as anticancer agents.

Graphical Abstract