The enantioselective binding of three proton pump inhibitors (PPIs)—omeprazole, rabeprazole, and lansoprazole—to two key plasma proteins, α1-acid glycoprotein (AGP) and human serum albumin (HSA), was characterized. The interactions between PPI enantiomers and proteins were investigated using a multifaceted analytical approach, including high-performance liquid chromatography (HPLC), fluorescence and UV spectroscopy, as well as in silico molecular docking. HPLC analysis demonstrated that all three PPIs exhibited enantioseparation on an AGP-based chiral stationary phase, suggesting stereoselective binding to AGP, while only lansoprazole showed enantioselective binding on the HSA-based column. Quantitatively, the S-enantiomers of omeprazole and rabeprazole showed higher binding affinity to AGP, while the R-enantiomer of lansoprazole displayed greater affinity for AGP, with a reversal in the elution order observed between the two protein-based columns. Protein binding percentages, calculated via HPLC, were greater than 88% for each enantiomer across both transport proteins, with all enantiomers displaying higher affinity for AGP compared to HSA. Thermodynamic analysis indicated that on the HSA, the more common, enthalpy-controlled enantioseparation was found, while in contrast, on the AGP, entropy-controlled enantioseparation was observed. The study also identified limitations in using fluorescence titration due to the high native fluorescence of the compounds, whereas UV titration was effective for both proteins. The determined logK values were in the range of 4.47–4.83 for AGP and 4.02–4.66 for HSA. Molecular docking supported the experimental findings by revealing the atomic interactions driving the binding process, with the predicted enantiomer elution orders aligning with experimental data. The comprehensive use of these analytical methods provides detailed insights into the enantioselective binding properties of PPIs, contributing to the understanding of their pharmacokinetic differences and aiding in the development of more effective therapeutic strategies.

/Purpose: Online vendors seize the advantage of the high demand on home-use, do-it-yourself dental bleaching products. The study aims to present the uncontrolled online market of dental products and provide evidence of consumer safety risks associated with the utilization of high peroxide content bleaching products without dentist's supervision, and also to identify misleading and insufficient information on content and compromised product quality. A complex risk-based methodology was used including website content evaluation focusing on ingredients, precautionary statements and directions for use provided by online retailers. Bleaching products were test procured in which packaging and labels were documented and assessed. Quality control was performed using the permanganometric method per the official European Pharmacopoeia. One (16.7%) of six test procured peroxide gels was not delivered. Another arrived without enclosed description or instructions. The ingredient list was incomplete or missing for all (100%) online products, however, it was listed on the label or in enclosed documentation in four out of five (80%) samples. Precautionary statements were scarcely (16.7%) disclosed online, contrarily, safety claims were emphasized by most (83.3%) websites. Contraindications and adverse effects were mentioned in the majority (80%) of the delivered product labels. One sample contained no active principle, in two sample’ peroxide content exceeded the label's claim by 5.2–9.0% while in another two it was below the concentration indicated on the labels by 79.9–80.7%. Dissimilarity in regulations elicits an opportunity for consumers to purchase inappropriately labeled, questionable quality, high peroxide content dental products without information regarding ingredients, application and risks. The uncontrolled market, easy access and unsupervised application of high peroxide-content teeth whiteners imply patient safety issues.

Background: Phenolic Mannich bases derived from hydroxychalcones show remarkable cytotoxic potencies towards cancer cell lines. However, the exact mechanism of action is still partially uncleared. Objective: Interaction of two hydroxychalcones and their Mannich derivatives with calf thymus DNA (ctDNA) has been investigated. Methods: Thin-layer chromatography and UV-Vis spectroscopic method were used for studying the interaction. The binding constant has been determined by UV-Vis spectrophotometric titration. The DNA cleavage activity of the compounds was studied by agarose gel electrophoresis. Results: Interaction of the compounds with ctDNA exhibited relatively high intrinsic binding constant (4-5x10⁴ M^-1). The results indicate existence of weak, non-covalent interactions between the investigated derivatives with ctDNA. Some compounds showed a slight DNA cleavage activity with pBR322. Conclusion: The obtained results provide additional knowledge on the previously documented cytotoxicity against tumor cell lines of the hydroxychalcones and their Mannich-derivatives.

Interaction of some cyclic chalcone analogs, (E)-2-(4-X-benzylidene)-1-benzosuberone derivatives with bovine serum albumin (BSA) and human serum albumin (HSA) has been investigated using UV-Vis spectroscopic methods. Recording the UV-Vis spectra of compounds in the presence of BSA or HSA indicated interaction of the molecules with the hydrophobic binding site(s) of the proteins. Investigated analogs have shown remarkable topo I and topo II inhibitory activity compared to camptothecin and etoposide, respectively, at 40 μM concentration. The observed interactions between the cyclic chalcone analogs and the cellular macromolecules might play a role in the previously detected cytotoxicity against several tumor cell lines.