This research focuses on the development and validation of a capillary electrophoresis (CE) method for the chiral separation of three H1-antihistamine drugs chlorcyclizine, norchlorcyclizine, and neobenodine using sulfated β-cyclodextrin (S-β-CD) as the chiral selector. The study explores various factors influencing the separation efficiency, including CD concentration, organic modifier content, voltage application, and buffer pH. Optimal conditions were identified as a 100 mM phosphate buffer (pH 6.0) with 34 mg mL-1 S-β-CD and 40% (v/v) methanol. The method demonstrated excellent linearity in calibration curves, with coefficients of determination exceeding 0.99 for each enantiomer. Precision studies revealed good intra- and inter-day precision for migration times and peak areas. The limits of detection and quantification for the analytes were within the ranges of 5.9-11.4 and 18-34.6 µmol L-1, respectively. Overall, the developed CE method offers a robust and precise approach for the chiral separation of H1-antihistamine drugs, holding promise for pharmaceutical applications.

• Klíčová slova
• capillary electrophoresis, chiral separation, methanol, piperazine derivatives, sulfated β‐cyclodextrin,
• MeSH
• beta-cyklodextriny * chemie   MeSH
• elektroforéza kapilární * metody   MeSH
• koncentrace vodíkových iontů MeSH
• limita detekce * MeSH
• lineární modely MeSH
• piperaziny chemie   analýza   MeSH
• reprodukovatelnost výsledků MeSH
• sírany chemie   analýza   MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny * MeSH
• piperaziny MeSH
• sírany MeSH

The incorporation of phosphorothioate linkages has recently been extensively employed in therapeutic oligonucleotides. For their separation and quality control, new high-efficient and high-sensitive analytical methods are needed. In this work, a new affinity capillary electrophoresis method has been developed and applied for the separation of a potential anticancer drug, 2',3'-cyclic diadenosine diphosphorothioate (Rp, Rp) (ADU-S100), and three recently newly synthesized diastereomers of its difluorinated derivative, 3',3'-cyclic di(2'-fluoro, 2'-deoxyadenosine phosphorothioate). The separation was performed in the various background electrolytes (BGEs) within a pH range 5-9 using several native and derivatized cyclodextrins (CDs) as chiral additives of the BGE. Relatively good separations were obtained with β-, γ-, and 2-hydroxypropyl-γ-CDs in some of the BGEs tested. However, the best separation was achieved using the 2-hydroxypropyl-β-CD chiral selector at 43.5 mM average concentration in the BGE composed of 40 mM Tris, 40 mM tricine, pH 8.1. Under these conditions, all the previous four cyclic dinucleotides (CDNs) were baseline separated within 4 min. Additionally, the average apparent binding constants and the average actual ionic mobilities of the complexes of all four CDNs with 2-hydroxypropyl-β-CD in the above BGE were determined. The formed complexes were found to be relatively weak, with the average apparent binding constants in the range of 12.2-94.1 L mol-1 and with the actual ionic mobilities spanning the interval (-7.8 to -12.7) × 10-9 m2 V-1 s-1. The developed method can be applied for the separation, analysis, and characterization of the above and similar CDNs.

• Klíčová slova
• affinity capillary electrophoresis, binding constant, chiral analysis, cyclic dinucleotides, cyclodextrins,
• MeSH
• beta-cyklodextriny * chemie   MeSH
• dinukleosidfosfáty chemie   izolace a purifikace   analýza   MeSH
• elektroforéza kapilární * metody   MeSH
• hydroxypropyl beta cyklodextrin * chemie   MeSH
• koncentrace vodíkových iontů MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny * MeSH
• dinukleosidfosfáty MeSH
• hydroxypropyl beta cyklodextrin * MeSH

The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice. CHO cell viability was examined after lipid raft disruptor treatments and their effects on channel activation on channel expressing HEK293T cells by measurement of cytoplasmic Ca2+ concentration were monitored. The effects of treatments were investigated in Pregnenolone-Sulphate-CIM-0216-evoked and icilin-induced acute nocifensive pain models in mice. Cholesterol depletion decreased CHO cell viability. Sphingomyelinase and methyl-beta-cyclodextrin reduced the duration of icilin-evoked nocifensive behavior, while lipid raft disruptors did not inhibit the activity of recombinant TRPM3 and TRPM8. We conclude that depletion of sphingomyelin or cholesterol from rafts can modulate the function of native TRPM8 receptors. Furthermore, sphingolipid cleavage provided superiority over cholesterol depletion, and this method can open novel possibilities in the management of different pain conditions.

• Klíčová slova
• Transient Receptor Potential, cholesterol, lipid raft, methyl-beta-cyclodextrin, pain, sphingomyelinase,
• MeSH
• analgetika farmakologie   terapeutické užití   MeSH
• beta-cyklodextriny * farmakologie   MeSH
• bolest chemicky indukované   farmakoterapie   metabolismus   MeSH
• CHO buňky MeSH
• cholesterol metabolismus   MeSH
• Cricetulus MeSH
• HEK293 buňky MeSH
• kationtové kanály TRPM * metabolismus   genetika   MeSH
• lidé MeSH
• membránové mikrodomény metabolismus   účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• pregnenolon farmakologie   MeSH
• pyrimidinony farmakologie   MeSH
• sfingomyelinfosfodiesterasa * metabolismus   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• analgetika MeSH
• beta-cyklodextriny * MeSH
• cholesterol MeSH
• icilin MeSH Prohlížeč
• kationtové kanály TRPM * MeSH
• methyl-beta-cyclodextrin MeSH Prohlížeč
• pregnenolon MeSH
• pregnenolone sulfate MeSH Prohlížeč
• pyrimidinony MeSH
• sfingomyelinfosfodiesterasa * MeSH
• TRPM3 protein, mouse MeSH Prohlížeč
• TRPM8 protein, mouse MeSH Prohlížeč

Non-alcoholic fatty liver disease (NAFLD) is a general term for fatty liver disease not caused by viruses or alcohol. Fibrotic hepatitis, cirrhosis, and hepatocellular carcinoma can develop. The recent increase in NAFLD incidence worldwide has stimulated drug development efforts. However, there is still no approved treatment. This may be due in part to the fact that non-alcoholic steatohepatitis (NASH) pathogenesis is very complex, and its mechanisms are not well understood. Studies with animals are very important for understanding the pathogenesis. Due to the close association between the establishment of human NASH pathology and metabolic syndrome, several animal models have been reported, especially in the context of overnutrition. In this study, we investigated the induction of NASH-like pathology by enhancing cholesterol absorption through treatment with hydroxypropyl-beta-cyclodextrin (CDX). Female Sprague-Dawley rats were fed a normal diet with normal water (control group); a high-fat (60 kcal%), cholesterol (1.25 %), and cholic acid (0.5 %) diet with normal water (HFCC group); or HFCC diet with 2 % CDX water (HFCC+CDX group) for 16 weeks. Compared to the control group, the HFCC and HFCC+CDX groups showed increased blood levels of total cholesterol, aspartate aminotransferase, and alanine aminotransferase. At autopsy, parameters related to hepatic lipid synthesis, oxidative stress, inflammation, and fibrosis were elevated, suggesting the development of NAFLD/NASH. Elevated levels of endoplasmic reticulum stress-related genes were evident in the HFCC+CDX group. In the novel rat model, excessive cholesterol intake and accelerated absorption contributed to NAFLD/NASH pathogenesis.

• MeSH
• cholesterol MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• hydroxypropyl beta cyklodextrin metabolismus   terapeutické užití   MeSH
• hypercholesterolemie * metabolismus   MeSH
• hyperlipidemie * MeSH
• játra metabolismus   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• nealkoholová steatóza jater * chemicky indukované   MeSH
• potkani Sprague-Dawley MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholesterol MeSH
• hydroxypropyl beta cyklodextrin MeSH

Knowledge of mass transport parameters, diffusion, and viscosity of hyaluronic acid (HA) in the presence of cyclodextrins is of considerable importance for areas such as food packaging and drug delivery, among others. Despite a number of studies investigating the functionalization of HA or the corresponding sodium salt by cyclodextrins, only a few studies have reported the effect of cyclodextrins on the mass transport of HA in the presence of these oligosaccharides. Here, we report the tracer binary and ternary interdiffusion coefficients of sodium hyaluronate (NaHy) in water and aqueous β-cyclodextrin solutions. The diffusion behavior of sodium hyaluronate was dependent on the reduced viscosity of NaHy, which, in turn, presented a concave dependence on concentration, with a minimum at approximately 2.5 g dm-3. The significant decrease in the limiting diffusion coefficient of NaHy (at most 45%) at NaHy concentrations below 1 g dm-3 in the presence of β-cyclodextrin, taking water as the reference, allowed us to conclude that NaHy strongly interacted with the cyclodextrin.

• Klíčová slova
• diffusion, diffusion coefficients, salting-in, sodium hyaluronate, transport properties, viscosity, β-cyclodextrin,
• MeSH
• beta-cyklodextriny * MeSH
• cyklodextriny * MeSH
• difuze MeSH
• kyselina hyaluronová MeSH
• voda MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny * MeSH
• cyklodextriny * MeSH
• kyselina hyaluronová MeSH
• voda MeSH

Purine nucleosides represent an interesting group of nitrogen heterocycles, showing a wide range of biological effects. In this study, we designed and synthesized a series of 6,9-disubstituted and 2,6,9-trisubstituted purine ribonucleosides via consecutive nucleophilic aromatic substitution, glycosylation, and deprotection of the ribofuranose unit. We prepared eight new purine nucleosides bearing unique adamantylated aromatic amines at position 6. Additionally, the ability of the synthesized purine nucleosides to form stable host-guest complexes with β-cyclodextrin (β-CD) was confirmed using nuclear magnetic resonance (NMR) and mass spectrometry (ESI-MS) experiments. The in vitro antiproliferative activity of purine nucleosides and their equimolar mixtures with β-CD was tested against two types of human tumor cell line. Six adamantane-based purine nucleosides showed an antiproliferative activity in the micromolar range. Moreover, their effect was only slightly suppressed by the presence of β-CD, which was probably due to the competitive binding of the corresponding purine nucleoside inside the β-CD cavity.

• Klíčová slova
• adamantane, antiproliferative activity, glycosylation, nucleoside, purine, β-cyclodextrin,
• MeSH
• adamantan * farmakologie   MeSH
• beta-cyklodextriny * farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nukleosidy farmakologie   chemie   MeSH
• purinové nukleosidy farmakologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adamantan * MeSH
• beta-cyklodextriny * MeSH
• nukleosidy MeSH
• purinové nukleosidy MeSH

Chiral CE methods were developed for the elucidation of l- or d-configuration of tyrosine residue in antimicrobial dipeptide β-alanyl-tyrosine (β-Ala-Tyr) isolated from the hemolymph of larvae of fleshfly Neobellieria bullata and for the evaluation of enantiopurity of its synthetic isomers (β-Ala-d-Tyr and β-Ala-l-Tyr), and enantiomers of their amidated and acetylated derivatives, β-Ala-d,l-Tyr-NH2 and N-Ac-β-Ala-d,l-Tyr, respectively. Baseline separations were achieved for all three pairs of enantiomers: (i) for β-Ala-d,l-Tyr in acidic background electrolyte composed of 32/50 mM tris(hydroxymethyl)aminomethane/H3 PO4 , pH 2.5, and 20 mg/mL 2-hydroxypropyl-β-cyclodextrin as chiral selector; (ii) for β-Ala-d,l-Tyr-NH2 enantiomers in acidic background electrolyte consisting of 48/50 mM tris(hydroxymethyl)aminomethane/H3 PO4 , pH 3.5, and 30 mg/mL 2-hydroxypropyl-β-cyclodextrin; and (iii) for enantiomers of N-Ac-β-Ala-d,l-Tyr in alkaline background electrolyte composed of 50/49 mM Na2 B4 O7 /NaOH, pH 10.5, and 60 mg/mL 2-hydroxypropyl-β-cyclodextrin. From CE analyses of mixed samples of isolated β-Ala-Tyr and synthetic standards β-Ala-l-Tyr and β-Ala-d-Tyr, it turned out that isolated β-Ala-Tyr was pure l-enantiomer. In addition, the average apparent binding constants, Kb , and average actual ionic mobilities of the complexes of β-Ala-d,l-Tyr and its above derivatives with 2-hydroxypropyl-β-cyclodextrin were determined. These complexes were weak, with Kb values ranging from 11.2 to 79.1 L/mol. Their cationic mobilities were equal to (5.6-9.2) × 10-9 m2 /V/s, and anionic mobilities to (-1.3-1.6) × 10-9 m2 /V/s.

• Klíčová slova
• 2-hydroxypropyl-β-cyclodextrin, Binding constant, capillary electrophoresis, chiral separation, enantioseparation, β-alanyl-tyrosine,
• MeSH
• beta-cyklodextriny * chemie   MeSH
• cyklodextriny * chemie   MeSH
• elektroforéza kapilární metody   MeSH
• elektrolyty MeSH
• hydroxypropyl beta cyklodextrin MeSH
• koncentrace vodíkových iontů MeSH
• stereoizomerie MeSH
• tromethamin MeSH
• tyrosin MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny * MeSH
• cyklodextriny * MeSH
• elektrolyty MeSH
• hydroxypropyl beta cyklodextrin MeSH
• tromethamin MeSH
• tyrosin MeSH

Due to the increase in fungal resistance to existing drugs, a need exists to search for new antifungals. This study aimed to evaluate the antifungal activity of α, β, and δ-damascone and inclusion complexes with β-cyclodextrin against different Candida spp. The inclusion complex of β-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (βDA-βCD)) and analyzed using Fourier transform infrared spectroscopy (FTIR). Standard Candida albicans (CA INCQS 40,006), Candida krusei (CK INCQS 40,095), and Candida tropicalis (CT INCQS 40,042) strains were used to evaluate antifungal activity. The substances were tested individually or in association with fluconazole (FCZ). The IC50 and cell viability curve constructions were performed using the microdilution method. The minimum fungicidal concentration (MFC) was determined by the subculture method in a solid medium. The α, β, and δ-DA isolated or in combination with fluconazole (FCZ) showed significant antifungal activity. β-damascone showed effective complexation in the three molar proportions assayed; however, none of the inclusion complexes was demonstrated clinically significant effects against the fungal tested. Then, all compounds have shown promising antifungal activities; however, in vivo assays are necessary to have therapeutical application in the future.

• MeSH
• antifungální látky * chemie   farmakologie   MeSH
• beta-cyklodextriny * farmakologie   MeSH
• Candida MeSH
• flukonazol farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• norisoprenoidy farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antifungální látky * MeSH
• beta-cyklodextriny * MeSH
• flukonazol MeSH
• norisoprenoidy MeSH

It is pivotal to precisely detect food preservatives to ascertain food quality and safety. In this work, we report the sensitive electrochemical detection of widely used cytotoxic food preservative tert-butylhydroquinone (TBHQ). A novel nanocomposite was sonochemically prepared by embedding ternary metal oxide (TMO) comprising ZnO, CuO, and MgO in β-cyclodextrin (β-CD) functionalized carbon black (CB). The properties of the prepared nanocomposite were evaluated by employing multiple characterization methods. The nanocomposite fabricated on a screen printed carbon electrode exhibited exceptional electrocatalytic activity towards TBHQ detection, evident from the resultant very low detection limit of 1 nM and high sensitivity of 22.67 μA μM-1 cm-2. Moreover, the developed TBHQ sensor evinced all the important traits of a good electrochemical sensor including excellent selectivity, stability, reproducibility, and repeatability. Furthermore, for validating practical feasibility of TBHQ detection, we successfully determined this food additive in edible oils.

• Klíčová slova
• Cyclodextrin, Electrochemical sensor, Food preservative, TBHQ, Ternary metal oxide,
• MeSH
• beta-cyklodextriny * MeSH
• elektrochemické techniky MeSH
• elektrody MeSH
• hydrochinony MeSH
• oleje rostlin MeSH
• oxidy MeSH
• potravinářské přísady * MeSH
• reprodukovatelnost výsledků MeSH
• saze MeSH
• uhlík MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2-tert-butylhydroquinone MeSH Prohlížeč
• beta-cyklodextriny * MeSH
• hydrochinony MeSH
• oleje rostlin MeSH
• oxidy MeSH
• potravinářské přísady * MeSH
• saze MeSH
• uhlík MeSH

In this study, a sensitive platform was designed for the electrocatalytical oxidation and recognition of ascorbic acid (AA) based on poly(β-cyclodextrin) modified glassy carbon electrode (p(β-CD-GCE). Electropolymerization of β-CD on the surface of GCE was performed on the potential range of -1 to 1.5 V. So, a novel biopolymer was prepared on the surface of GCE towards sensitive recognition of AA in human plasma samples. The developed platform has good sensitivity and accuracy for electrooxidation and detection of AA with lower limit of quantification (LLOQ) of 1 nM and linear range of 1 nM to 100 mM. Moreover, the designed electrochemical sensor was employed for the analysis of AA on human plasma samples with high sensitivity. Based on advantages of p(β-CD) prepared by electropolymerization procedure (green, fast, homogeny, and efficient eletrocatalytical behaviour), this conductive biopolymer showed excellent analytical behaviour towards electrooxidation of AA. It is expected that the prepared polymeric interface is able to use in the analysis of biological species in clinical samples.

• Klíčová slova
• advanced biopolymer, biocompatible materials, electrochemical oxidation, electropolymerization, sensor technology, β-cyclodextrin,
• MeSH
• beta-cyklodextriny MeSH
• biokompatibilní materiály MeSH
• biopolymery MeSH
• elektrochemické techniky * metody   MeSH
• kyselina askorbová * MeSH
• lidé MeSH
• propylenglykoly MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny MeSH
• biokompatibilní materiály MeSH
• biopolymery MeSH
• kyselina askorbová * MeSH
• poly(beta-cyclodextrin) MeSH Prohlížeč
• propylenglykoly MeSH