In the present study, the primary action of native cyclodextrins (CDs) on lysozyme protein as binding ligand and secondary as aggregation inhibitor were probed. Thermally induced denaturation using differential scanning calorimetry (DSC) was measured in the presence of native α-, β- and γ-CDs. The denaturation process in CD absence was reversible to 60-80 % at pH≤6 with maximum Tm at pH=4. Denaturation in the presence of native α-CD at pH from 2 to 10, at the least stable and partially reversible conditions in presence of β-CD and γ-CDs at single pH 2 only, was measured. The protein thermal stability decreases in the presence of CDs, with the most evident for β-CD, followed by α-CD and almost no effect for γ-CD. The reversibility in the presence of α-CD was similar to that in its absence. The best protection performance against heat-induced denaturation was found at pH 2 for β-CD. The heat capacity data for α-CD at acidic pH were fitted by the protein-ligand binding model in the whole temperature and ligand concentration ranges studied. The decrease in thermal stability for α-CD at all pH, β- and γ-CD at pH 2 were fitted linearly as a function of ligand concentration. The CD-to-lysozyme binding parameters obtained in this work and from the literature for other CDs are briefly discussed using the concept of cyclodextrin cavity size, charge distribution, solvent accessible surface area and amino acid hydrophobicity.

• Klíčová slova
• Cyclodextrin, Differential scanning calorimetry, Inclusion complex lysozyme binding model,
• MeSH
• cyklodextriny * chemie   farmakologie   MeSH
• denaturace proteinů MeSH
• diferenciální skenovací kalorimetrie MeSH
• koncentrace vodíkových iontů MeSH
• kur domácí MeSH
• muramidasa * chemie   metabolismus   MeSH
• stabilita enzymů účinky léků   MeSH
• teplota * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklodextriny * MeSH
• muramidasa * MeSH

Sulfated cyclodextrins (CDs) are multiply negatively charged molecules widely used as chiral selectors in capillary electrophoresis (CE). In some of their applications, the effective charge numbers of their molecules were observed to be lower than the numbers of the attached sulfated groups due to strong binding of counterions. However, degree of reduction of the theoretical charge was not quantified. For that reason, in this study, capillary isotachophoresis (CITP) and capillary zone electrophoresis (CZE) were applied for the determination of the effective charge numbers and actual ionic mobilities of two kinds of sulfated CDs: single isomer sulfated α-, β-, and γ-CDs (SI-CDs) and randomly highly sulfated α-, β-, and γ-CDs (HS-CDs). The effective charge numbers of the SI-CDs and HS-CDs were determined from the length of their ITP zones, the ionic mobilities determined by CZE, and molar concentrations of their solutions applied for CITP analysis, and from the same parameters of reference compounds, formic acid for SI-CDs and dichloroacetic acid for HS-CDs. The determined effective charge numbers of the SI-CDs were equal to or only slightly lower than the numbers of sulfate groups in their molecules but the effective charge numbers of randomly HS-CDs were significantly (22.2%-27.8%) reduced as compared to the average numbers of sulfate groups in their molecules. In accordance with a lower number of sulfate groups in SI-CDs than in HS-CDs, the absolute values of the actual ionic mobilities of SI-CDs (35.5-37.5) × 10-9 m2 V-1 s-1 were lower than those of HS-CDs (43.5-44.1) × 10-9 m2 V-1 s-1.

• Klíčová slova
• capillary isotachophoresis, capillary zone electrophoresis, charge number, counterion condensation, effective charge,
• MeSH
• cyklodextriny * chemie   analýza   MeSH
• elektroforéza kapilární metody   MeSH
• isomerie MeSH
• izotachoforéza * metody   MeSH
• sírany * chemie   MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklodextriny * MeSH
• sírany * MeSH

The stability of collagen, the most abundant protein in humans and many animals, is related to the hydroxylation of L-proline, a post-translational modification occurring at carbon 3 and 4 on its pyrrolidine ring. Collagens of different origins have shown different proline hydroxylation levels, making hydroxyprolines useful biomarkers in structure characterizations. The presence of two chiral carbon atoms, 3-hydroxyproline and 4-hydroxyproline, results in eight stereoisomers (four pairs of enantiomers) whose quantitation in collagen hydrolysates requires enantioselective analytical methods. Capillary electrophoresis was applied for the separation and quantitation of the eight stereoisomers of 3- and 4-hydroxyproline and D,L-proline in collagen hydrolysates. The developed method is based on the derivatization with the chiral reagent (R)-(-)-4-(3-Isothiocyanatopyrrolidin-yl)-7-nitro-2,1,3-benzoxadiazole, enabling the use of a light-emitting diode-induced fluorescence detector for high sensitivity. The separation of the considered compounds was accomplished in less than 10 min, using a 500 mM acetate buffer pH 3.5 supplemented with 5 mM of heptakis(2,6-di-O-methyl)-β-cyclodextrin as the chiral selector. The method was fully validated and showed the adequate sensitivity for the application to samples of collagen hydrolysates. The analysis of samples extracted from chicken Pectoralis major muscles affected by growth-related myopathies showed different stereoisomer patterns compared to those from the unaffected control samples.

• Klíčová slova
• capillary electrophoresis, chiral separations, collagen, cyclodextrins, derivatization, fast-growing chickens, fluorescent detection, hydroxyprolines, spaghetti meat, wooden breast,
• MeSH
• cyklodextriny * chemie   MeSH
• elektroforéza kapilární metody   MeSH
• hydroxyprolin * chemie   analýza   MeSH
• kolagen * chemie   MeSH
• kur domácí MeSH
• prolin * chemie   analýza   MeSH
• proteinové hydrolyzáty * chemie   MeSH
• stereoizomerie MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklodextriny * MeSH
• hydroxyprolin * MeSH
• kolagen * MeSH
• prolin * MeSH
• proteinové hydrolyzáty * MeSH

Ruthenium(III) complexes are promising anticancer metallodrugs because of their antimetastatic (migrastatic) potential and significantly lower host toxicity than generally used platinum metallodrugs. On the other hand, the ruthenium(III) complexes generally show low solubility and stability in an aqueous environment but exhibit some toxicity associated with unspecific delivery. For these reasons, numerous ongoing studies deal with their encapsulation into various delivery systems to maximize their therapeutic efficacy. One of these systems can also be crystals of nontoxic metal-organic frameworks (MOFs). In this work, we studied incorporation of a bioactive ruthenium(III) complex (RuC) inside MOFs derived from γ-cyclodextrin (γ-CD) and biocompatible potassium ions, forming CD-MOF-1. Viability studies in vitro were carried out using spheroids of human hepatoblastoma cell line HepG2. These studies revealed that the RuC-CD-MOF-1 system provides effective cancer cell suppression through slow gradual release over a longer period (>10 days) while reducing acute cytotoxic effects associated with naked RuC. This combination was defined for further development and optimization as a drug-delivery platform for metallodrugs.

• MeSH
• buňky Hep G2 MeSH
• cyklodextriny * chemie   MeSH
• gama-cyklodextriny * chemie   MeSH
• komplexní sloučeniny * chemie   farmakologie   chemická syntéza   MeSH
• lidé MeSH
• molekulární struktura MeSH
• porézní koordinační polymery * chemie   farmakologie   chemická syntéza   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky * farmakologie   chemie   chemická syntéza   MeSH
• ruthenium * chemie   farmakologie   MeSH
• screeningové testy protinádorových léčiv MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklodextriny * MeSH
• gama-cyklodextriny * MeSH
• komplexní sloučeniny * MeSH
• porézní koordinační polymery * MeSH
• protinádorové látky * MeSH
• ruthenium * MeSH

Cholesterol, the essential building block of cellular membranes, has proven to be a useful tool for increasing the biocompatibility and bioavailability of drug delivery systems in cancer treatment. Resveratrol, a natural polyphenolic compound with promising anticancer properties, faces significant limitations due to its low solubility and bioavailability, hindering its clinical utility. Therefore, in the present study, we aimed to design cholesterol-functionalized cyclodextrin nanosponges (Chol-NSs) with a tunable cholesterol content to optimize resveratrol encapsulation and delivery. Both formulations, free carbonyl diimidazole (CDI) NSs and functionalized Chol-NSs, demonstrated high drug loading and encapsulation efficiency. In vitro experiments revealed that cholesterol incorporation significantly improved the cellular uptake of nanocarriers and potentiated the cytotoxic effects of resveratrol on breast cancer cells. Importantly, both free CDI NSs and functionalized Chol-NSs, even at varying cholesterol percentages, demonstrated a safe profile against both fibroblast and breast cancer cell lines. These results indicate that cholesterol-functionalized nanosponges represent a promising platform for the effective and safe delivery of natural compounds in cancer therapy.

• Klíčová slova
• cholesterol, crosslinked polymer, drug delivery, functionalization, nanosponge,
• MeSH
• biologická dostupnost MeSH
• buňky 3T3 MeSH
• cholesterol * chemie   MeSH
• cyklodextriny * chemie   MeSH
• imidazoly chemie   MeSH
• lékové transportní systémy * metody   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• myši MeSH
• nádory prsu * farmakoterapie   patologie   MeSH
• nanostruktury * chemie   MeSH
• příprava léků metody   MeSH
• protinádorové látky aplikace a dávkování   farmakokinetika   MeSH
• resveratrol * aplikace a dávkování   farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholesterol * MeSH
• cyklodextriny * MeSH
• imidazoly MeSH
• N,N-carbonyldiimidazole MeSH Prohlížeč
• protinádorové látky MeSH
• resveratrol * MeSH

Sugammadex (SGM) is the first cyclodextrin (CD)-based selective relaxant binding agent. We investigated its ability to capture natural aminosteroid phytotoxins, and assessed its potential as an antidote for intoxication. Solasodine (SS), a toxic alkaloid from the Solanaceae family, was chosen as the model compound. Complexation was studied using nuclear magnetic resonance (NMR) spectroscopy, molecular modelling, and isothermal titration calorimetry (ITC). NMR in various D2O/DMSO‑d6 media revealed a particularly stable inclusion-type complex, identifying a slow exchange process between the CD and the aminosteroid along with a less significant fast exchange between DMSO and SGM. Using various NMR techniques, the structure and kinetic/thermodynamic parameters of the inclusion complex were explored. Theoretical calculations showed the secondary amino head of SS near the carboxylate ends of the SGM sidechains, facilitating intermolecular ionic interactions. ITC experiments in an aqueous environment provided Ka stability constants of 7.03 × 106 M-1 and 4.17 × 106 M-1 at 25 °C and 37 °C, respectively, similar to previously reported SGM complexes with aminosteroid neuromuscular blockers. Finally, SGM significantly increased cell survival and reduced SS toxicity in mHippoE-14 mouse hippocampal embryonic cells, supporting the hypothesis that SGM could act as an antidote to SS's toxic effects.

• Klíčová slova
• Antidote, Competitive titration, ITC, NMR spectroscopy, Solasodine, Sugammadex,
• MeSH
• alkaloidy Solanaceí * chemie   farmakologie   MeSH
• buněčné linie MeSH
• hipokampus účinky léků   MeSH
• molekulární modely MeSH
• myši MeSH
• sugammadex * chemie   farmakologie   MeSH
• termodynamika MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaloidy Solanaceí * MeSH
• solasodine MeSH Prohlížeč
• sugammadex * MeSH

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 growing consumption of drugs of abuse together with the inefficiency of the current wastewater treatment plants toward their presence has resulted in an emergent class of pollutants. Thus, the development of alternative approaches to remediate this environmental threat is urgently needed. Microrobots, combining autonomous motion with great tunability for the development of specific tasks, have turned into promising candidates to take on the challenge. Here, hybrid urchin-like hematite (α-Fe2O3) microparticles carrying magnetite (Fe3O4) nanoparticles and surface functionalization with organic β-cyclodextrin (CD) molecules are prepared with the aim of on-the-fly encapsulation of illicit drugs into the linked CD cavities of moving microrobots. The resulting mag-CD microrobots are tested against methamphetamine (MA), proving their ability for the removal of this psychoactive substance. A dramatically enhanced capture of MA from water with active magnetically powered microrobots when compared with static passive CD-modified particles is demonstrated. This work shows the advantages of enhanced mass transfer provided by the externally controlled magnetic navigation in microrobots that together with the versatility of their design is an efficient strategy to clean polluted waters.

• Klíčová slova
• illicit drugs, iron oxides, magnetic actuation, water remediation,
• MeSH
• chemické látky znečišťující vodu * chemie   izolace a purifikace   MeSH
• čištění vody metody   MeSH
• cyklodextriny * chemie   MeSH
• magnetismus MeSH
• methamfetamin * chemie   MeSH
• robotika MeSH
• železité sloučeniny chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemické látky znečišťující vodu * MeSH
• cyklodextriny * MeSH
• ferric oxide MeSH Prohlížeč
• methamfetamin * MeSH
• železité sloučeniny 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

Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a Lipodex™ D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-β-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA-derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G-PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively.

• Klíčová slova
• GC, MS, NPS, benzofurans, benzofurys, chiral, cyclodextrin, designer drugs, novel psychoactive substances,
• MeSH
• amfetaminy * chemie   izolace a purifikace   MeSH
• chromatografie plynová metody   MeSH
• cyklodextriny chemie   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí metody   MeSH
• stereoizomerie MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amfetaminy * MeSH
• cyklodextriny MeSH