quaternization
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BACKGROUND: Venotonics are a class of therapeutically active molecules that have vaso-protective effects. They are used to alleviate venous diseases and disorders, particularly venous insufficiency. We compared the composition of prescription versus over-the-counter (OTC) venotonics using high-performance liquid chromatography with UV detection (HPLC-DAD) and simulating their digestion using a static digestive model. METHODS: From each drug, five tablets were weighed. A homogenate was prepared, and 25 mg of crushed homogenized tablets were weighed into 25 ml volumetric flasks. Dissolved in MeOH and added two drops of saturated NaOH solution. The samples were filtered into vials (Teflon, 0.45 μm) and used for analysis. An Ultimate 3000 HPLC system (Thermo Fisher Scientific, Waltham, MA, USA) consisting of a quaternization pump, autosampler, column thermostat and DAD (UV/VIS detector) was used. The composition of the mobile phase proceeded in a linear gradient from 30% methanol and 70% phosphoric acid (0.15%) in water at time t=0 min. to 80% methanol and 20% phosphoric acid (0.15%) at time t=15 min., at a constant mobile phase flow rate of 1.2 mL/min. Detection was performed using a DAD detector in the 190-450 nm wavelength range. The content of monitored flavonoids was calculated from peaks at a wavelength of 277 nm, in which both flavonoids have their absorption maxima. The static digestive model was used to simulate the digestive phase from the oral cavity to the corresponding intestinal phase. RESULTS: The content of diosmin and hesperidin (mg per table) for a prescription drug: Detralex: 480 mg, 26 mg. The content of diosmin and hesperidin (mg per tablet) for OTC drugs: Venostop: 502 mg, 48 mg, Diosminol: 520 mg, 50 mg, Devenal: 496 mg, 49 mg, Diohes: 493 mg, 46 mg. Digestion did not affect the solubility of all tested drugs. The active substances could not be determined in the non-alkalized sample. After alkalization, part of the insoluble matter was visibly dissolved and converted to a yellow flavonoid complex. Neither diosmin nor hesperidin could be identified afterwards. CONCLUSIONS: Our experimental results show that the contents of both listed active substances, diosmin and hesperidin, met the declared amounts in all tested medicaments. Digestion simulation showed identical behaviour in prescription and OTC venotonics. The active substances could not be determined in the non-alkalized sample. Digestion did not affect the solubility of the tested drugs.
Stimuli-responsive copolymers are of great interest for targeted drug delivery. This study reports on a controllable post-polymerization quaternization with 2-bromomethyl-4-fluorophenylboronic acid of the poly(4-vinyl pyridine) (P4VP) block of a common poly(styrene)-b-poly(4-vinyl pyridine)-b-poly(ethylene oxide) (SVE) triblock terpolymer in order to achieve a selective responsivity to various diols. For this purpose, a reproducible method was established for P4VP block quaternization at a defined ratio, confirming the reaction yield by 11B, 1H NMR. Then, a reproducible self-assembly protocol is designed for preparing stable micelles from functionalized stimuli-responsive triblock terpolymers, which are characterized by light scattering and by cryogenic transmission electron microscopy. In addition, UV-Vis spectroscopy is used to monitor the boron-ester bonding and hydrolysis with alizarin as a model drug and to study encapsulation and release of this drug, induced by sensing with three geminal diols: fructose, galactose and ascorbic acid. The obtained results show that only the latter, with the vicinal diol group on sp2-hybridized carbons, was efficient for alizarin release. Therefore, the post-polymerization method for triblock terpolymer functionalization presented in this study allows for preparation of specific stimuli-responsive systems with a high potential for targeted drug delivery, especially for cancer treatment.
- Publikační typ
- časopisecké články MeSH
Photodynamic therapy is a treatment modality of cancer based on the production of cytotoxic species upon the light activation of photosensitizers. Zinc phthalocyanine photosensitizers bearing four or eight bulky 2,6-di(pyridin-3-yl)phenoxy substituents were synthesized, and pyridyl moieties were methylated. The quaternized derivatives did not aggregate at all in water and retained their good photophysical properties. High photodynamic activity of these phthalocyanines was demonstrated on HeLa, MCF-7, and EA.hy926 cells with a very low EC50 of 50 nM (for the MCF-7 cell line) upon light activation while maintaining low toxicity in the dark (TC50 ≈ 600 μM), giving thus good phototherapeutic indexes (TC50/EC50) above 1400. The compounds localized primarily in the lysosomes, leading to their rupture after light activation. This induced an apoptotic cell death pathway with secondary necrosis because of extensive and swift damage to the cells. This work demonstrates the importance of a bulky and rigid arrangement of peripheral substituents in the development of photosensitizers.
- Publikační typ
- časopisecké články MeSH
High photodynamic activity was observed for hexadeca-cationic zinc, magnesium, and metal-free phthalocyanines (Pcs) and tetrapyrazinoporphyrazines with EC50 values as low as 5 nM (MCF-7 cells) for the best compound; this activity was several times better than that of clinically established photosensitizers verteporfin, temoporfin, S3AlOHPc, or protoporphyrin IX. This lead compound was characterized by low dark toxicity (TC50 = 369 μM), high efficiency against other cell lines (HCT 116 and HeLa), and possible activation by light above 680 nm. The excellent photodynamic activity resulted from the rigid spatial arrangement of the quaternized triazole moieties above and below the Pc core, as confirmed by X-ray crystallography. The triazole moieties thus formed two "cationic donuts" that protected the hydrophobic core against aggregation in water. The lysosomes were found to be the site of subcellular localization and were consequently the primary targets of photodynamic injury, resulting in predominantly necrotic cell death.
- MeSH
- fotochemoterapie MeSH
- fotosenzibilizující látky chemická syntéza chemie farmakologie MeSH
- indoly chemická syntéza chemie farmakologie MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- lyzozomy metabolismus MeSH
- molekulární konformace MeSH
- nádorové buněčné linie MeSH
- nekróza MeSH
- porfyriny chemická syntéza chemie farmakologie MeSH
- pyrazoly chemická syntéza chemie farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- triazoly chemická syntéza chemie farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A new ion-exchanger type chiral stationary phase for high-performance liquid chromatography was prepared. The synthetic protocol is based on derivatization of silica with (3-iodopropyl)trimethoxysilane in the first step followed by immobilization of strychnine via quaternization of nitrogen atom of the alkaloid strychnine. The synthesized chiral stationary phase was chromatographically characterized. The main effort was headed towards the evaluation of the enantioselectivity of the novel sorbent. For that purpose a set of suitable chiral probes, specifically, binaphthyl derivatives, was employed. The influence of methanol content, concentration of aqueous ammonium acetate buffer, and its pH on retention factors, separation selectivity, and resolution of the atropoisomers of the mentioned chiral solutes was studied in detail. It was demonstrated that the new chiral stationary phase was capable to separate atropoisomers of four out of seven testing compounds. Despite the strong influence of the above mentioned variables on retention, their impact on selectivity and resolution was rather moderate. Concerning retention mechanism, it seems that electrostatic interaction between the positively charged quaternary nitrogen of the chiral stationary phase and anionic solute participates significantly in the retention process.
Understanding the behavior of single proteins at the polyelectrolyte multilayer film/solution interface is of prime importance for the designing of bio-functionalized surface coatings. In the present paper, we study the adsorption of the model proteins, albumin and lysozyme, as well as basic fibroblast growth factor (FGF-2) on a polysaccharide multilayer film composed of quaternized chitosan and heparin. Several analytical methods were used to describe the formation of the polysaccharide film and its interactions with the proteins. Both albumin and lysozyme adsorbed on quaternized chitosan/heparin films, however this process strongly depended on the terminating polysaccharide. Protein adsorption was driven mainly by electrostatic interactions between protein and the terminal layer of the film. The effective binding of FGF-2 by the heparin-terminated film suggested that other interactions could also contribute to the adsorption process. We believe that this FGF-2-presenting polysaccharide film may serve as a biofunctional surface coating for biologically-related applications.
Cationic quaternized carbon dots (QCDs) and anionic graphene oxide sheets (GO) are combined via non-covalent interactions following a self-assembly pathway to form highly biocompatible and fluorescent hybrid materials. These hybrids act as selective probes with controlled labelling of the cell nucleus or cytoplasm depending on the QCD loading.
- MeSH
- buněčné jádro chemie metabolismus MeSH
- buňky NIH 3T3 MeSH
- cytoplazma chemie metabolismus MeSH
- grafit chemie MeSH
- kationty chemie MeSH
- konfokální mikroskopie MeSH
- kvantové tečky chemie metabolismus MeSH
- myši MeSH
- oxidy chemie MeSH
- uhlík chemie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
New 2-amino-3-cyanopyrrole derivatives were prepared and converted to 7-deazapurines. 7-Deazaadenine 6 was synthesized by different methods and alkylated with alkyl iodides to afford the quaternized 3-alkylpyrrolopyrimidinium iodide salts 8. The latter salts were dequaternized to N-alkylpyrrolo[2,3-d]pyrimidin-4-amines 12. Compounds 12 were identical to the products obtained from reactions of 4-chloro-7-(4-fluorophenyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidine 11 with methyl- or ethylamine in the presence of a catalyst. The thione 13 and its related 4-methylthio- and 4-ylcarbonothioate derivatives 14a, 14b were obtained. The triazolo- 17a–17e, benzenesulfonamido- 19, and tetrazolopyrrolopyrimidine 21 derivatives were synthesized. Several examples of the synthesized pyrrole- and pyrrolo[2,3-d]pyrimidine derivatives showed high to remarkable antioxidant scavenging activity as measured by their ability to scavenge the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical
