Browsing by Author "Georgieva M."
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Item Amination of graphene oxide leads to increased cytotoxicity in hepatocellular carcinoma cells(2020-04-01) Georgieva M.; Vasileva B.; Speranza G.; Wang D.; Stoyanov K.; Draganova-Filipova M.; Zagorchev P.; Sarafian V.; Miloshev G.; Krasteva N.Clinically, there is an urgent need to identify new therapeutic strategies for selectively treating cancer cells. One of the directions in this research is the development of biocompatible therapeutics that selectively target cancer cells. Here, we show that novel aminated graphene oxide (haGO-NH2) nanoparticles demonstrate increased toxicity towards human hepatocellular cancer cells compared to pristine graphene oxide(GO). The applied novel strategy for amination leads to a decrease in the size of haGO-NH2 and their zeta potential, thus, assuring easier penetration through the cell membrane. After characterization of the biological activities of pristine and aminated GO, we have demonstrated strong cytotoxicity of haGO-NH2 toward hepatic cancer cells-HepG2 cell line, in a dose-dependent manner. We have presented evidence that the cytotoxic effects of haGO-NH2 on hepatic cancer cells were due to cell membrane damage, mitochondrial dysfunction and increased reactive oxygen species (ROS) production. Intrinsically, our current study provides new rationale for exploiting aminated graphene oxide as an anticancer therapeutic.Item Analgesic properties of newly synthesized N-pyrrolyl hydrazide hydrazones(2023-01-01) Nocheva H.; Vladimirova S.; Tzankova D.; Peikova L.; Georgieva M.Purpose: To screen a series of newly synthesized N-pyrrolyl hydrazide hydrazones for analgesic activity via Paw-pressure (PP) test and hot plate test (HPT). Methods: The compounds newly synthesized through the classical Paal-Knor cyclization, N-pyrrolyl hydrazide-hydrazones were administered intraperitoneally at a dose of 20 mg/kg. Paw pressure and hot plate tests were applied to assess the analgesic properties. In addition, stress-induced analgesia with naloxone as a non-selective opioid receptor antagonist was performed. Results: The compound (DI-5g), containing an izatine carbonyl fragment, was the most promising. It presented the highest paw pressure threshold (25 AU at 30th min) by exceeding the analgesic activity of the referent metamizole (23 AU at 30th min). The relative effect from the hot plate test was consistent with the paw pressure results. Opioid receptors were involved in the analgesic activities of N-pyrrolyl hydrazide-hydrazones. Conclusion: The N-pyrrolyl carboxylic acids are synthesized and identified as new compounds and their hydrazide-hydrazone derivatives as promising leads for future design and synthesis of drugs with possibly prolonged analgesic activity.Item Development and validation of an RP-HPLC method for analysis of 2-(5-(4-chlorophenyl)-3-(ethoxycarbonyl)-2-methyl-1H-pyrrol-1-yl)propanoic acid and its impurities under different pH(2022-01-01) Maslarska V.; Bozhanov S.; Vladimirova S.; Peikova L.; Tzankova D.; Georgieva M.A simple, fast and selective stability indicating RP-HPLC method was applied for following the degradation and appearance of impurities of previously synthesized 2-(5-(4-chlorophenyl)-3-(ethoxycarbonyl)-2-methyl-1H-pyrrol-1-yl)propanoic acid. The chromatographic separation was achieved on a C18 column (150x4 mm i.d., 5 µm) using a mobile phase consisting of Acetonitrile: Phosphate buffer, pH=3, (50:50% v/v) with isocratic elution at a flow rate of 1.0 mL min-1 and temperature of the column of 30 °C applying a UV/VIS detector at 225 nm. The method was validated according to the ICH guidelines. A process related impurity was determined at pH 9.0 corresponding to ethyl 2-acetyl-4-(4-chlorophenyl)-4-oxobutanoate. No change in the structure was detected at pH = 7.4.Item Development and validation of RP-HPLC method for stability evaluation of model hydrazone, containing a pyrrole ring(2019-01-01) Tzankova D.; Peikova L.; Vladimirova S.; Georgieva M.RP-HPLC method with UV detection was developed and validated for determination of the chemical stability and stability in close to physiological conditions of a model pyrrole hydrazone ethyl 5-(4-bromophenyl)-1-(1-(2-(4-hydroxy-3-methoxybenzylidene) hydrazineyl)-4-methyl-1-oxopentan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate (D_5d), containing susceptible to hydrolysis hydrazone group. The evaluated substance was subjected to the influence of a variety of pH, representing the main physiological values of 37°C and corresponding pH values in the stomach (pH 2.0), blood (pH 7.4) and small intestine (pH 9.0). Chemical stability in a highly alkaline medium with a pH of 13.0 was also evaluated. The hydrazone I tested was found to be stable at pH 7.4 and pH 9.0 and 37 ° C and hydrolyzed under strong acidic (pH 2.0) and highly alkaline media (pH 13.0) and at the same temperature.The products of hydrolysis were identified to be the initial hydrazide and aldehyde, pointing the hydrazone group as most liable.Item EVALUATION OF THE IN VITRO NEUROTOXIC AND NEUROPROTECTIVE EFFECTS AT CELLULAR AND SUBCELLULAR LEVELS OF NEWLY SYNTHESIZED N-PYRROLYL HYDRAZONES(2022-01-01) Tzankova D.; Vladimirova S.; Stefanova D.; Peikova L.; Kondeva-Burdina M.; Georgieva M.The study presents the safety, antioxidant activity and neuroprotective effects of a series of newly synthesized N-pyrrolyl hydrazide-hydrazones (5, 5a-g) in two in vitro models: human neuronal cells SH-SY5Y and isolated rat brain synaptosomes. The performed in vitro toxicological evaluation in neuronal SH-SY5Y cell line models determined the lowest cytotoxicity and best safety profile for compound 5a, followed by 5d on both evaluated parameters. The protective effect of the newly synthesized hydrazone 5a was found to be comparable to melatonin used as a standard. The obtained results indicate that the presence of pyrrole ring, containing multiple phenyl nuclei and hydrazide-hydrazone group in the side chain, leads to increase in the antioxidant effect.Item Glass–crystalline materials with high iron oxide concentration: Phase composition, redox ratio and magnetic properties Vitrocerámicas con alta concentración de óxido de hierro: Composición de fases, relación redox y propiedades magnéticas(2024-01-01) Harizanova R.; Mihailova I.; Cherkezova-Zheleva Z.; Paneva D.; Georgieva M.; Tzankov D.; Avdeev G.; Rüssel C.The synthesis of glass–crystalline materials in the system Na2O/CaO/SiO2/Fe2O3 with high concentrations of Fe2O3 (20, 25 and 30 mol%) by applying the melt-quenching technique is reported. The melts spontaneously crystallize during pouring and the formation of magnetite (Fe3O4), hematite (α-Fe2O3) and ɛ-Fe2O3, as identified by X-ray diffraction (XRD) is observed. The microstructure and the elemental composition of the prepared materials are further investigated by scanning electron microscopy (SEM) and two different morphological types of Fe-containing crystals – needle-like and dendrite-shaped are detected. Mössbauer spectroscopy showed the presence of Fe3+ and Fe2+, as well as the existence of iron ions both in tetrahedral and octahedral coordination and the precipitation of hematite, ɛ-Fe2O3 and magnetite. The magnetic measurements on the prepared samples reveal ferrimagnetic properties with well defined hysteresis curves, although due to relatively small volume fraction of the iron-rich crystalline phases, the net magnetic moment is quite low compared to the bulk values for magnetite.Item INFLUENCE OF THE FINAL THERMAL SEALING ON THE PROPERTIES OF COMBINED ANODIC ALUMINA/CERIUM CONVERSION COATINGS ON AA2024-T3 AIRCRAFT ALLOY(2023-01-01) Girginov C.; Kozhukharov S.; Tsanev A.; Georgieva M.; Petrova M.; Lilov E.; Petkov P.The current research presents results following corrosion tests, performed on combined anodic alumina/cerium conversion coatings (Al2O3/CeCC), thermally sealed for 15 min at 100°C either in boiling water or in hot-air medium. The coatings were formed on AA2024-T3 aircraft alloy substrates, at the optimum conditions of anodization and cerium conversion coating deposition, described in previous works. Prior to the corrosion tests, both the color characteristics and wetting ability of the combined films were evaluated. The corrosion protective properties of the sealed films were assessed by means of Electrochemical Impedance Spectroscopy (EIS) and Potentiodynamic Polarization (PDP). The measurements were performed after 672 hours of exposure to a 5 % NaCl model corrosive medium (MCM). Additional long term (up to 1344 hours of exposure) durability tests were then performed under the same conditions for the samples and superior performance was established. The electrochemical measurements were conducted regularly, once a week. Low and high-resolution Scanning Electron Microscopy (SEM) studies were performed on selected samples. The experimental results have shown that the sealing procedure in an aqueous environment enhances the corrosion protective ability and durability of the coating, probably due to formation of a hydrate layers, that suppresses the access of corrosive species to the surface of the substrate. This inference was additionally confirmed by the subsequent chemical analysis by means of X-Ray Photoelectron Spectroscopy (XPS). The results acquired have also shown that the incorporated Ce is predominantly in the form of Ce(IV)-oxides/hydroxides and after the thermal treatment almost entirely consists of cerium.Item Synthesis of pyrrole and substituted pyrroles (Review)(2018-01-01) Tzankova D.; Vladimirova S.; Peikova L.; Georgieva M.Pyrrole is widely known as a biologically active scaffold which possesses a diverse nature of activities. The combination of different pharmacophores in a pyrrole ring system has led to the formation of more active compounds. Pyrrole containing analogs are considered as a potential source of biologically active compounds that contains a significant set of advantageous properties and can be found in many natural products. The present review highlights the synthetic methods of representatives of nitrogen heterocycles such as pyrrole, substituted pyrroles and other related compounds. The aim of this review is to indicate and summarise the different methods for the synthesis of nitrogen containing heterocycles from the group of pyrrole and pyrrole related structures.Item Synthesis, in vitro safety and antioxidant activity of new pyrrole hydrazones(2020-09-01) Tzankova D.; Vladimirova S.; Aluani D.; Yordanov Y.; Peikova L.; Georgieva M.Six new N-pyrrolylhydrazide hydrazones were synthesized under micro synthesis conditions, assuring about 59-93 % yield, low harmful emissions and reagent economy. The structures of the new compounds were elucidated by melting points, TLC characteristics, IR, 1H and 13C NMR spectral data followed by MS data. The purity of the obtained compounds was proven by the corresponding elemental analyses. ``Lipinski's rule of five`` parameters were applied for preliminary evaluation of the pharmacokinetic properties of the target molecules. The initial in vitro safety screening for cytotoxicity (on HepG2 cells) and hemocompatibility (hemolysis assay) showed good safety of the new compounds, where ethyl 5-(4-bromophenyl)-1-(1-(2-(4-hydroxy-3-methoxybenzylidene)-hydrazineyl)-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyr-role-3-carboxylate (4d) and ethyl 5-(4-bromophenyl)-1-(1-(2-(2-hydroxybenzylidene)hydrazineyl)-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate (4a) were the least toxic. The antioxidant activity in terms of radical scavenging activity (DPPH test) and reducing ability (ABTS) was also evaluated. The antioxidant protective potential of the compounds was next determined in different in vitro cellular-based models, revealing compounds 4d and 3 [ethyl 5-(4-bromophenyl)-1-(1-hydrazineyl-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate] as the most promising compounds, with 4d having better safety profile.