Browsing by Author "Tzankova D."

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    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.
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    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.
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    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.
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    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.
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    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.
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    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.