Stanislava Vladimirova - Academia.edu (original) (raw)
Uploads
Papers by Stanislava Vladimirova
![Research paper thumbnail of In Vivo Evaluation of Anti-inflammatory Activity of 2-[3-Acetyl- 5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-4-methylsulfanylbutyric Acid](https://attachments.academia-assets.com/114249804/thumbnails/1.jpg)
](Folia Medica, Jun 1, 2018
Acta Pharmaceutica, Feb 17, 2020
, in vitro safety and antioxidant activity of new pyrrole hydrazones Six new N-pyrrolylhydrazide ... more , in vitro safety and antioxidant activity of new pyrrole hydrazones 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, 1 H and 13 C 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-pyrrole-3-carboxylate (4d) and ethyl 5-(4-bromophenyl)-1-(1-(2-(2hydroxybenzylidene)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.
Heterocyclic Communications, Mar 31, 2014
Twenty new N-pyrrolylcarboxylic acids were designed to assume the architecture of contemporary se... more Twenty new N-pyrrolylcarboxylic acids were designed to assume the architecture of contemporary selective COX-2 inhibitors as potential anti-inflammatory agents. The targeted products were synthesized in 70-82% yields by Paal-Knorr cyclization of a set of eight amino acids, acting as primary amines, and four 1,4-dicarbonyl compounds. The latter substrates were prepared by C-alkylation of three commercially available β-dicarbonyl compounds with two ω-bromoacetophenones and used in situ. These compounds inhibit carrageenin-induced rat paw edema and show analgesic activity.
Tropical Journal of Pharmaceutical Research, Feb 18, 2023
Purpose: To screen a series of newly synthesized N-pyrrolyl hydrazide hydrazones for analgesic ac... more 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.
European Neuropsychopharmacology, 2019
Protein and Peptide Letters, Sep 1, 2007
Фармация, Apr 5, 2022
Development and validation of an RP-HPLC method for analysis of 2-(5-(4-chlorophenyl)-3-(ethoxyca... more 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.
Pharmaceutical Chemistry Journal, 2022
Two new N-pyrrolylcarboxylic acids were synthesized via Paal-Knorr cyclization by condensation of... more Two new N-pyrrolylcarboxylic acids were synthesized via Paal-Knorr cyclization by condensation of γ-aminobutyric acid and 1,4-dicarbonyl compounds. The obtained structures were elucidated by IR and 1 H-NMR spectral data and their purity was proven by TLC characteristics and melting points. The corresponding phytochemical activity of the obtained compounds on wheat and cucumber cultivars in three concentrations was studied. Both molecules were tested at 4 concentrations for herbicidal activity whereat no concentration dependence of the herbicidal effects was established. The inhibition of growth of the aerial parts and roots at the lowest (0.001 mM) and the highest (1 mM) concentration of the compounds was comparable. In addition a number of structural parameters were calculated for the target compounds and some analogues thereof. A second degree polynomial structure-activity dependency on the herbicidal effects from the corresponding miLogP was observed with R 2 in the range of 0.79...
Pyrrole is widely known as a biologically active scaffold which possesses a diverse nature of act... more 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.
Pharmacology, Drug Development & Therapeutics, 2016
This paper proposes a simple and selective UHPLC method for determination of degradation products... more This paper proposes a simple and selective UHPLC method for determination of degradation products of a model pyrrole based compound, containing susceptible to hydrolysis ester group. The chromatographic separation was achieved on BDSHYPERSILC18 (150 mm × 4.6 mm, 3.5 μm) column thermostated at 30°C under gradient elution by a binary mixture of potassium dihydrogen phosphate (pH 3.0, 0.02 M) and acetonitril at a flow rate of 0.8 ml/min. A UV/Vis detector set at 225 nm was used for detection. The stability testing was carried out under acidic (pH 1.2 and pH 4.5), normal (pH 6.8) and alkaline (pH 13) conditions at temperature of 37°C. At moderate and low alkali pH and temperatures the compound was stable. In acidic media the model compound is transformed into its degradation product. The developed method is validated with respect to suitability, linearity, precision, accuracy and selectivity and can be implemented for stability testing of pyrrolecontaining ester derivatives. Correspondence to: Maya Boyanova Georgieva, PhD, Department of Pharmaceutical chemistry, Faculty of Pharmacy, Medical University-Sofia, 1000, Sofia, Bulgaria, Tel: +35929236530; Fax:+35929236505; E-mail: georgm@mail.bg
Nine pyrrole-containing compounds were designed introducing reasonable structural novelties withi... more Nine pyrrole-containing compounds were designed introducing reasonable structural novelties within the framework of the architecture of confirmed tuberculostatics. The new products were synthesized via adopted Paal-Knorr cyclization by condensation of three 1,4-dicarbonyl compounds with a set of substituted anilines, acting as primary amines. Preliminary in vitro tests have already registered encouraging anti-Mycobacterium tuberculosis activity.
Acta Pharmaceutica, 2020
Six new N-pyrrolylhydrazide hydrazones were synthesized under micro synthesis conditions, assurin... more 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....
Folia Medica, Jun 1, 2018
Acta Pharmaceutica, Feb 17, 2020
, in vitro safety and antioxidant activity of new pyrrole hydrazones Six new N-pyrrolylhydrazide ... more , in vitro safety and antioxidant activity of new pyrrole hydrazones 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, 1 H and 13 C 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-pyrrole-3-carboxylate (4d) and ethyl 5-(4-bromophenyl)-1-(1-(2-(2hydroxybenzylidene)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.
Heterocyclic Communications, Mar 31, 2014
Twenty new N-pyrrolylcarboxylic acids were designed to assume the architecture of contemporary se... more Twenty new N-pyrrolylcarboxylic acids were designed to assume the architecture of contemporary selective COX-2 inhibitors as potential anti-inflammatory agents. The targeted products were synthesized in 70-82% yields by Paal-Knorr cyclization of a set of eight amino acids, acting as primary amines, and four 1,4-dicarbonyl compounds. The latter substrates were prepared by C-alkylation of three commercially available β-dicarbonyl compounds with two ω-bromoacetophenones and used in situ. These compounds inhibit carrageenin-induced rat paw edema and show analgesic activity.
Tropical Journal of Pharmaceutical Research, Feb 18, 2023
Purpose: To screen a series of newly synthesized N-pyrrolyl hydrazide hydrazones for analgesic ac... more 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.
European Neuropsychopharmacology, 2019
Protein and Peptide Letters, Sep 1, 2007
Фармация, Apr 5, 2022
Development and validation of an RP-HPLC method for analysis of 2-(5-(4-chlorophenyl)-3-(ethoxyca... more 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.
Pharmaceutical Chemistry Journal, 2022
Two new N-pyrrolylcarboxylic acids were synthesized via Paal-Knorr cyclization by condensation of... more Two new N-pyrrolylcarboxylic acids were synthesized via Paal-Knorr cyclization by condensation of γ-aminobutyric acid and 1,4-dicarbonyl compounds. The obtained structures were elucidated by IR and 1 H-NMR spectral data and their purity was proven by TLC characteristics and melting points. The corresponding phytochemical activity of the obtained compounds on wheat and cucumber cultivars in three concentrations was studied. Both molecules were tested at 4 concentrations for herbicidal activity whereat no concentration dependence of the herbicidal effects was established. The inhibition of growth of the aerial parts and roots at the lowest (0.001 mM) and the highest (1 mM) concentration of the compounds was comparable. In addition a number of structural parameters were calculated for the target compounds and some analogues thereof. A second degree polynomial structure-activity dependency on the herbicidal effects from the corresponding miLogP was observed with R 2 in the range of 0.79...
Pyrrole is widely known as a biologically active scaffold which possesses a diverse nature of act... more 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.
Pharmacology, Drug Development & Therapeutics, 2016
This paper proposes a simple and selective UHPLC method for determination of degradation products... more This paper proposes a simple and selective UHPLC method for determination of degradation products of a model pyrrole based compound, containing susceptible to hydrolysis ester group. The chromatographic separation was achieved on BDSHYPERSILC18 (150 mm × 4.6 mm, 3.5 μm) column thermostated at 30°C under gradient elution by a binary mixture of potassium dihydrogen phosphate (pH 3.0, 0.02 M) and acetonitril at a flow rate of 0.8 ml/min. A UV/Vis detector set at 225 nm was used for detection. The stability testing was carried out under acidic (pH 1.2 and pH 4.5), normal (pH 6.8) and alkaline (pH 13) conditions at temperature of 37°C. At moderate and low alkali pH and temperatures the compound was stable. In acidic media the model compound is transformed into its degradation product. The developed method is validated with respect to suitability, linearity, precision, accuracy and selectivity and can be implemented for stability testing of pyrrolecontaining ester derivatives. Correspondence to: Maya Boyanova Georgieva, PhD, Department of Pharmaceutical chemistry, Faculty of Pharmacy, Medical University-Sofia, 1000, Sofia, Bulgaria, Tel: +35929236530; Fax:+35929236505; E-mail: georgm@mail.bg
Nine pyrrole-containing compounds were designed introducing reasonable structural novelties withi... more Nine pyrrole-containing compounds were designed introducing reasonable structural novelties within the framework of the architecture of confirmed tuberculostatics. The new products were synthesized via adopted Paal-Knorr cyclization by condensation of three 1,4-dicarbonyl compounds with a set of substituted anilines, acting as primary amines. Preliminary in vitro tests have already registered encouraging anti-Mycobacterium tuberculosis activity.
Acta Pharmaceutica, 2020
Six new N-pyrrolylhydrazide hydrazones were synthesized under micro synthesis conditions, assurin... more 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....