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Cytotoxic and cholinesterase inhibitory activity of extracts from selected species of the Centaurea L. genus
Faschingbauer, Jakub ; Chlebek, Jakub (advisor) ; Šafratová, Marcela (referee)
Faschingbauer J.: Cytotoxic and cholinesterase inhibitory activity of extracts from selected species of the Centaurea L. genus. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové, 2019. During the screening of biologically active secondary metabolites of plants carried out at the Department of Pharmaceutical Botany FAF UK, selected taxa of the genus Centaurea (Asteraceae) were investigated. This study is focused on a basic phytohemical research of extracts prepared from Centaurea cyanus, Centaurea jacea, Centaurea scabiosa, Centaurea pseudophrygia, Centuarea stoebe, Centaurea solstitialis a Centaurea benedicta. Extracts were prepared for evidence of the proof reactions of TLC and MS analysis (EI, ESI) to clarify a potential presence of alkaloids. EtOAc and ethanol extracts were evaluated for potential inhibitory activity against human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) and cytotoxicity against selected 9 tumor lines. C. cyanus alkaloid extract had interesting cholinesterase activity which selectively inhibited BChE (IC50 BChE = 22.62 ± 3.62 μg / ml, IC50 AChE = 221.50 ± 44.56 g / ml). Other EtOAc extracts of selected Centaurea species were considered inactive (IC50 > 100 μg/ml)....
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Pharmacological evaluation of potencial drugs for Alzheimer's disease treatment
Matoušková, Lenka ; Vopršalová, Marie (advisor) ; Říha, Michal (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lenka Matoušková Supervisor: PharmDr. Marie Vopršalová, CSc. Consultant: PharmDr. Vendula Šepsová, Ph.D. Title of diploma thesis: Pharmacological evaluation of potencial drugs for Alzheimer's disease treatment Alzheimer's disease (AD) is a neurodegenerative disease characterized by aggregates of beta-amyloid, neurofibrillary tangles of tau protein and by the loss of cholinergic neurons in the basal forebrain and hippocampus. Cause of AD is still unknown and only symptomatic treatment is available thanks to inhibitors of acetylcholinesterase (AChE) and memantine, inhibitor of glutamate receptors. M1 muscarinic positive allosteric modulators (PAM) represent another variant of treatment that can improve cholinergic transmission. Thanks to their selectivity, they are able to decrease side effects. The aim of the study was to measure novel compounds' abilities to inhibit AChE and BChE and simultaneously act as PAM of M1 receptors. Enzymes inhibition was measured according to Ellman's method and IC50 values were determined. For fluorescent measurement of compounds interaction with muscarinic receptor the CHO cell line stably expressing the M1 receptor subtype was used. Statistical analysis...
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease II.
Čakurdová, Marta ; Chlebek, Jakub (advisor) ; Hošťálková, Anna (referee)
Čakurdová, M.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimer's disease II. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové, 2017. The aim of this work was focused on isolation of alkaloids from the fraction 1 (joined fractions 20-27), which was obtained from the summary alkaloid extract of Papaver rhoeas L. (Papaveraceae). The alkaloids were identified by structural analysis NMR, GC-MS, optical activity and melting point. Two alkaloids were identified as (-)-stylopine and (+)-rhoeadine. Isolated substances were tested on ability to inhibit the enzymes acetylcholinesterase, butyrylcholinesterase and prolyloligopeptidase. Obtained data were expressed as IC50 values: (-)-stylopine (IC50 AChE = 522 ± 67 µM, IC50 BuChE = >1000 µM, IC50 POP = >790 µM); (+)-rhoeadine (IC50 AChE = 915 ± 64 µM, IC50 BuChE = >1000 µM, IC50 POP = >790 µM). None of the isolated substances showed so potent cholinesterase inhibitory activity as the alkaloids galanthamine (IC50 AChE = 1.71± 0.065 µM, IC50 BuChE =42.30 ± 1.30 µM) and huperzine A (IC50 AChE = 0.033 ± 0.001 µM, IC50 BuChE = >1000 µM) or rivastigmine (IC50 AChE = 0.037 ± 0.001 µM, IC50 BuChE = 3.3 ± 0.3 nM)....
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Study of biological activity of isolated alkaloids from Argemone grandiflora (Papaveraceae)II.
Michal, Vojtěch ; Chlebek, Jakub (advisor) ; Ločárek, Miroslav (referee)
Michal, Vojtěch: STUDY OF BIOLOGICAL ACTIVITY OF ISOLATED ALKALOIDS FROM ARGEMONE GRANDIFLORA (PAPAVERACEAE) II. Diploma thesis 2015. Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology. Supervisor: PharmDr. Jakub Chlebek, PhD. Key words: Argemone grandiflora Sweet, Papaveraceae, alkaloids, isolation, acetylcholinesterase, butyrylcholinesterase, prolyloligopeptidase, Alzheimerʼs disease, in vitro assay. Diethylether alkaloid extract obtained from stem and roots of Argemone grandiflora Sweet was chromatografically analyzed. Using common chromatografic methods, three alkaloids were isolated in clean form. These substances were identified as allocryptopine, (-)-munitagine and (-)-norargemonine by structural analysis (MS, NMR). These obtained alkaloids were tested for their inhibitory activity against human erythrocyte acetylcholinesterase (AChE) and human plasma butyrylcholinestrase (BuChE) by Ellman's method. The results were represented as IC50 values (allocryptopine: IC50 AChE = 250,0 ± 2,52 μM, IC50 BuChE = 530 ± 28,2 μM; (-)-munitagine: IC50 AChE = 62,29 ± 5,81 μM, IC50 BuChE = 837,4 ± 23,03 μM; (-)-norargemonine: IC50 AChE = 205,17 ± 11,6 μM, IC50 BuChE = 4158,20 ± 495,78 μM). Inhibition against prolyloligopeptidase was tested for...
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Biological aktivity of secondary plants metabolites II. Alkaloids of Narcissus jonquilla L.
Jílek, Lukáš ; Ločárek, Miroslav (advisor) ; Cahlíková, Lucie (referee)
Jílek L.: The biological activity of secondary plants metabolites II. Alkaloids of Narcissus jonquilla L. Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2015, pp. 74. The aim of the diploma thesis was a preparation of alkaloid extracts to identification of alkaloid patterns and measure cholinesterase inhibitory activity. This activity is useful for treating Alzheimer's disease. Alkaloid extracts of seven Narcissus jonquilla L. (Amaryllidaceae) varieties (Bella Estrella, Bell Song, Fruit Cup, Hill Star, Chit Chat, Martinette, Dick Sickel) were studied with respect to their acetylcholinesterase (HuAChE) and butyrylcholinesterase (HuBuChE) inhibitory activity and alkaloid patterns. Thirteen different alkaloids were identified from their mass spectra and retention times. All samples exhibited content of tazettine, most samples contained lycoramine and galanthamine. Promising HuAChE inhibition activity was demonstrated by Narcissus jonquilla L. cv. Bell Song with IC50 values of 6,19 ± 0,85 μg/mL. The strongest inhibitory activity against HuBuChE was detected in extract from Narcissus jonquilla L. cv. Bella Estrella with IC50 value of 18,39 ± 1,51 μg/mL. Keywords: Alzheimer's disease, Amaryllidaceae, Narcissus, GC/MS,...
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease I.
Bulvová, Leontina ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Bulvová, L.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease I. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2017. The aim of this study was to process the summary alkaloidal extract of aerial parts of Papaver rhoeas L.; to isolate contained alkaloids using chromatographical methods; to identify them and to determine their inhibitory activity towards human enzymes acetylcholinesterase, butyrylcholinesterase and prolyloligopeptidase. Two alkaloids (+)-rhoeagenine and LB-2 were isolated, and the structure of LB-2 (its absolute configuration) is being determined nowadays. In vitro biological assays of these alkaloids found the following results: (+)-rhoeagenine (IC50 AChE ˃ 1000 μM, IC50 BuChE = 230 ± 10 μM, IC50 POP = 878 ± 45 μM) and LB-2 (IC50 AChE ˃ 1000 μM, IC50 BuChE = 314 ± 13 μM, IC50 POP = 706 ± 2 μM). The determined IC50 values of isolated alkaloids were compared with inhibitory standards of cholinesterases galanthamine (IC50 AChE = 1,71 ± 0,065 μM, IC50 BuChE = 42,30 ± 1,30 μM), huperzine A (IC50 AChE = 0,033 ± 0,001 μM, IC50 BuChE > 1000 μM, IC50 POP > 1000 μM) and rivastigmine (IC50 AChE = 0,037 ± 0,001 μM, IC50 BuChE = 0,0033 ± 0,0003...
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Alkaloids of Narcissus 'Dutch Master' (Amaryllidaceae) and their biological activity III.
Rýdlová, Kateřina ; Chlebek, Jakub (advisor) ; Cahlíková, Lucie (referee)
Rýdlová Kateřina: Alkaloids Narcissus 'Dutch Master' (Amaryllidaceae) and their biological activity III. Diploma thesis 2017. Charles university in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology. The aim of this work was isolation of compounds from the selected fraction ND 3 - 5 obtained by column chromatography of a Narcissus 'Dutch Master' alkaloid extract. Preparation of the extract and its column chromatography was performed by Mgr. Daniela Hulcová as a part of her doctoral study. Two substances NDM-1 and NDM-2 were isolated from fraction ND 3 - 5 by column chromatography and preparative TLC. The structures were determined as (+)-masonine and (+)-homolycorine on the basis of NMR, GC-MS analysis, optical rotation and their comparison with literature data. Isolated alkaloids were tested on inhibitory activity against human erythrocyte acetylcholinesterase, plasma butyrylcholinesterase and prolyloligopeptidase. Activity of alkaloids was expressed as IC50 values: (+)-masonine (IC50 AChE = 305 ± 34 μM, IC50 BuChE = 229 ± 24 μM, IC50 POP = 314 ± 34 μM), (+)-homolycorine (IC50 AChE = 63.7 ± 4.3 μM, IC50 BuChE = 151 ± 20 μM, IC50 POP = 173 ± 41 μM). In comparison with standards of galanthamine (IC50 AChE = 1.710 ± 0.1 μM, IC50 BuChE = 42.3 ± 1.3 μM),...
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease II.
Čakurdová, Marta ; Chlebek, Jakub (advisor) ; Hošťálková, Anna (referee)
Čakurdová, M.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimer's disease II. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové, 2017. The aim of this work was focused on isolation of alkaloids from the fraction 1 (joined fractions 20-27), which was obtained from the summary alkaloid extract of Papaver rhoeas L. (Papaveraceae). The alkaloids were identified by structural analysis NMR, GC-MS, optical activity and melting point. Two alkaloids were identified as (-)-stylopine and (+)-rhoeadine. Isolated substances were tested on ability to inhibit the enzymes acetylcholinesterase, butyrylcholinesterase and prolyloligopeptidase. Obtained data were expressed as IC50 values: (-)-stylopine (IC50 AChE = 522 ± 67 µM, IC50 BuChE = >1000 µM, IC50 POP = >790 µM); (+)-rhoeadine (IC50 AChE = 915 ± 64 µM, IC50 BuChE = >1000 µM, IC50 POP = >790 µM). None of the isolated substances showed so potent cholinesterase inhibitory activity as the alkaloids galanthamine (IC50 AChE = 1.71± 0.065 µM, IC50 BuChE =42.30 ± 1.30 µM) and huperzine A (IC50 AChE = 0.033 ± 0.001 µM, IC50 BuChE = >1000 µM) or rivastigmine (IC50 AChE = 0.037 ± 0.001 µM, IC50 BuChE = 3.3 ± 0.3 nM)....
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease I.
Bulvová, Leontina ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Bulvová, L.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease I. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2017. The aim of this study was to process the summary alkaloidal extract of aerial parts of Papaver rhoeas L.; to isolate contained alkaloids using chromatographical methods; to identify them and to determine their inhibitory activity towards human enzymes acetylcholinesterase, butyrylcholinesterase and prolyloligopeptidase. Two alkaloids (+)-rhoeagenine and LB-2 were isolated, and the structure of LB-2 (its absolute configuration) is being determined nowadays. In vitro biological assays of these alkaloids found the following results: (+)-rhoeagenine (IC50 AChE ˃ 1000 μM, IC50 BuChE = 230 ± 10 μM, IC50 POP = 878 ± 45 μM) and LB-2 (IC50 AChE ˃ 1000 μM, IC50 BuChE = 314 ± 13 μM, IC50 POP = 706 ± 2 μM). The determined IC50 values of isolated alkaloids were compared with inhibitory standards of cholinesterases galanthamine (IC50 AChE = 1,71 ± 0,065 μM, IC50 BuChE = 42,30 ± 1,30 μM), huperzine A (IC50 AChE = 0,033 ± 0,001 μM, IC50 BuChE > 1000 μM, IC50 POP > 1000 μM) and rivastigmine (IC50 AChE = 0,037 ± 0,001 μM, IC50 BuChE = 0,0033 ± 0,0003...
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Alkaloids of Narcissus 'Dutch Master' (Amaryllidaceae) and their biological activity III.
Rýdlová, Kateřina ; Chlebek, Jakub (advisor) ; Cahlíková, Lucie (referee)
Rýdlová Kateřina: Alkaloids Narcissus 'Dutch Master' (Amaryllidaceae) and their biological activity III. Diploma thesis 2017. Charles university in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology. The aim of this work was isolation of compounds from the selected fraction ND 3 - 5 obtained by column chromatography of a Narcissus 'Dutch Master' alkaloid extract. Preparation of the extract and its column chromatography was performed by Mgr. Daniela Hulcová as a part of her doctoral study. Two substances NDM-1 and NDM-2 were isolated from fraction ND 3 - 5 by column chromatography and preparative TLC. The structures were determined as (+)-masonine and (+)-homolycorine on the basis of NMR, GC-MS analysis, optical rotation and their comparison with literature data. Isolated alkaloids were tested on inhibitory activity against human erythrocyte acetylcholinesterase, plasma butyrylcholinesterase and prolyloligopeptidase. Activity of alkaloids was expressed as IC50 values: (+)-masonine (IC50 AChE = 305 ± 34 μM, IC50 BuChE = 229 ± 24 μM, IC50 POP = 314 ± 34 μM), (+)-homolycorine (IC50 AChE = 63.7 ± 4.3 μM, IC50 BuChE = 151 ± 20 μM, IC50 POP = 173 ± 41 μM). In comparison with standards of galanthamine (IC50 AChE = 1.710 ± 0.1 μM, IC50 BuChE = 42.3 ± 1.3 μM),...
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