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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease VI.
Ludvik, Matěj ; Chlebek, Jakub (advisor) ; Šafratová, Marcela (referee)
Ludvik M., Papaver rhoeas L. (Papaveraceae) alkaloids and their activity related to Alzheimer disease VI., diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové 2023, number of pages 69. This diploma thesis was focused on alkaloids from combined fractions 13-15 of diethylether extract from Papaver rhoeas L. The methods used for extraction of the alcaloids include flash chromatography and preparative thin-layer chromatography. The structures of isolated compounds were determined by using mass spectrometric and spectrophotometric methods (GC-MS, NMR and optical rotation). Alkaloids were identified as galanthamine and N,N-dimethyltryptamine. Subsequently, N,N-dimethyltryptamine was tested for its biological activity against human cholinesterases, specifically acetylcholinesterase and butyrylcholinesterase. Galanthamine was not tested on ability to inhibit cholinesterase, since the compound has been already tested on this activity at the Department of Pharmacognosy and Pharmaceutical Botany. N,N-dimethyltryptamine showed mild inhibitory activity against butyrylcholinesterase (IC50 = 44,14 ± 1,76) and no activity against acetylcholinesterase (IC50 = >100). Despite its mild activity towards butyrylcholinesterase, N,N-dimethyltryptamine can't be used in therapy of Alzheimer's disease,...
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease V.
Dušánková, Zita ; Chlebek, Jakub (advisor) ; Hošťálková, Anna (referee)
Dušánková Z.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs diesease V.; Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacognozy and Pharmaceutical Botany, Hradec Králové 2023, pages 72. The aim of this diploma thesis was focused on isolation of alkaloids from a combined fraction 7-8 of an alkaloidal diethyl ether (Et2O) extract of aerial parts of Papaver rhoeas L. (Papaveraceae). Column chromatography (flash chromatography), planar chromatography (preparative TLC) and crystallization were used for the isolation of alkaloids. The structures of isolated substances were elucidated using NMR, GC-MS methods and optical rotation. Isolated alkaloids were identified as ZD-1, (+)-3,4-dehydrotheaspirone, (±)-juziphine, (+)-lirinidine and protopine. Alkaloids were tested for biological activity against enzymes (acetylcholinesterase, butyrylcolinesterase and prolyl oligopeptidase). (+)-3,4-Dehydrotheaspirone, (±)-juziphine, and protopine did not show significant inhibitory activities against cholinesterases (IC50 values >100 µM). Protopine was also inactive against prolyl oligopeptidase (IC50 >1000 µM ). (+)-Lirinidine showed a moderate inhibitory activity against BuChE (IC50 value of 23,45 ± 0,55 µM), towards...
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease IV.
Gergely, Eszter ; Chlebek, Jakub (advisor) ; Hradiská Breiterová, Kateřina (referee)
Gergely, E.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease IV. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacognosy and Pharmaceutical Botany, Hradec Králové 2022, 61 pages. A chloroform alkaloid extract of aerial parts of Papaver rhoeas L. (Papaveraceae) showed a significant inhibitory activity on human butyrylcholinesterase (IC50hBuChE = 3,94 ± 0,35 µg/ml) [1,2]. hBuChE represents a key enzyme playing an important role in the pathogenesis of Alzheimer's disease. The main aim of this study was to isolate pure alkaloids by bio-guided assay using flash chromatography and preparative TLC, elucidate their structures (MS, NMR, and optical rotation) and cholinesterase inhibitory activity with Ellman's spectrophotometric method. Prediction of possibility of the molecules' crossing through blood-brain barrier (BBB) via logBB was calculated. Potential non-cytotoxicity of the most active compound was screened on selected nine cancer cell lines and one non-cancer cell line MRC-5. The identified isolated alkaloid (+)-caaverine showed a promising and selective hBuChE inibition (IC50hBuChE = 4,09 ± 0,50 µM and IC50hAChE > 100 µM, respectively) and should be able to cross the BBB (logBB = 0,372) by...
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Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease III.
Bučková, Anna ; Chlebek, Jakub (advisor) ; Suchánková, Daniela (referee)
Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease III. ABSTRACT Bučková, A.: Alkaloids of Papaver rhoeas L. (Papaveraceae) and their biological activity related to Alzheimerʼs disease III.; Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacognosy and Pharmaceutical Botany, Hradec Králové 2022, 59 pages The aim of this diploma thesis was to fractionate the combined extract (CHCl3 +EtOAc + I- ) from Papaver rhoeas L. using flash chromatography and subsequently, to isolate alkaloids from the chosen factions by preparative TLC. The chemical structures of the isolated compounds were determined by spetrometric and spectroscopic methods (MS, NMR and optical rotation). Alkaloids were identified as (+)-rhoeadin, (+)-rhoeagenin a (+)-isorhoeagenin. After structure elucidation, the alkaloids were tested in vitro for inhibitory activity towards enzymes that are playing part in the pathogenesis of the Alzheimer's disease (acetylcholinesterase, butyrylcholinesterase a prolyloligopeptidase). Based on the results, the studied alkaloids seem to be inactive towards chosen enzymes (values IC50 > 100 µM). Key words: Papaver rhoeas, Papaveraceae, Alzheimerʼs disease, acetylcholinesterase, butyrylcholinesterase, prolyl...
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Study of biological activity of alkaloids isolated from Fumaria officinalis L. (Fumariaceae) I.
Kostelník, Jan ; Chlebek, Jakub (advisor) ; Cahlíková, Lucie (referee)
Kostelník, J.: Study of biological activity of alkaloids isolated from Fumaria officinalis L. (Fumariaceae) I. Diploma thesis, Charles University in Prague,Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2014, 63 p. The aim of this study was to isolate alkaloids from joined fraction no. 55-67 (A2) obtained from the total alkaloid fraction of extract of Fumaria officinalis L. (Fumariaceae) plant. Using chromatography methods three alkaloids were isolated and then identified by structural analysis (GC-MS, NMR). Three alkaloids were isolated by using common chromagografic methods and then identified by structural analyses optical rotation and melting point as (-)-O- methylfumarophycine, (-)-sinactine a (-)-stylopine. Inhibitory activity of isolated alkaloids was assessed against human erythrocyte acetylcholinesterase, human butyrylcholineesterase and prolyl oligopeptidase. The results were expressed as IC50 values ((-)-stylopine: IC50 AChE and IC50 BuChE > 1000 μM, IC50 POP > 1000 mM; (-)-O-methylfumarophycine: IC50 AChE = 963.10 ± 135.98 µM, IC50 BuChE = 1771.0 ± 380.94 µM, IC50 POP - unmeasured; (-)-sinactine IC50 AChE = 632.0 ± 68.12 µM, IC50 BuChE = 8154.3 ± 981.42 µM, IC50 POP = IC50 POP = 52.9 ± 1.8 µM). None of alkaloids isolated showed...
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Study of biological activity of alkaloids isolated from Fumaria officinalis L. (Fumariaceae) II.
Malý, Lukáš ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Malý, L.: Study of biological activity of alkaloids isolated from Fumaria officinalis L. (Fumariaceae) II. Diploma Thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2014, 49 pp. Obtained diethylether extract of Fumaria officinalis L. was separated to fractions in column chromatography with petrol, chloroform and ethanol. Preparative TLC and crystalisation led to isolation of five alkaloids from fraction. Alkaloids were identified by GC-MS and NMR specters, optical rotation and melting point as protopine, cryptopine, (-)-fumaricine, (+)-fumariline and (+)-parfumidine. Isolated alkaloids were tested for their inhibition activity towards acetyl- and butyrylcholinesterase and towards prolyloligopeptidase. Activities were compared with standards. Natural inhibitor galanthamine showed IC50 AChE 1.710 ± 0.065 µM, IC50 BuChE 42.30 ± 1.30 µM. Best inhibition activity showed protopine (IC50 AChE 345.4 ± 24 µM, IC50 BuChE 239.6 ± 22.3 µM) and cryptopine (IC50 AChE 477.71 ± 47.33 µM, IC50 BuChE 270.82 ± 39.12 µM). The highest prolyloligopeptidase inhibition activity showed (+)-parfumidine with IC50 POP 99.2 µM, which was more active than used natural inhibitor baicaline (IC50 POP 605.9 ± 0.021 µM). Synthetic POP...
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Study of biological activity of alkaloids isolated from Fumaria officinalis L. (Fumariaceae) II.
Malý, Lukáš ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Malý, L.: Study of biological activity of alkaloids isolated from Fumaria officinalis L. (Fumariaceae) II. Diploma Thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2014, 49 pp. Obtained diethylether extract of Fumaria officinalis L. was separated to fractions in column chromatography with petrol, chloroform and ethanol. Preparative TLC and crystalisation led to isolation of five alkaloids from fraction. Alkaloids were identified by GC-MS and NMR specters, optical rotation and melting point as protopine, cryptopine, (-)-fumaricine, (+)-fumariline and (+)-parfumidine. Isolated alkaloids were tested for their inhibition activity towards acetyl- and butyrylcholinesterase and towards prolyloligopeptidase. Activities were compared with standards. Natural inhibitor galanthamine showed IC50 AChE 1.710 ± 0.065 µM, IC50 BuChE 42.30 ± 1.30 µM. Best inhibition activity showed protopine (IC50 AChE 345.4 ± 24 µM, IC50 BuChE 239.6 ± 22.3 µM) and cryptopine (IC50 AChE 477.71 ± 47.33 µM, IC50 BuChE 270.82 ± 39.12 µM). The highest prolyloligopeptidase inhibition activity showed (+)-parfumidine with IC50 POP 99.2 µM, which was more active than used natural inhibitor baicaline (IC50 POP 605.9 ± 0.021 µM). Synthetic POP...
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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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Study of biological activity of alkaloids isolated from Fumaria officinalis L. (Fumariaceae) II.
Malý, Lukáš ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Malý, L.: Study of biological activity of alkaloids isolated from Fumaria officinalis L. (Fumariaceae) II. Diploma Thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2014, 49 pp. Obtained diethylether extract of Fumaria officinalis L. was separated to fractions in column chromatography with petrol, chloroform and ethanol. Preparative TLC and crystalisation led to isolation of five alkaloids from fraction. Alkaloids were identified by GC-MS and NMR specters, optical rotation and melting point as protopine, cryptopine, (-)-fumaricine, (+)-fumariline and (+)-parfumidine. Isolated alkaloids were tested for their inhibition activity towards acetyl- and butyrylcholinesterase and towards prolyloligopeptidase. Activities were compared with standards. Natural inhibitor galanthamine showed IC50 AChE 1.710 ± 0.065 µM, IC50 BuChE 42.30 ± 1.30 µM. Best inhibition activity showed protopine (IC50 AChE 345.4 ± 24 µM, IC50 BuChE 239.6 ± 22.3 µM) and cryptopine (IC50 AChE 477.71 ± 47.33 µM, IC50 BuChE 270.82 ± 39.12 µM). The highest prolyloligopeptidase inhibition activity showed (+)-parfumidine with IC50 POP 99.2 µM, which was more active than used natural inhibitor baicaline (IC50 POP 605.9 ± 0.021 µM). Synthetic POP...
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Study of biological activity of alkaloids isolated from Fumaria officinalis L. (Fumariaceae) I.
Kostelník, Jan ; Chlebek, Jakub (advisor) ; Cahlíková, Lucie (referee)
Kostelník, J.: Study of biological activity of alkaloids isolated from Fumaria officinalis L. (Fumariaceae) I. Diploma thesis, Charles University in Prague,Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2014, 63 p. The aim of this study was to isolate alkaloids from joined fraction no. 55-67 (A2) obtained from the total alkaloid fraction of extract of Fumaria officinalis L. (Fumariaceae) plant. Using chromatography methods three alkaloids were isolated and then identified by structural analysis (GC-MS, NMR). Three alkaloids were isolated by using common chromagografic methods and then identified by structural analyses optical rotation and melting point as (-)-O- methylfumarophycine, (-)-sinactine a (-)-stylopine. Inhibitory activity of isolated alkaloids was assessed against human erythrocyte acetylcholinesterase, human butyrylcholineesterase and prolyl oligopeptidase. The results were expressed as IC50 values ((-)-stylopine: IC50 AChE and IC50 BuChE > 1000 μM, IC50 POP > 1000 mM; (-)-O-methylfumarophycine: IC50 AChE = 963.10 ± 135.98 µM, IC50 BuChE = 1771.0 ± 380.94 µM, IC50 POP - unmeasured; (-)-sinactine IC50 AChE = 632.0 ± 68.12 µM, IC50 BuChE = 8154.3 ± 981.42 µM, IC50 POP = IC50 POP = 52.9 ± 1.8 µM). None of alkaloids isolated showed...
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