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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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Vinca minor L. alkaloids and their biological activity (inhibition of human cholinesterases) V.
Vašíčková, Alžběta ; Chlebek, Jakub (advisor) ; Hošťálková, Anna (referee)
Vašíčková A.: Alkaloids of Vinca minor L. and their biological activity (inhibition of human cholinesterases) V. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové 2020. From the selected fraction VM 215-258 were isolated 3 alkaloids by flash chromatography followed, preparative thin layer chromatography and crystallization. Their structure was determined by mass spectroscopy, NMR and optical rotation, and the obtained data were compared with those in literature. Strictamine and minovincinine belong to alkaloids previously isolated, the alkaloid AV-3 has not been isolated yet. These alkaloids were tested for their ability to inhibit human cholinesterases and their inhibitory activity was compared to standards galanthamine and physostigmine. Compound AV-3 showed mild inhibitory activity against BChE (IC50 μM > 86.3 ± 2.3), other alkaloids were considered inactive, their IC50 values against cholinesterases were > 100 μM. Key words: Vinca minor L. (Apocynaceae), vinca alkaloids, minovincinine, strictamine, Alzheimer's disease, acetylcholinesterase, butyrylcholinesterase.
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Vinca minor L. alkaloids and their biological activity III.
Valová, Dominika ; Chlebek, Jakub (advisor) ; Hradiská Breiterová, Kateřina (referee)
Valová D.: Vinca minor L. alkaloids and their biological activity III. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové, 2020, 75 p. Alzheimer's disease (AD) is a progressive, neurodegenerative disorder and it's the most common form of dementia. Because we're still not able to treat the cause of disease, searching for a new substance is relevant. This thesis is focused on isolation of alkaloids from a Vinca minor L. alkaloidal extract as a potential drug. The preparation and column chromatography of the summary extract were performed by Ing. Miroslav Ločárek as a part of his doctoral studies. Subsequent preparative TLC led to the isolation of three compounds. The chemical structures of the isolated alkaloids were elucidated by means of optical rotation, NMR and MS analyses and by comparison of the obtained data with those in the literature. One of the compounds was determined as(-)-vincine, other two compounds have not been isolated yet. Isolated compounds were also tested for their biological activity. Vincine, DV-1 a DV-3 were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Additionally, vincine and DV-3 were also tested for their inhibitory activity on prolyl...
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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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Use of kinase modulation in the Alzheimerʼs disease pathogenesis.
Polzerová, Iveta ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Polzerová, I: Use of kinase modulation in the Alzheimer's disease pathogenesis. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2016, 91 p. Data used in this Diploma Thesis have been taken from foreigner scientific literary sources. It provides the summary of the not yet explored natural compounds from marine organisms with kinase inhibitory activity. The first chapter Alzheimer's disease describes a characteristic of the disease, its etiopathogenesis, risk factors and currently available treatment. At the beginning of the second chapter are mentioned new perspective approaches to treatment of Alzheimer's disease. Most of this chapter deals with kinases as potential therapeutic targets in the treatment of Alzheimer's disease. In the chapter, physiologic and pathophysiologic functions of GSK-3β and CK-1δ are described in the organism, and also, other kinases are mentioned which are involved in the pathogenesis of the disease. Next part dedicates analytical methods suitable for testing activity and inhibition of kinases in vitro and in silico, also deals with summary of the synthetic kinase inhibitors and characterizes an their properties. In this chapter is also described main part of this work - the...
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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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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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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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