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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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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 from Narcissus pseudonarcissus L. cv. Dutch Master and their cholinesterase and prolyl oligopeptidase inhibitory activity.
Farkašovský, Marek ; Chlebek, Jakub (advisor) ; Siatka, Tomáš (referee)
Farkašovský Marek: Alkaloids from Narcissus pseudonarcissus L. cv. Dutch Master and their cholinesterase and prolyl oligopeptidase inhibition activity. Rigorous thesis 2017, Charles university, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology. The content of this work was isolation of minimum two compound from alkaloid fraction ND 3 - 5/2, obtained by column chromatography of Narcissus pseudonarcissus L. cv. Dutch Master alkaloid extract. Preparation of extract and its column chromatography was performed by Mgr. Daniela Hulcová as a part of her doctoral studies. Two different alkaloids were isolated with preparative TLC method. Their structure was determined with optical rotation, MS (EI, ESI), 1H NMR and 13C NMR analysis. Obtained data were compared with facts with those in literature. The first isolated compound was lycorine type alkaloid O-acetylpluvine. Its inhibition activity compared to positive standards (galanthamine, huperzine A, physostigmine, berberine and Z-pro-prolinal) was mild - IC50 AChE: 684 ± 54 µM, IC50 BuChE: 603 ± 49 µM, IC50 POP ˃1000 µM. From the point of its cholinesterase and POP inhibition, this results make O-acetylpluvine unusable compound in treatment of AD. The second isolated compound was a new alkaloid, which has not been...
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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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Alkaloids of Narcissus 'Dutch Master '(Amaryllidaceae) and their biological activity. I.
Vacková, Lucie ; Chlebek, Jakub (advisor) ; Hošťálková, Anna (referee)
Vacková, L.: Alkaloids Narcissus 'Dutch Master' (Amaryllidaceae) and their biological activity. I. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2016. From a selected fraction ND-6, which was obtained by column chromatography of an alkaloid extract of Narcissus 'Dutch Master' (preparation of the alkaloid extract and column chromatography was performed by Mgr. Daniela Hulcová within her doctoral thesis), lycorine alakloid O-acetylpluviin was isolated using preparative TLC. Its structure was determined on the basis of MS, NMR analysis, and optical rotation, the obtained data were compared with the literature. The isolated alkaloid was tested on its possibility to inhibit human acetylcholinesterase and butyrylcholinesterase. The activity was expressed as IC 50 values (IC50 AChE = 648.03 ± 53.95 μM, IC50 BChE = 602.50 ± 48.50 μM) and compared with IC50 values of galanthamine, huperzine A and physostigmine. O-acetylpluviine showed a very low inhibitory cholinesterase activity, and so, the alkaloid does not seem to be a suitable cholinesterase inhibitor for potential use in the treatment of Alzheimer's disease. Keywords: Narcissus 'Dutch Master', Amaryllidaceae, lycorine alkaloids, Alzheimer's disease,...
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Alkaloids of Narcissus'Dutch Master ' (Amaryllidaceae) and their biological activity. II.
Dvořáková, Zdeňka ; Chlebek, Jakub (advisor) ; Ločárek, Miroslav (referee)
Dvořáková Zdeňka: Alkaloids of Narcissus 'Dutch Master' (Amaryllidaceae) and their biological activity II. Diploma thesis 2016, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology. The content of this work was isolation of compounds from the selected fraction ND-6 obtained by column chromatography of Narcissus 'Dutch Master' alkaloid extract. Preparation of extract and its column chromatography was performed by Mrg. Daniela Hulcová as part of her doctoral studies. By the means preparative TLC was from fraction ND- 6 homolycorine type alkaloid (+)-O-methyllycorenine gained. Its structure was determined on the basis NMR, GC-MS analysis and optical rotation. The obtained data were compared with facts in known literature. By the isolated alkaloid was determined its cholinesterase inhibitory activity against acetylcholinesterase and butyrylcholinesterase. Its inhibitory activity was expressed as IC50 (M) and compared with known standards galanthamine, physostigmine, and Huperzine A. This alkaloid is inactive against cholinesterase (IC50 AChE > 1000 M, IC50 BChE > 1000 M). On the basis of gained results, we can evaluate this alkaloid from the point of view of cholinesterase inhibition as potentially unusable in the treatment of AD. Key...
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Study of biological activity of isolated alkaloids from Argemone grandiflora (Papaveraceae)I.
Adamcová, Markéta ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Adamcová, M.: Study of biological activity of alkaloids isolated from Argemone grandiflora (Papaveraceae) I. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2015. The aim of this study was isolation of substances from total diethyl ether alkaloid extract of Argemone grandiflora Sweet, their identification and assessment of their inhibition activity towards acetylcholinesterase, butyrylcholinesterase and prolyl oligopeptidase. Using common chromatografic methods, four alkaloids were isolated, that was identified as (+)-laudanosine, protopine, (-)-argemonine a (-)-platycerine. These substances was tested for their inhibition activity IC50: (+)-laudanosine (IC50 AChE = 617,00 ± 46,55 μM, IC50 BuChE = 644,77 ± 55,52 μM, IC50 POP = not mesured yet); protopine (IC50 AChE = 229,98 ± 21,02 μM, IC50 BuChE = 208,87 ± 17,67 μM, IC50 POP ˃ 1000 μM); (-)-argemonine (IC50 AChE = 4677,75 ± 1241,08 μM, IC50 BuChE = 885,45 ± 119,50 μM, IC50 POP = 337 ± 83,1 μM); (-)-platycerine (IC50 AChE = 223,65 ± 19,61 μM, IC50 BuChE = 1651,25 ± 327,7 μM, IC50 POP = 687 ± 74 μM). In comparison with the standards galanthamine (IC50 AChE = 1,710 ± 0,065 μM, IC50 BuChE = 42,30 ± 1,30 μM) and huperzine A (IC50 AChE = 0,033 ± 0,001...
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