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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) ; 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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Centaurea cyanus L. (Asteraceae) alkaloids and their biological activity related to Alzheimer's disease
Drabbová, Adriana ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
Drabbová, A.: Title of Diploma Thesis: Centaurea cyanus L. (Asteraceae) alkaloids and their biological activity related to Alzheimer's disease. Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové 2020. Ethyl acetate and chloroform alkaloids extracts were prepared from Centaurea cyanus L. seeds. A novel alkaloid AD-1 (Adrabbin) was isolated from the ethyl acetate extract by common chromatografic methods (column chromatography, preparative TLC). Its structure was elucidated by mass spektrometry, NMR analysis and determination of optical rotation. The alkaloid AD-1 (Adrabbin) possesses a unique structure which consists of a cyclic indole moiety. Also LC-MS analysis of fractions obtained by flash chromatography was performed. In those fractions were detected molecular ions related to compounds previously isolated from other Centaurea species. Alkaloid AD-1 (Adrabbin) was tested on ability to inhibit human cholinesterases, prolyl oligopeptidase and gylcogen synthase kinase 3β. The compound was considered against human cholinesterases inactive (IC50 values > 100 µM). Interestibgly, the alkaloid inhibited prolyl oligopeptidase the same intensity as a standard berberine (AD-1: IC50 143,0 ± 6,0 µM; berberin: IC50 142,0 ± 21,0 µM). The novel compound...
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Vinca minor L. alkaloids and their biological activity I.
Jurkaninová, Martina ; Chlebek, Jakub (advisor) ; Opletal, Lubomír (referee)
1 9 ABSTRACT Jurkaninová, M.: Vinca minor L. alkaloids and their biological activity I. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové, 2019 The aim of this thesis was the isolation of alkaloids from selected fraction 3 (joined fractions (15 - 36), which was a sub-fraction of the fraction VM 323 - 327. It was obtained from the previous processing of an alkaloidal extract from the Vinca minor L at the Department of Pharmaceutical Botany as a part of elaboration of diploma thesis of Aneta Vítavcová.[78] The fraction VM 323-327 was separated by column chromatography on silica gel and a totally, of 7 subfractions were obtained. Subsequent repeated processing of the selected sub-fraction 3 (15 - 36) by preparative TLC on silica gel resulted in the isolation of (-)-vinoxine and its racemate (±)-vinoxine. Identification of their structure was determined based on MS, NMR and optical rotation. The inhibitory activity against acetylcholinesterase, butyrylcholiesterase and prolyl oligopeptidase were determined for the isolated substances. Inhibitory activity against selected enzymes was measured by spectrophotometric methods. Isolated alkaloids were required to be inactive against AChE and POP (IC50 >1000 μM), against to BChE showed a...
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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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