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Isolation of alkaloids of the species Geissospermum vellosii Allemão and study of their biological activity VI.
Váňová, Lucie ; Šafratová, Marcela (advisor) ; Chlebek, Jakub (referee)
Lucie Váňová: Isolation of alkaloids of the species Geissospermum vellosii Allemão and study of their biological activity IV. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacognosy and Pharmaceutical Botany, Hradec Králové 2022. Key words: bark, Geissospermum vellosii Allemão, alkaloids, preparative TLC, GC-MS, NMR, (+)-19,20-dehydrotubifolidine, aspidolimidine, geissoreticulatine, inhibition activity, AChE, BuChE, Alzheimer's disease The aim of this diploma thesis was the isolation of at least 3 alkaloids in pure form from the GV-5 fraction, which was extracted from the bark of the South American tree Geissospermum vellosii Allemão. By using preparative thin layer chromatography (TLC), 9 subfracions (GV-5-A až GV-5-I) were acquired from this fraction. Those that were of sufficient mass were subsequently subjected to further division. Three alkaloids in pure form were isolated through purification using preparative TLC: GV-5-B-3-A, GV-5-C-4-C, GV-5-C-2-B-1. Gained active substances from this plant were analyzed by gas chromatography- mass spektrometry (GC-MS) and nuclear magnetic resonance (NMR). By comparing the obtained alcaloid's spectra with available data and literature, those alkaloids were identified as: (+)-19,20-dehydrotubifolidine...
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Screening of biological activity of various species of the genus Narcissus sp. I
Komendová, Karolína ; Suchánková, Daniela (advisor) ; Chlebek, Jakub (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical botany Candidate: Karolína Komendová Supervisor: PharmDr. Daniela Hulcová, Ph.D. Title of thesis: Screening of biological activity of various species of the genus Narcissus sp. I Key words: Amaryllidaceae, Narcissus, alkaloids, AChE, BuChE, Alzheimer's disease Alkaloids from family Amaryllidaceae (AA) nowadays belong to the most important and also the most examined alkaloids. This is because of their structural diversity and a broad spectrum of biological effects. The main aim of my diploma was to prepare whole bulb extracts from seven different cultivated varieties of genus Narcissus and to select those with the highest potential to inhibit enzyme acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Inhibition of these enzymes is very important in the treatment of Alzheimer's disease (AD). Summary extracts were obtained from these cultivars: N. cv, Apotheose (AL - 718), N. cv. Chromacolor (AL - 722), N. cv. Hungarian Rhapsody (AL - 729), N. cv. Mon Cheri (AL - 736), N. cv. Peach Cobbler (AL - 738), N. cv. Pink Pride (AL - 740) a N. cv. Red Devon (AL - 742). The isolated extracts were subsequently analyzed by GC-MS. The following alkaloids were found in the majority of extracts:...
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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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Biological activity of Peganum harmala L. alkaloids and their semi-synthetic derivatives I.
Víchová, Barbora ; Chlebek, Jakub (advisor) ; Křoustková, Jana (referee)
1 ABSTRACT Víchová Barbora: Biological activity of Peganum harmala L. alkaloids and their semi-synthetic derivatives I. Diploma thesis 2022. Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany β-Carboline alkaloids are natural substances with potential use in tumor therapy. In particular harmine, which acts cytotoxically by several mechanisms. The aim of the diploma thesis was to prepare N9-derivatives of harmine derivatives, to clarify their structure based on common spectrometric and spectroscopic methods (ESI, ESI-MS, NMR) and subsequently to study their biological activity (cytotoxicity, AChE, BchE and GSk-3beta inhibition). These tests resulted in several active derivatives, suitable candidates for further study. 9-N-(2-nitrobenzyl)harmine (HMA-22) was significantly cytotoxic to the Jurkat cell line (16% cell viability after 48 hours, compared to the control, with better cytotoxicity than the standard doxorubicin at a concentration of 1 μM). Another very active derivative was found 9-N-(5-bromopentyl)harmine (HMA-30), which was more cytotoxic to most tested cell lines than doxorubicin (1 μM), similarly as most of other derivatives. HMA-30 was also found as a potent BChE inhibitor (IC 50 4.06 ± 0.48 μM). 9-N-(4-nitrobenzyl)harmine (HMA-20)...
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Biological activity of Peganum harmala L. alkaloids and their semi-synthetic derivatives II.
Fejtková, Martina ; Chlebek, Jakub (advisor) ; Cahlíková, Lucie (referee)
Fejtková Martina: Biological activity of Peganum harmala L. alkaloids and their semi-synthetic derivatives II. Diploma thesis 2022. Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacognosy und Pharmaceutical botany. This diploma thesis deals with the preparation of semi-synthetic derivatives of the alkaloid harmine and the study of their biological activity. The alkaloid harmine was isolated by preparative TLC from an alkaloid extract, exactly from its subfraction PH-F1. Semi-synthetic derivatives were prepared by incorporation of different substituents in the N9 position of harmine. For the purposes of this diploma thesis were prepared 17 derivatives, which were subsequently identified on the basis of LC-MS, ESI-HRMS and NMR analysis. After structural elucidation of prepared derivatives, their biological activity was studied. The prepared substances were tested for their inhibitory effect on human acetylcholinesterase (AChE), human butyrylcholinesterase (BuChE), glykogen synthase kinase 3β (GSK-3β) and their cytotoxic activity was also measured on selected tumor and leukemia lines and one healthy cell line. Some of the prepared derivatives showed interesting selective inhibitory potencial against human BuChE, the most active derivative was...
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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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Isolation of alkaloids of the species Geissospermum vellosii Allemão and study of their biological activity VI.
Váňová, Lucie ; Šafratová, Marcela (advisor) ; Chlebek, Jakub (referee)
Lucie Váňová: Isolation of alkaloids of the species Geissospermum vellosii Allemão and study of their biological activity IV. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacognosy and Pharmaceutical Botany, Hradec Králové 2022. Key words: bark, Geissospermum vellosii Allemão, alkaloids, preparative TLC, GC-MS, NMR, (+)-19,20-dehydrotubifolidine, aspidolimidine, geissoreticulatine, inhibition activity, AChE, BuChE, Alzheimer's disease The aim of this diploma thesis was the isolation of at least 3 alkaloids in pure form from the GV-5 fraction, which was extracted from the bark of the South American tree Geissospermum vellosii Allemão. By using preparative thin layer chromatography (TLC), 9 subfracions (GV-5-A až GV-5-I) were acquired from this fraction. Those that were of sufficient mass were subsequently subjected to further division. Three alkaloids in pure form were isolated through purification using preparative TLC: GV-5-B-3-A, GV-5-C-4-C, GV-5-C-2-B-1. Gained active substances from this plant were analyzed by gas chromatography- mass spektrometry (GC-MS) and nuclear magnetic resonance (NMR). By comparing the obtained alcaloid's spectra with available data and literature, those alkaloids were identified as: (+)-19,20-dehydrotubifolidine...
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Screening of selected alkaloids of Fumariaceae and Amaryllidaceae families on Farnesoid X receptor and the G protein-coupled bile acid receptor 1
Hutníková, Miriama ; Pávek, Petr (advisor) ; Chlebek, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Miriama Hutníková Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of diploma thesis: Screening of selected alkaloids of Fumariaceae and Amaryllidaceae families on the farnesoid X receptor and the G protein coupled receptor 1 Farnesoid X receptor (FXR) and bile acid receptor associated with G protein 1 (TGR5) significantly affect metabolic processes in the human body. The role of FXR in neuronal apoptosis in Alzheimer's disease (AD) has also been discovered. The possible structural similarity of the small lipophilic molecules binding to these receptors and the alkaloids found in the plants Corydalis cava and Narcissus pseudonarcissus, as well as the richoften use of these plants in traditional medicine, represent a potential therapeutic intervention for these molecules. In our screening methods, we performed tests using a luciferase gene reporter assay to determine the ability of the alkaloids to interact with FXR and TGR5 in the HepG2 cell line. Many derivatives have shown a strong ability to antagonize FXR and TGR5 activated by obethicholic (OCA) or litocholic (LCA) acids in this assay. Some of the compounds also demonstrated the ability to potentiate the effects of OCA or LCA. Cytotoxicity...
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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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