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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. 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 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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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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Biological activity of plants secondary metabolites XXX. Basic search of selected taxons on anticholinesterase activity.
Karaščáková, Diana ; Opletal, Lubomír (advisor) ; Hošťálková, Anna (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Diana Karaščáková Supervisor: prof. RNDr. Lubomír Opletal, CSc. Title of diploma thesis: Biological activity of plants secondary metabolites XXX.; Basic search of selected taxons on anticholinesterase activity As part of the study of the biological activity of secondary metabolites, 7 taxa of higher plants were selected. The study deals with basic research of summary and alkaloid extracts prepared from morphological parts of plants Annona muricata (leaves), Leonotis leonurus (perch), Turnera diffusa (perch), Hamelia patens (perch), Uncaria guianensis (bark), Allamanda cathartica (perch) and Morinda citrifolia (leaves). To elucidate the presence of the major types of secondary metabolites, extracts were prepared and subjected to detection reactions by TLC using ten detection reagents. After detection by Dragendorff's reagent of ethyl acetate extracts, alkaloids were significantly present only in Annona muricata. Alkaloids were not detected in the bark of Uncaria guianensis. Using the Ellman method, the extracts were tested for potential inhibitory activity against human brain cholinesterases, using both recombinant enzymes. No significant active substances were present in any of the measured...
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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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Vinca minor L. alkaloids and their biological activity VIII.
Hojgrová, Veronika ; Chlebek, Jakub (advisor) ; Šafratová, Marcela (referee)
V. Hojgrová: Alkaloids of Vinca minor L. and their biological activity VIII. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany. Number of pages 69. This diploma thesis deals with the isolation of alkaloids from Vinca minor L. from the family Apocynaceae. Separation of alkaloids from the selected fraction (VM 215-258) or from their subfractions (VM 34-41, VM 86, VM 87-113) was performed by preparative TLC. Two pure alkaloids were isolated from the subfraction (VH 34-41). The first VH-1 alkaloid not yet isolated and the second VH 2 alkaloid: (-)-raucubainin. Alkaloids were identified by EI-MS, LC-MS, NMR and optical rotation and were compared with data in the literature. Isolated alkaloids were tested for acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and prolyloligopeptidase (POP) inhibitory activity and for cytotoxicity. Both substances did not show significant cholinesterase inhibitory activity IC50 against AChE after measurement, only (-)-raucubainin showed a slight activity against BuChE (IC50 = 94 ± 7 μM), VH-1 was found to be inactive (IC50 > 100 μM). POP inhibitory activity has so far only been tested for (-)-raucubainin; was found to be inactive (IC50 > 1000 µM). The results of the cytotoxic activity of the alkaloids...
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Vinca minor L. alkaloids and their biological activity II.
Pavuková, Simona ; Chlebek, Jakub (advisor) ; Hradiská Breiterová, Kateřina (referee)
Pavuková, S.:Vinca minor L. alkaloids and their biological activity II. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové 2020. Vinca minor L. is a species of species of flowering plant, native mainly to central and southern Europe, which containst more than 50 indole alkaloids. During screening of potential plant inhibitors against human acetylcholinesterase (hAChE) and butyrylcholinesterase (HBChE) at our department, an alkaloidal extract from dried aerial parts of Vinca minor demonstrated strong and selective hBChE inhibitory activity with an IC50 value of 13.60 ± 0.83 μg/mL, however, against hAChE was inactive (IC50 value >100 μg/mL). The fraction VM 323 - 327 (4,72 g) was separated by column chromatography on silica gel again with stepwise elution by using chloroform and ethanol and overall 7 joined fractions were obtained.Subsequently, repeated preparative TLC on silica gel led to isolation of three compounds; the newly isolated substance SP-1, (-)-picrinine (SP-2) and deacetylakuammiline (SP-3). Their structures were elucidated with mass spectrometry (ESI), NMR and optical rotation. Isolated alkaloids were tested on ability to inhibit AChE, BuChE, POP a GSK-3β, which are enzymes playing an important role in...
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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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Biological activity of plants secondary metabolites XXX. Basic search of selected taxons on anticholinesterase activity.
Karaščáková, Diana ; Opletal, Lubomír (advisor) ; Hošťálková, Anna (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Diana Karaščáková Supervisor: prof. RNDr. Lubomír Opletal, CSc. Title of diploma thesis: Biological activity of plants secondary metabolites XXX.; Basic search of selected taxons on anticholinesterase activity As part of the study of the biological activity of secondary metabolites, 7 taxa of higher plants were selected. The study deals with basic research of summary and alkaloid extracts prepared from morphological parts of plants Annona muricata (leaves), Leonotis leonurus (perch), Turnera diffusa (perch), Hamelia patens (perch), Uncaria guianensis (bark), Allamanda cathartica (perch) and Morinda citrifolia (leaves). To elucidate the presence of the major types of secondary metabolites, extracts were prepared and subjected to detection reactions by TLC using ten detection reagents. After detection by Dragendorff's reagent of ethyl acetate extracts, alkaloids were significantly present only in Annona muricata. Alkaloids were not detected in the bark of Uncaria guianensis. Using the Ellman method, the extracts were tested for potential inhibitory activity against human brain cholinesterases, using both recombinant enzymes. No significant active substances were present in any of the measured...
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