|
|
Natural products and their β-secretase inhibitory activity.
Kočová, Kateřina ; Chlebek, Jakub (advisor) ; Macáková, Kateřina (referee)
Kočová, K.: Natural compounds and their β-secretase inhibitory activity, Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradci Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2015, 83 p. Data used in this Diploma Thesis have been taken from foreigner scientific literature. It provides the whole summary of natural compounds with β-secretase inhibitory activity. First chapter Alzheimer's disease briefly describes a definition, risk factors and symptomatology of the disease. Most of this chapter characterizes an etiopathology of the disease focused on amyloid theory. Finally there are also mentioned current approaches to therapy of Alzheimer's disease and those, which stay in clinical trials. Next part is dedicated to physiological functions and substrates of the β-secretase. This diploma thesis evaluates the current state of scientific research of synthetic inhibitors of β-secretase, describes the most important methods of testing inhibition and activity of β-secretase in vitro and outlines the issue of development of new inhibitors using in silico method. Main part of this work consists of the list of natural compounds with β- secretase inhibitory activity. This part is structured according to particular types of primary and secondary metabolites....
|
|
|
Biological activity of plant metabolites XXII. Alkaloids of Papaver somniferum L. and their activity against human cholinesterases.
Daněk, Jiří ; Opletal, Lubomír (advisor) ; Chlebek, Jakub (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Jiří Daněk Consultant: prof. RNDr. Lubomír Opletal, CSc. Title of Thesis: Biological activity of plant metabolites XXII. Alkaloids of Papaver somniferum L. and their activity against human cholinesterases. During the screening of certain plant species for alkaloids with antioxidant activity and inhibition activity against human cholinesterases was studied opium poppy (Papaver somniferum L.). The basic extract was prepared from 7,0 kg of dry green poppy capsules percolated by 78 litres of ethanol. This extract was gradually alkalizated and individual extracts of each alkaloid type were prepared. In this thesis only the etheric extract was processed. It was divided gradually depending of the pH to several individual alkaloid fractions. Only the ADd fraction, containing chlorides insolubile in CHCl3 and bases solubile in CHCl3, was divided into individual alkaloids using the thin layer chromatography. One of the isolated alkaloids was codeine, which was indetified by mass spectroscopy, melting point and direct comparsion with standart. Codeine has the antioxidant activity EC50 >500 µM, inhibition activity agains human erythrocyte AChE IC50 = 3320 µM, inhibition activity against...
|
|
|
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...
|
|
|
Biological activity of plant metabolites XXVIII. Alkaloids from selected cultivars of Narcissus cyclamineus REDOUTÉ and their influence on acetylcholinesterase and butyrylcholinesterase
Janura, Michal ; Opletal, Lubomír (advisor) ; Chlebek, Jakub (referee)
Biological activity of plant metabolites XXVIII. Alkaloids from selected cultivars of Narcissus cyclamineus REDOUTÉ and their influence on acetylcholinesterase and butyrylcholinesterase. JANURA M.: Diploma work, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2015, Czech Republic. Abstract: The summary extracts of alkaloids from bulbs of N. cyclamineus esp. N. cyclamineus cv. Jenny, N. cyclamineus cv. Little Witch, N. cyclamineus cv. Rapture, N. cyclamineus cv. Surfside, N. cyclamineus cv. Peeping Tom, N. cyclamineus cv. Warbeld and N. cyclamineus cv. Skater's Waltz were obtained by the procedures common for this type of compounds. The alkaloid extracts were analyzed by GC/MS and the probable occurrence of individual alkaloid substances was observed. These extracts were also assayed for HuAChE and HuBuChE inhibitory activity. N. cyclamineus cv. Surfside with IC50 = 61,26 ± 6,42 µg/ml and N. cyclamineus cv. Warbeld with IC50 = 85,43 ± 11,13 µg/ml have the best results in inhibition of HuBuChE. The best inhibitory activity on HuAChE has N. cyclamineus cv. Warbeld with IC50 (HuAChE) = 36,82 ± 4,50 µg/ml. Key words: Narcissus, Acetylcholinesterase, Butyrylcholinesterase, GC/MS, Alzheimer's disease.
|
|
|
Nutraceuticals 5. Compouds usable as an adjuvant in the treatment of Alzheimer's disease.
Nejedlý, Josef ; Opletal, Lubomír (advisor) ; Chlebek, Jakub (referee)
Nejedly, J.: Nutraceuticals 5. Compounds usable as an adjuvant in the treatment of Alzheimer's disease. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Department of Pharmaceutical Botany and Ecology, Hradec Kralove 2014, 102 p. This literature review, dealing with the pathophysiology of Alzheimer's disease and possible use of nutraceutical products as an adjuvant in the therapy of the disease, has been done by analysis of foreign and domestic literature. In the chapter Alzheimer's disease, various pathological processes, leading to the development of the disease and also risk factors, clinical picture and a brief indications of currently used treatment, were introduced. The main part of thesis called Nutraceuticals has introduced a comprehensive overview and categorization of compounds (plant extracts) which can be used in influencing of Alzheimer's disease by the mechanism of action. In the chapter Nutraceuticals in Czech Republic, various product and suplements were listed, which are available on the market in Czech Republic and could be used as an adjuvant in the therapy of Alzheimer's disease. Finally, it was shown the evaluation (pros, cons, potential interaction) of substances and supplements, which have been state in the thesis, with a proposal for their...
|
|
|
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...
|
|
|
Biological aktivity of secondary plants metabolites I. Alkaloids of Narcissus jonquilla L.
Nováková, Dana ; Ločárek, Miroslav (advisor) ; Chlebek, Jakub (referee)
Nováková D.: Biological activity of secondary plants metabolites I. 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. 70. 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 (Sundial, Sundisc, Sweetness, Waterperry, Simplex, Twinkling Yellow, Yazz) were studied with respect to their acetylcholinesterase (HuAChE) and butyrylcholinesterase (HuBuChE) inhibitory activity and alkaloid patterns. Twenty-three alkaloids were determined by GC/MS, and ten of them identified from their mass spectra and retention times. All samples exhibited content of galanthamine, most samples contained lycorine and tazettine. Promising HuAChE inhibition activity was demonstrated by Narcissus jonquilla L. cv. Waterperry with IC50 values of 6.53 ± 0.88 μg/mL. The strongest inhibitory activity against HuBuChE was detected in extract from Narcissus jonquilla L. cv. Sundisc with IC50 value of 5.09 ± 0.64 μg/mL. Keywords: Alzheimer's disease, Amaryllidaceae, Narcissus,...
|
|
|
Biological activity of plant metabolites XXIV. Influence of alkaloids from some species of the genus Fritillaria L. on activity of acetylcholinesterase and butyrylcholinesterase.
Mervartová, Markéta ; Opletal, Lubomír (advisor) ; Chlebek, Jakub (referee)
Mervartová, M.: Biological activity of plant metabolites XXIV. Influence of alkaloids from some species of the genus Fritillaria L. on activity of acetylcholinesterase and butyrylcholinesterase. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical botany and Ecology, Hradec Králové 2013, 60 s. Biological activity of extracts to human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was carried out. Extracts were prepared from ten chosen species of the genus Fritillaria which could be perspective for the treatment of Alzheimer's disease: F. camtschatcensis (bulb), F. eduardii (bulb), F. elwesii (bulb), F. graeca (bulb), F. hermonis var. amana (bulb), F. imperialis (herb), F. meleagris var. alba (bulb), F. michailovskyi (bulb), F. minuta (bulb), F. ussuriensis (bulb). Sumary (ethanol) and alkaloidal (ethylacetate) extract were prepared from each sample. The sumary extract was obtained by extraction of pulverized drug by 95% ethanol. The alkaloidal extract was made by following dissolution in 2% H2SO4, filtration, alkalization by 10% Na2CO3 on pH approx. 10 and final extraction of alkaloidal bases into ethylacetate. The inhibitory activity of these extracts to human AChE (from red blood cells) and BuChE (from plasma) was...
|
|
|
Study of biological activity of isolated alkaloids from Corydalis cava (Fumariaceae)
Chlebek, Jakub ; Opletal, Lubomír (advisor) ; Drašar, Pavel (referee) ; Kuča, Kamil (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Mgr. Jakub Chlebek Supervisor: Doc. RNDr. Lubomír Opletal, CSc. Title of Doctoral Thesis: Study of biological activity of isolated alkaloids from Corydalis cava (Fumariaceae). Key words: Corydalis cava, isoquinoline alkaloids, DPPH, AChE, BuChE, BACE1, IMER. Tubers of Corydalis cava were selected on the basis of bio-guided spectrophotometric Ellman's method as a source of isoquinoline alkaloids for study of their selected biological activities. The tubers of Corydalis cava were extracted with ethanol and the mixture of summary tertiary alkaloids (fraction A) was fractionated in silica gel chromatography column using step gradient elution with hexane, chloroform and ethanol. Repeated column chromatography, preparative TLC and crystallization led to the isolation of fifteen isoquinoline alkaloids. The chemical structures of isolated compounds were determined on the basis of spectroscopic techniques and by comparison with literature data. Isolated alkaloids were tested on ability to inhibit AChE, serum BuChE (IC50), BACE1 and for its free-radical scavenging activity (EC50). The cholinesterase inhibitory activity was determined in vitro by modified spectrophotometric Ellman's...
|
|
|
Pharmacognostic study of Alnus spp.
Chlebek, Jakub ; Jahodář, Luděk (advisor) ; Karlíčková, Jana (referee)
Charles Univerzity in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Degree work term: Pharrnacognostic study of Alnus spp. Student: Jakub Chlebek Abstract The degree work Pharmacognostic study of radix Alnus spp. consists of theoretical and experimental part. Theoretical part contains botanical characteristic of the three home species of Czech Republic (Alnus glutinosa, Alnus incana, Alnus rugosa), phytochemical review of the compounds of the genus Alnus and their biological acivities. Experimental part deals with phytochemical and biological study of the roots of Alnus glutinosa. Dried roots of the black alder (Alnus glutinosa) were extracted with Me2CO-H2O (7:3). Final extract was chromatographed over test silica gel colum using a MeOH- CHCl3 gradient (0, 1, 2, 4, 8, 16, 32, 100 %). Elution gave 36 fractions. All the separations were analysed by TLC (hexane-EtOAc MeOH, 2:2:1). The sterols were detected in the fraction No. 7 by TLC, melting point and GC-MS. Major present sterols were β-sitosterol, β-sitostanol, minor sterols campestanol, campesterol. Fractions No. 10 and 19 were analysed by HPLC. Antioxidant activity of the fraction No. 19 was measured with DPPH radical and was low (EC50 0.32 mg/mL). Test silica gel colum experience were used in analysis on...
|
guest ::
