Nicotinic acetylcholine receptors are ligand-gated ion channels which are located on neuromuscular junction and in central and perifric nervous system. Activity of nicotinic receptor might be modulated by variety of pharmacological agents. In this work, we have focused on the study of the inhibition effect of tacrine and its derivatives on the nicotinic acetycholine receptors of muscle and neuronal type. These derivatives function as acetylcholinesterase inhibitors and also interact with nicotinic acetylcholine receptors. The majority of current forms of treatment of Alzheimer's disease is based on cholinesterase inhibitors. We have studied the mechanism of tacrine and its derivatives by using patch clamp method in the configuration of whole-cell recording. Powered by TCPDF (www.tcpdf.org)

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jana Kucková Supervisor: PharmDr. Marie Vopršalová, CSc. Title of diploma thesis: Testing antioxidant properties of selected acetylcholinesterase inhibitors Very widespread Alzheimer's disease is typical by a complex pathology. Its causality is not clearly understood. There is increasing discussion due to the negative impact of free radicals on this disease formation. There are testing new substances that have also antioxidant properties, in addition to their classical effects. The aim of this diploma thesis is spectrophotometric testing of antioxidant properties of selected acetylcholinesterase inhibitors. It is based on DPPH test where the presence of antioxidants with antiradical activity causes the reduction of the color stable 2,2-diphenyl-1- picrylhydrazyl (DPPH) radical to a colorless molecule. The principle of the method is the measurement of decrease in absorbance (decolorization) of selected substances that are directly proportional to the antioxidant (antiradical) efficacy of the analyzed inhibitors. It focuses on twelve samples, Phenothiazine, which is the leader structure of new inhibitors synthesis, and two standards. Antioxidant activity is expressed as the effective...

Miklová V.: Cytotoxic and cholinesterase inhibitory activity of extracts from selected species of the Centaurea L. genus II. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové, 2020. This Diploma Thesis was carried out at the Department of Pharmaceutical Botany FAF UK and it is a part of a screening of biologically active secondary metabolites of selected on taxa of the genera Centaurea L. and Psephellus L. in the family Asteraceae. Secondary metabolites are responsible for various effects on the human body. The study is focused on the phytochemical research of extracts prepared from aerial parts (cauloms with leaves) of Centaurea cyanus L., Centaurea stoebe L., Cyanus montanus (L.) Hill, Centaurea benedicta L., Centaurea jacea L., Centaurea macrocephala Muss. Puschk. ex. Willd, Centaurea solstitialis L., Centaurea nigra L., Centaurea scabiosa L., Psephellus bellus (Trautv.) Wagenitz, Centaurea pannonica (Heuff.) Hayek and Psephellus dealbatus (Willd) K. Koch. Both ethyl acetate and summary ethanolic extracts were prepared for detection of individual groups of secondary metabolites by thin-layer chromatohraphy. Consistently with previously published results, sesquiterpenes, flavonoids, coumarins, phenolic compounds,...

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...

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...

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.

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)....

Trimethyltin (TMT) is known to produce substantial damage to the hippocampal formation. It also destroys neurons within the entorhinal cortex, thereby causing degeneration of perforant path afferents that terminate in the outer molecular layer (OML) of the dentate gyrus. Surgical destruction of the entorhinal cortex also causes the perforant path to degenerate. This leads to reactive synpatogenesis (axonal sprouting) of septal afferents to the dentate gyrus. The purpose of the present study was to determine whether administration of 6 mg/kg of TMT by gavage to rats would cause axonal sprouting within the septodentate projection. A histochemical stain for acetycholinesterase (AChE) was used. Compared to control subjects rats given TMT exhibited significantly denser AChE staining in the dentate OML. This is putative indication of reactive synaptogenesis within the cholinergic projection to this layer of the dentate and is somewhat surprising because other neurotoxins, such as lead and ethanol, that affect neurons within the hippocampal formation reduce the capacity for reactive synaptogenesis in response to lesions of the entorhinal cortex.

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