|
|
Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors II
Králová, Kristýna ; Cahlíková, Lucie (advisor) ; Kučera, Tomáš (referee)
CHARLES UNIVERSITY FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACOGNOSY AND PHARMACEUTICAL BOTANY CANDIDATE: Kristýna Králová SUPERVISOR: prof. Ing. Lucie Cahlíková, Ph.D. CONSULTANT: Mgr. Filip Pidaný TITLE OF DIPLOMA THESIS: Amaryllidaceae alkaloids as inspiration of preparation of selective butyrylcholinesterase II Plants of the family Amaryllidaceae are an important source of biologically active substances, which are labeled as Amaryllidaceae alkaloids (AAs). These natural products show a wide range of biological characteristics, for which they are also intensively studied. Their significant biological effects include antiviral, antibacterial, antifungal, anti-inflammatory, antiparasitic, and cytotoxic activity. Their other important characteristic is the ability to inhibit both cholinesterases: acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Inhibition of AChE is used in the therapy of Alzheimer's disease (AD). Currently, in the treatment of the symptoms of this disease, one AA, galanthamine, is used. Recently a new structural type of AAs, carltonins, have been isolated from the plant Narcissus pseudonarcissus cv. Carlton. These substances showed a significant inhibitory effect against BuChE and became the inspiration for the synthesis of selective BuChE inhibitors....
|
|
|
Synthesis of Ortho-Condensed Nitrogen Heterocycles Using Gold Complexes
Makaj, Petr ; Matouš, Petr (advisor) ; Kuneš, Jiří (referee)
5 ABSTRACT Charles University, Faculty of Pharmacy in Hradci Králové Department of Organic and Bioorganic Chemistry Candidate: Petr Makaj Supervisor: PharmDr. Petr Matouš, Ph.D Title of Thesis: Synthesis of Ortho-Condensed Nitrogen Heterocycles Using Gold Complexes This diploma thesis is focused on the preparation of pyridopyridine derivatives using gold-catalyzed cyclizations. The synthesis is based on MBS-protected propargylamine, which after substitution with aryl using Sonogashira coupling reacts with tert-butyl (3- oxopent-4-ynyl)carbamate to form substituted 1,5-enyne. The enyne thus prepared then undergoes cycloisomerization using tris(2- furanyl)phosphinegold(I)chloride as a catalyst to form pyridopyridine. Substances with this scaffold can be further used to synthesize potentially biologically active structures. Keywords: gold catalysis, cyclization, pyridopyridine derivatives, 1,8-naphthyridine derivatives
|
|
|
Derivatives of Amaryllidaceae alkaloids as potential drugs in the treatment of tumor diseases
Valachová, Iva ; Suchánková, Daniela (advisor) ; Kučera, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy Candidate: Iva Valachová Supervisor: Pharm.Dr. Daniela Hulcová, Ph.D. Title of diploma thesis: Derivatives of Amaryllidaceae alkaloids as potential drugs in the treatment of tumor diseases Twelve aromatic derivatives were prepared. The substitutions were performed on the hydroxyl group at C-3. This was acylated with differently substituted benzoyl chlorides affording the corresponding esters. Structural identification was performed by 1D- and 2D- NMR, ESI-HRMS spectroscopic techniques and optical rotation measurement. The yield of all reactions was more than 60 %. After converting these derivatives to hydrochlorides, their biological activity was tested. The Amaryllidaceae alkaloid vittaine itself exhibits cytotoxic activity and therefore its derivatives have been investigated in this respect. It has been tested against 9 cancerous and 1 non-cancerous cell lines. 3-O-(4-Chloro-3-nitrobenzoyl)vittatine showed the highest cytotoxic activity, unfortunatelly, it does not selectively affect only cancerous cells. Conversely, 3-O-(2-naphthoyl)vittatine has a selective effect on the HT-29 cancerous cell line (colorectal carcinoma) with a viability value of 32 ± 3 %, potentially being the subject of further studies of cytotoxicity...
|
|
|
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...
|
|
|
Amaryllidaceae alkaloids of montanine type and their derivatives as potential drugs.
Maafi, Negar ; Cahlíková, Lucie (advisor) ; Šmejkal, Karel (referee) ; Havlík, Jaroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: Negar Maafi Supervisor: Prof. Ing. Lucie Cahlíková, Ph.D. Title of Doctoral Thesis: Amaryllidaceae alkaloids of montanine type and their derivatives as potential drugs. Based on the knowledge of the biological activity of montanine-type alkaloids of Amaryllidaceae, these alkaloids were selected for the preparation of their semisynthetic derivatives to study the relationship between structure and the activity. Derivatives of montanine-type alkaloids were prepared using haemanthamine and montanine as starting substances. The montanine-type alkaloid 3-O- methylpancracine was prepared using intramolecular rearrangement of haemanthamine. Previously isolated montanine from bulbs of Hippeastrum x hybridum cv. Ferrari was used in synthesize of derivatives. In total, more than 80 aliphatic and aromatic derivatives of montanine and 3-O- methylpancracine have been prepared. All compounds were identified using 1D- and 2D-NMR, MS, HRMS, and so forth. The prepared derivatives were screened for a wide range of biological activities (inhibitory potential against hAChE/hBuChE, antimycobacterial, antibacterial and antifungal activity, cytotoxicity, and others). In the hAChE/hBuChE study, the...
|
|
|
Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I
Wisura, Matěj ; Cahlíková, Lucie (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Matěj Wisura Supervisor: prof. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I The Amaryllidaceae family is considered to be very important source of biologicaly active natural compounds, alkaloids. These compounds are intensively studied because of their antiviral, antifungal, antiparasitic, antioxidative and antiinflammatory properties and especially for their ability to inhibit cholinesterases. This source is still not entirely depleted, which is proved by recent isolation of utterly new structural type of Amaryllidaceae alkaloids, carltonines, isolated form Narcissus pseudonarcissus cv. Carlton. Carltonines have shown promissing inhibitory activity of BuChE. Isolation of carltonines has become an inspiration for synthesis of highly selective BuChE inhibitors based on norbelladine structural type. This diploma thesis proceeds from pilot series of 20 compounds. During this study, another 21 compounds were prepared, expanding the portfolio and knowledge of structure-activity relationships within selective BuChE inhibitors group. Generated compounds were identified using NMR and ESI-HRMS....
|
|
|
Alkaloids of Narcissus species cultivars and their biological activity III.
Kahovcová, Anna ; Hradiská Breiterová, Kateřina (advisor) ; Suchánková, Daniela (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmacognosy and Pharmaceutical Botany Author: Kahovcová Anna Supervisor: PharmDr. Kateřina Hradiská Breiterová, PhD. Title of thesis: Alkaloids of Narcissus species cultivars and their biological activity III. Key words: Narcissus, alkaloids, biological activity, Alzheimer's disease, cytotoxicity The most important aim of this diploma thesis was to prepare summary alkaloid extracts from bulbs of the genus Narcissus L., specifically from seven cultivars Narcissus cv. MONDRAGON, RIP VAN WINKLE, SAGITTA, CHEERFULNESS, DOUBLE FASHION, PRECOCIOUS and FLOWER DRIFT, which were labeled as AL-458, AL-575, AL-443, AL-466, AL-549, AL-545 a AL-546. Samples were subsequently prepared for GC-MS analysis and screening determination of biological activities, namely the ability to inhibit human cholinesterases hAChE and hBuChE and cytotoxicity from these extracts. Using GC-MS analysis a total of 20 alkaloids were identified by comparing their mass spektra with the literature or the NIST library. Identified alkaloids include lycorine, lycoramine, lycoraminone, anhydrolycorine, pankracine, caranine, O-acetyllycorine, pluvine, norpluvine, assoanine, haemanthamine, galanthine, incartine, O-methylpseudolycorine, hippeastrine,...
|
|
|
Natural toxins in food and their effect on human health
Houdková, Kristine ; Bušová, Milena (advisor) ; Schlenker, Anna (referee)
This bachelor thesis deals with the occurrence of natural toxic substances in food and describes their effect on human health. It focuses on toxic substances that are a natural part of plants, animals, and also on natural contaminants. This work is divided into theoretical and practical part. The aim of this work is to provide information and raise awareness about these substances, because they are an integral part of most foods. The purpose of the practical part is find out the level of public awareness of toxins in food and discover the frequency of mycotoxins appearences in food from the Rapid Alert System for Food and Feed (RASFF), which operates within the European Union. Mold toxins are a major worldwide problem, both in terms of public health and global economic. The research part of the work was carried out using a questionnaire survey through social networks. The general public seems to have a basic awareness of food safety and toxins substances in food. The bachelor thesis can serve as an informative and educational material for the public. Key words natural toxins - toxic substances - mycotoxins - alkaloids - poison
|
|
|
Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I
Wisura, Matěj ; Cahlíková, Lucie (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Matěj Wisura Supervisor: prof. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I The Amaryllidaceae family is considered to be very important source of biologicaly active natural compounds, alkaloids. These compounds are intensively studied because of their antiviral, antifungal, antiparasitic, antioxidative and antiinflammatory properties and especially for their ability to inhibit cholinesterases. This source is still not entirely depleted, which is proved by recent isolation of utterly new structural type of Amaryllidaceae alkaloids, carltonines, isolated form Narcissus pseudonarcissus cv. Carlton. Carltonines have shown promissing inhibitory activity of BuChE. Isolation of carltonines has become an inspiration for synthesis of highly selective BuChE inhibitors based on norbelladine structural type. This diploma thesis proceeds from pilot series of 20 compounds. During this study, another 21 compounds were prepared, expanding the portfolio and knowledge of structure-activity relationships within selective BuChE inhibitors group. Generated compounds were identified using NMR and ESI-HRMS....
|
|
|
Secondary metabolites of familly Apocynaceae as a souce of cytotoxic substances
Měšťanová, Kristýna ; Šafratová, Marcela (advisor) ; Hradiská Breiterová, Kateřina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Student: Kristýna Měšťanová Thesis supervisor: PharmDr. Marcela Šafratová, Ph.D. Thesis title: Secondary metabolites of the Apocynaceae family as a source of cytotoxically active substances The diploma thesis is focused on elaborating a comprehensive overview of secondary metabolites of the Apocynaceae family with a focus on their application in practice and the importance of Vinca alkaloids in the treatment of Hodgkin's and non- Hodgkin's disease. First, the major representatives of the Apocynaceae family, their constituents and mechanisms of action are mentioned. The uses and the desired and side effects are described and the effects of cardenolides are also stated. The work also deals with Hodgkin's and non-Hodgkin's disease, their incidence, symptomatology and classification of these diseases. Risk factors, including biological and genetic characteristics, are listed. Furthermore, the topic of staging and the treatment of these diseases according to the individual stages of the disease and differences in therapy of specific groups of patients are elaborated. The individual types of lymphomas, their diagnosis and subsequent treatment, including side effects, are described in detail. The...
|
guest ::
