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Secondary metabolites in fungal pathogenesis
Veselý, Martin ; Čmoková, Adéla (advisor) ; Machová, Lenka (referee)
The ability of fungal pathogens to induce infection and later survive in its host is dependent on virulence factors. Often these factors are based on primary metabolites (hydrophobins, proteases, phospholipases, catalases etc.). Nonetheless many pathogen produced secondary metabolites are also involved in the infection process. Their true role during infection used to be rather undervalued. First part of this bachelor degree thesis aims to describe host-pathogen relation and afterwards introduce reader with some basic, commonly accepted virulence factors of fungi. In the second part of this thesis known roles of secondary metabolites are described in each stages of progressing infection. In the first stage a pathogen needs to create a suitable habitat on host tissues to ensure growth. This is in part done by antimicrobial substances (...). In later stages pathogen prevents phagocytosis of its spores by host (melanins). Successful infection is often accompanied with host tissue damage that is induced by production of cytotoxic substances (xanthomegnin, riboflavin) and immunoregulation of host immune system (gliotoxin, pseurotin). Last but not least there are virulence factors that ensure prolonged survival in host (siderophores). Fungal pathogens of poikiloterm animals are mostly not primary...
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Natural compounds potentially influencing neurodegenerative diseases
Mňuková, Daniela ; Opletal, Lubomír (advisor) ; Suchánková, Daniela (referee)
Mňuková D.: Natural compounds potentially influencing neurodegenerative diseases. Diploma thesis, Charles University in Prag, Faculty of Pharmacy in Hradec Králové, Department os Pharmacognosy and Pharmaceutical botany, Hradec Králové 2022, 88 s. This research diploma thesis draws mainly from foreign professional literature. It provides an overview of important natural substances that potentially influence neurodegenerative diseases. The first part describes the moct common neurodegenerative diseases, their characteristics, epidemiology, pathogenesis and clinical picture. These diseases include Alzheimer's disease, Parkinson's disease, Lewy body dementia, multisystem atrophy, Pick's disease and other tauopathies, Huntington's disease, spinocerebellar ataxia and amyotrophic latelar sclerosis. The second part of diploma thesis presents natural substances that have been studied in preclinical and clinical studies in the last two decades for their potential to positively affect neurodegenerative diseases. The last part discusses the contribution of these natural substances fot therapy and prevention of neurodegenerative diseases. Keywords: neurodegenerative diseases, natural compounds, Alzheimer's disease, bioactive compounds
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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...
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Secondary metabolites and antimicrobial effects of neotropical members of the genus Hermatomyces
Ježková, Tereza ; Koukol, Ondřej (advisor) ; Žabka, Martin (referee)
Species of the genus Hermatomyces (Pleosporales) saprotrophs on wood and litter in the tropics. Since the secondary metabolites of this genus have not been investigated so far, this thesis focuses on them. In this thesis, the antifungal properties of the genus Hermatomyces were verified by pairing experiments on agar plates and by testing the minimum inhibitory concentrations of extracts obtained from fungal biomass. The extract of one selected strain, H. reticulatus CCF 5893, was separated by preparative HPLC. The selected biologically active fractions were purified and the chemical structure of the separated compounds was determined by nuclear magnetic resonance analysis and X-ray crystallography. Two compounds were found in this species: palmarumycins C2 and C12, which have antifungal properties. Furthermore, a total of 25 Hermatomyces strains were compared in terms of secondary metabolite production (by testing their minimum inhibitory concentrations and comparing HRMS data). Unique compounds were produced by H. megasporus, which also showed the highest antimicrobial activity of all species and is therefore the most suitable species for further study of antimicrobial compounds of this genus.
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Functions of secondary metabolites of lichens
Zvěřinová, Gabriela ; Svoboda, David (advisor) ; Bouda, František (referee)
This bachelor thesis is a review of available literature about lichen secondary metabolites and their functions. Lichens produce a great variety of these compounds; most of them are unique to the lichen symbiosis and are not found in higher plants. Besides the role of these compounds in chemotaxonomy and systematics, lichen secondary metabolites exhibit various biological functions and can affect biotic and abiotic interactions of lichens with their environment. Well-known and often described functions of lichen substances include especially antimicrobial, antiherbivory and antioxidant activity, allelopathy, metal homeostasis and photoprotection. This thesis is focused on these functions and summarizes current knowledge in this area. Key words: lichen, secondary metabolites, allelopathy, antimicrobial activity, herbivory, antioxidant activity, photoprotection, metal homeostasis, pollution tolerance, literary review
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Isolation of alkaloids of the species Magnolia soulangeana Soul.-Bod. and study of their biological activity
Baková, Izabela ; Hošťálková, Anna (advisor) ; Opletal, Lubomír (referee)
Baková I.: Isolation of alkaloids of the species Magnolia soulangeana Soul.-Bod. and study of their biological activity. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové, 2017. Key words: Magnolia solulangeana, secondary metabolites, alkaloids, biological activity. Secondary metabolites of plants are responsible for various biological activities. Alkaloids were described as a potentially suitable for Alzheimer's disease therapy (AD) through their inhibition activities against cholinesterases. Nowadays, these substances are important medicine for AD, therefore a screening of herbal drugs is still a current topic. An alkaloid extract of Magnolia × soulangeana flowers was tested in a preliminary testing on anticholinesterase activity. Because of the promising results, it was chosen for an isolation and identification possible effective alkaloids. The extract was separated by a column chromatography using aluminium oxide and a step gradient elution. Alkaloids were isolated by a repeated preparative thin-layer chromatography. Individual alkaloids were identified by a structural analysis (NMR, MS) and then their optical activity was measured. Substances were tested for an inhibition activity against human...
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Liquid Chromatography Methods for Analysis of Actinomycete Secondary Metabolites - Potential Antibiotics
Kameník, Zdeněk ; Nesměrák, Karel (advisor) ; Cvačka, Josef (referee) ; Bosáková, Zuzana (referee)
(EN) This dissertation thesis contains scientific results achieved in the field of analytical chemistry, particularly liquid chromatography. The major part of the results has been published in prestigious international journals in five papers. In addition to that, relevant yet unpublished results have been included as well. In general terms, the work presented here contributed to the concerted efforts to tackle the current lack of novel antibiotics. Specifically, high-performance liquid chromatography (HPLC) and ultra high-performance liquid chromatography (UHPLC) techniques coupled to a variety of detection systems have been employed for analysis of antibiotics and actinomycete secondary metabolites. The first thematic part describes the development of liquid chromatography methods for analysis of lincomycin precursors, lincomycin precursor analogues, and lincomycin derivatives. The methods have been applied to study lincomycin biosynthetic pathway and obtain improved lincomycin derivatives by mutasynthesis. The second thematic part aims at investigating alternative approaches for analysis of antibiotics. Firstly, the core-shell particle and the sub-2 μm particle chromatographic columns were compared. The core-shell particle columns compatible with HPLC proved to be a convenient alternative to the...
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Lessons from nature - preparation of hybrid bioactive compounds
Vobruba, Šimon ; Janata, Jiří (advisor) ; Zikánová, Blanka (referee)
Secondary metabolites are biologically active compounds produced mainly by microorganisms. They are not essential for survival of producing strains, however, they significantly affect their physiology and ecology. They are frequently used in pharmacology, biology and chemistry. The present work describes the current state of knowledge concerning origin and evolution of secondary metabolites. The secondary metabolites biosynthetic genes are usually organised in clusters. The basic mechanisms of secondary metabolite gene clusters modification are gene mutations or intragenic rearrangements. These mechanisms are typically involved in natural evolution of gene clusters coding for secondary metabolites with modular type of biosynthesis. The subclusters of different origin can also fuse to form a new hybrid compound biosynthetic gene cluster. Similar evolutionary event probably occurred also in case of biosynthesis of two model groups of natural compounds - lincosamides and pyrrolobenzodiazepines. Analogous approaches are used in genetic engineering to construct producers of new more efficient bioactive compounds. Examples of such genetic modifications of gene clusters involved in the biosynthesis of compounds from nonribosomal peptides, polyketides and lincosamides groups are described. Possible future...
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The effect of mycorrhiza on production of plant secondary metabolites
Pikorová, Markéta ; Albrechtová, Jana (advisor) ; Rydlová, Jana (referee)
Mycorhizal symbiosis, mutualistic relationship between symbiotic fungus and plant roots, is ranked among important interspecies interactions. It is indicated that about 90% terrestrial vascular plants live in this symbiosis. Arbuscular mycorrhiza (AM) is the most often occurring type of mycorrhiza and simultaneously the most often occurring type of symbiosis of higher plants. Approximately 80% of all of plant species form this symbiosis. By symbiotic coexistence with fungus plant often gains benefits as for example higher tolerance against stress factors, resistance against pathogens or improvement of nutrient uptake. In recent years in series of works is detected that mycorrhiza positively influences production of plant secondary metabolites. This influence can display quantitativelyby increase of metabolite in plant and also qualitatively by change spectrum of substances produced. These substances can have importance in different spheres for human. Medicinal research regularly extends spectum of substances with bioactive effect which have origin just in the plant secondary metabolism. Target of this thesis is, by the form of literary retrieval, to create an overview of recent state of research regarding of influence of mycorhizal symbiosis on content of secondary metabolites in plants, especially...
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Fungal secondary metabollites with antiviral activity
Besedová, Alena ; Čmoková, Adéla (advisor) ; Kolařík, Miroslav (referee)
The past year 2020 has clearly shown how quickly some viral infections can reach pandemic proportions. Thus, there is still a need to discover new substances with antiviral activity. Such substances (eg. asteltoxin E, cytosporaquinone B) have been discovered in the past in several groups of fungi, however, their potential as a source of virostatic chemotherapeutics has not been much explored. The possible use of fungi as a source of substances with antiviral activity is also indicated by the use of some species (eg. Ganoderma linghzi, Lentinula edoles) in the alleviation or prevention of viral diseases in traditional medicine. In most cases, however, it was not possible to find substances responsible for this effect. Therefore, in my bachelor's thesis I will first analyse kinds of fungi traditionally used as treatment of viral infections in traditional medicine. I will also summarize the most important fungal substances for which antiviral activity has been demonstrated. The bachelor's thesis will provide a comprehensive overview of currently known secondary metabolites of fungi and their virostatic effects. The information summarized in the work may point to possible candidates in the fight against viral infections.
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