in English This thesis is a review of substances contained in medicinal plants, the side effects and complications that they provoke. The adverse drug reactions are directly related to the constituents contained in each plant. Information for this work was taken from sources published from 1965 until 2013, especially from The Essential Guide To Herbal Safety and from the databases webmd.com and ncbi.nlm.nih.gov. It is discussed how the use of natural medicinal drugs affect vital organs in the human organism and in which cases their consumption is contraindicated. Central nervous, cardiovascular, urinary, gastrointestinal, endocrine, haemopoietic, respiratory, urinary systems are affected and allergic reactions are possible to occur as complications. Hypericum perforatum is typical for causing gastrointestinal irritations and Chamaemelum nobile and Achillea millefolium are found to cause dermatic complications. Finally, Piper methysticum may induce extreme sedation, since it has anxiolytic and antiepileptic properties. Keywords: side effects, contraindications, medicinal plants, uses, constituents.

Charles Universtity Pharmaceutical Faculty in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Jitka Karásková Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Natural compounds isolated from plants at the Faculty of Pharmacy in Hradec Králové as potential inhibitors of aldo-ketoreductase 1A1 (AKR1A1) Aldo-keto reductase 1A1 is an enzyme belonging to the aldo-keto reductase superfamily. It is a monomeric, cytosolic enzyme that is able to reduce carbonyl groups within a wide range of substrates. The enzyme is expressed in almost every tissue in the body, most represented in hepatocytes, renal cells and salivary glands, where it contributes to the reduction of endogenous substrates and the first phase of biotransformation of xenobiotics. AKR1A1 catalyzes NADPH-dependent reduction of aldehydes and ketones to their corresponding primary and secondary alcohols. Enzyme substrates include, for example, mevalonate; anthracycline antibiotics doxorubicin or daunorubicin; some pro-carcinogens that are activated by the reaction into carcinogens, such as: trans- dihydrodiol metabolites of polycyclic aromatic hydrocarbons. Generally, it is involved in the metabolism of lipids and carbohydrates that contain an aldehyde function. The increased expression and activity of AKR1A1 has been...

Submitted in fulfillment of the requirements of the Degree of Doctor of Technology: Chemistry,Durban University of Technology, 2014. / Aromatic heterocycles are highly important structural units found in a large number of biologically active natural compounds, pharmaceuticals and catalytic compounds. They have a crucial role in organic syntheses, which results in the generation of high value products. Among heterocycles, those containing nitrogen are the most indispensable structural motifs and are widely used against dreaded diseases such as Malaria, TB, HIV/AIDS and Cancer. The inclusion of highly electronegative atoms such as fluorine in these organic molecules render them very reactive towards proteins. Furthermore these molecules exhibit strong interactions with surfaces of quantum range particles of elemental gold. Various approaches for the synthesis of novel gold nanoparticles linked to potent bioactive molecules are documented and their application as drug delivery systems are of immense value to human health. Also many chemical and physical methods are available for the synthesis of gold, silver and palladium nanoparticles however these methods are usually laborious and produce toxic by-products. The green approach is to use plant extracts to synthesise various size and shape nanoparticles which could be used in biological and catalytic systems. A simple one-pot two component and three component reaction using formyl quinoline, 2-aminothiophenol, thiosemicarbazone and trifluoromethylbenzaldehyde as a reactant to synthesise quinoline, pyridine and pyran based bioactive small molecules; these products are a quinoline type bearing a benzothiazole moiety, quinoline thio semicarbazone ligand, fluorine substituted dihydro pyridine, fluorine substituted dihydropyran and fluorine substituted pyridine derivatives. In total, fifteen compounds were synthesized eleven of which were novel; all compounds were characterized by spectroscopic techniques. In vitro anti-bacterial activities of the synthesized compounds were investigated against a representative panel of pathogenic strains. Compounds 6, 7, 8, 11 and 13 exhibited excellent anti-bacterial activity compared with first line drugs. Potent p53–MDM2 interaction inhibitors 2-thio-1,2-dihydroquinoline-3-carbaldehyde thiosemicarbazone and fluorine substituted new pyridine scaffold were successfully identified by structure-based design. An efficient one-pot four component route to the synthesis of trifluorinated pyrrolophenanthroline and fluoroquinoline pyrrolophenanthrolines was designed. In this reaction 1-butyl-2,3-dimethylimidazolium tetrafluoroborate ionic liquid (DMTIL) was used as a reaction medium; no catalyst was required. The structure of the pyrrolophenanthrolines was deduced by IR and NMR analysis. These compounds were studied with Bovine Serum Albumin (BSA) through molecular docking. Hydrophopic, electrostatic and hydrogen bonding interaction played a crucial role in the binding to sub domain of BSA. Interaction studies of DMTIL with BSA by emission, absorption, synchronous fluorescence, circular dichroism (CD) and three dimensional emission (3D) spectroscopic techniques were under taken. The results from emission titration experiments revealed the existence of a strong interaction between BSA and DMTIL ionic liquid. It showed that compounds with lesser number of hydrogen bonds are found to be more active which is attributed to hydrophobic interaction and electrostatic interaction which also played a vital role in DMTIL binding to sub domain IB of BSA. A novel copper-loaded boron nitride nanosheet (Cu/BN) catalyst was prepared and fully characterized. It was used as an efficient and chemoselective catalysts for the synthesis of α-aminophosphonates by the Kabachnik-Fields reaction; twenty one α-aminophosphonates were synthesised. The enhanced catalytic activity and product yield was attributed to the increase of surface acidity. Overall, this methodology offered competitive advantages such as recyclability of the catalyst without further purification or without using additives or cofactors, low catalyst loading, broad substrate applicability and high yields. The application of this new nanocatalyst in organic synthesis will provide a novel pathway for the synthesis of pharmaceutically important compounds. Gold nanoparticle surfaces were modified with self-assembled monolayers of important thiol and disulfide bioactive molecules since considerable interest is due to their potential application as anti-cancer agents. Herein, a carbazole was conjugated to lipoic acid by using an amide coupling catalyst HBTU and DIEA reaction. The structure of the carbazole thio octanic acid (CTN) was identified by IR and NMR. CTN was attached to the gold nanoparticles surface and the capping behaviour was characterized by UV-vis spectroscopy, TEM, DLS and FTIR. The cytotoxicity of CTNAuNPs on A549 cell lines was determined using the MTT assay. The results suggest CTN and CTNAuNPs possess anti-proliferative properties in the cancerous A549 cells. Furthermore a dual thiol ligand was synthesized by using equimolar 4-aminothiophenol (4-ATP) and amino oxadiazole thiol (AXT). This dual ligand was attached to the gold nanoparticles surface (DTAu) and the capping behaviour was characterized by UV-vis spectroscopy, TEM, DLS and FTIR. The cytotoxicity of DTAu on A549 cell lines was determined using the MTT assay. The results suggest dual ligands (4-ATP, AXT) and DTAu possess anti-proliferative properties in the cancerous A549 cells. South African indigenous plants and agroforestry waste were also used in the synthesis of silver, gold and palladium nanoparticles (NPs). Green protocols such as the use of environmentally benign solvents and non-hazardous reagents were an added advantage to physical and chemical means. Furthermore these reactions were rapid and the size and shape of the NPs could be manipulated by choosing the correct medium. The formulation of natural medicinal compounds capped onto NPs was assessed for their anti-cancer activity, in A549 lung cancer line, and catalytic reduction of dyes and nitrobenzene derivatives were studied. These NPs displayed: Significant cytotoxicity to lung cancer cells with minimal effect on normal healthy cells. Outstanding catalytic reduction of pharmaceutical and textile waste effluents such as dyes and nitro aromatic compounds. In addition, palladium nanoparticles containing capped Moringa olifera compounds were used effectively in the Suzuki coupling reaction of iodobenzene and phenylboronic acid. The reaction was rapid and was conducted in an aqueous medium.

Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Andrea Homerová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Interaction of natural substances with human aldo-keto reductase 7A2 and other important carbonyl reducing enzymes Reduction of carbonyl group is one of the phase I metabolism reactions, which is responsible for production of more polar metabolites, enables conjugation in process of biotransformation, excretion of the molecule and it also causes decrease in reactivity and biological activity of the molecule. Endogenous as well as exogenous compounds undergo this reaction and carbonyl reducing enzymes are the ones which possess this reducing activity. Based on the structure, we can divide the enzymes into several groups: short-chain dehydrogenases/reductases, medium-chain dehydrogenases/reductases, aldo-keto reductases and quinone reductases. Inhibition of carbonyl reducing enzymes appears to be a promising aim of research. It is important to take into consideration that by inhibiting carbonyl reducing enzymes it is possible to reduce production of less active, but more toxic metabolites, for example in anthracycline chemoteraputics daunorubicin and doxorubicin and that can lead to change in therapy of cancer. This study...

Hradecká M.: Natural compounds applicable for the treatment of metabolic syndrome, Diploma thesis 2018/2019, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, pp. 60. Occurence of metabolic syndrome is increasing worldwide in children and adults. The use of natural compounds is one of possibilities in the prevention and treatment of metabolic syndrome. These compounds may act complexly or affect individual risk factors associated with metabolic syndrome. Selected plants with these effects are incorporated into my diploma thesis (for example Allium sativum, Crataegus laevigata, Hibiscus sabdariffa, Persea americana, Rosmarinus officinalis, Silybum marianum and Vaccinium myrtillus). The alga Undaria pinnatifida and fungus Pleurotus sajor-caju are also mentioned. It is necessary to carry out other clinical studies, where the positive effect of mentioned constituents will be confirmed, which could be added to the list of phytopharmaceuticals used to prevent, slow down or treat the metabolic syndrome in the future. Keywords: natural compounds, metabolic syndrome

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Bc. Alžběta Vopelková Supervisor: doc. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Using of techniques of mass spectrometry in the analysis of natural compounds This diploma thesis deals with the topic " Using of techniques of mass spectrometry in the analysis of natural compounds ". The aim of the work was to create a research work and describe the profile of alkaloids in individual genera of the family Amaryllidaceae. The introduction to the theoretical part summarizes the analyzes gas chromatography (GC). Alkaloids have been classified according to their heterocyclic parts and the family Amaryllidaceae has been described. The work was based on professional texts by Czech and foreign authors. Used sources focused on the analysis of alkaloids in bulbs, or in the aboveground parts of plants in this family, using gas chromatography with mass detection (GC-MS). Key words: mass spectometry, analysis, natural compounds

The medical mushroom Ganoderma lucidum has long been used in traditional Chinese medicine and shown effective in the treatment of many diseases including cancer. Here we studied the cytotoxic effects of two natural compounds purified from Ganoderma lucidum, ergosterol peroxide and ganodermanondiol. We found that these two compounds exhibited cytotoxicity not only against fast proliferating cells, but on quiescent, slow-cycling cells. Using a fibroblast cell-quiescence model, we found that the cytotoxicity on quiescent cells was due to induced apoptosis, and was associated with a shallower quiescent state in compound-treated cells, resultant from the increased basal activity of an Rb-E2F bistable switch that controls quiescence exit. Accordingly, we showed that quiescent breast cancer cells (MCF7), compared to its non-transformed counterpart (MCF10A), were preferentially killed by ergosterol peroxide and ganodermanondiol treatment presumably due to their already less stable quiescent state. The cytotoxic effect of natural Ganoderma lucidum compounds against quiescent cells, preferentially on quiescent cancer cells vs. non-cancer cells, may help future antitumor development against the slow-cycling cancer cell subpopulations including cancer stem and progenitor cells.

Development of new asymmetric processes is one of the objectives of catalysis in organic chemistry. These processes can provide access to chiral building blocks applicable in syntheses of various natural substances that can be used for medical purposes. One such process is the preparation of chiral homoallyl alcohols, which have been used for syntheses of variety of biologically active compounds. In view of the aforementioned, suitably substituted homoallyl alcohols could be used as intermediates in syntheses of koibacins A-D, which have a number of interesting biological properties. Natural koibacins A-D are metabolites isolated from the marine cyanobacterium Oscillatoria sp. that exhibits selective antileishmanial activity and potent antïinflammantory properties. Our synthetic plan is focused on an approach through the allylation of aldehydes, esterification, ring closing metathesis and finally cross metathesis with different lipophilic fragments. Key words: enantioselective allylation, asymmetric synthesis, natural compounds, coibacins.

O comportamento eletroquímico do aço carbono em soluções aquosas contendo KNO3 0,10 mol L-1 e soluções etanólicas contendo cloreto de tetraetilamônio 0,10 mol L-1 foi estudado na ausência e na presença de diferentes concentrações (0,50 mM a 50,0 mM) de acetato de linalila, mentol, limoneno e pulegona. Técnicas eletroquímicas como a potenciometria, varredura potenciodinâmica, cronoamperometria, curvas de Tafel e espectroscopia de impedância eletroquímica foram utilizadas a fim de compreender a interação entre os compostos orgânicos e a superfície do eletrodo. Medidas de perda de massa também foram realizadas, bem como a comprovação visual dos resultados mediante registros fotográficos. O acetato de linalila adsorve na superfície do aço carbono mesmo na presença de grande quantidade de água ou etanol. A energia livre de adsorção de Gibbs para este processo é de -26,0 kJ mol-1 em soluções aquosas e -26,7 kJ mol-1 em soluções etanólicas. Para o mentol, a energia livre de adsorção de Gibbs calculada foi de -26,7 kJ mol-1 em soluções aquosas e -24,2 kJ mol-1 em soluções etanólicas. Para o limoneno, esses valores foram -24,2 kJ mol-1 em meio aquoso e -26,0 kJ mol-1 em meio etanólico, e para a pulegona os valores foram de -25,7 kJ mol-1 e -24,6 kJ mol-1, em meio aquoso e etanólico, respectivamente. Foi detectado que as espécies adsorvidas na superfície do metal diminuíram os valores das densidades de corrente anódicas, bem como a perda de massa do metal. Esses efeitos permitem-nos classificar esses compostos orgânicos como inibidores naturais de corrosão para o aço carbono em soluções aquosas e etanólicas. / The electrochemical behavior of low carbon steel in aqueous solutions containing KNO3 0.10 mol L-1 and ethanolic solutions containing tetraethylammonium chloride 0.10 mol L-1 was studied in the absence and presence of different concentrations (0.50 mM to 50.0 mM) of linalyl acetate, menthol, limonene and pulegone. Electrochemical techniques such as potentiometry, cyclic voltammetry, chronoamperometry, Tafel curves and electrochemical impedance spectroscopy were used to understand the interaction between the organic compound and the electrode surface. Weight loss measurements were also performed, as well as visual confirmation of the results by photographic records. Linalyl acetate adsorbed on low carbon steel surface even in the presence of a large amount of water or ethanol. The Gibbs free energy of adsorption for this process was -26.0 kJ mol-1 in aqueous solutions and -26.7 kJ mol-1 for ethanol solutions. For menthol, the Gibbs free energy of adsorption was calculated -26.7 kJ mol-1 in aqueous solutions and -24.2 kJ mol-1 for ethanol solutions. For limonene, these values were -24.2 kJ mol-1 in aqueous medium and -26.0 kJ mol-1 in ethanolic medium, and for pulegone the values were - 25.7 kJ mol-1 and -24.6 kJ mol-1 in aqueous and ethanolic medium, respectively. It was detected that the species adsorbed on the metal surface decreased the amounts of anodic current densities and the metal mass loss. These effects allow us to classify the organic compounds investigated as natural corrosion inhibitors for low carbon steel in aqueous and ethanolic solutions.

O comportamento eletroquímico do aço carbono em soluções aquosas contendo KNO3 0,10 mol L-1 e soluções etanólicas contendo cloreto de tetraetilamônio 0,10 mol L-1 foi estudado na ausência e na presença de diferentes concentrações (0,50 mM a 50,0 mM) de acetato de linalila, mentol, limoneno e pulegona. Técnicas eletroquímicas como a potenciometria, varredura potenciodinâmica, cronoamperometria, curvas de Tafel e espectroscopia de impedância eletroquímica foram utilizadas a fim de compreender a interação entre os compostos orgânicos e a superfície do eletrodo. Medidas de perda de massa também foram realizadas, bem como a comprovação visual dos resultados mediante registros fotográficos. O acetato de linalila adsorve na superfície do aço carbono mesmo na presença de grande quantidade de água ou etanol. A energia livre de adsorção de Gibbs para este processo é de -26,0 kJ mol-1 em soluções aquosas e -26,7 kJ mol-1 em soluções etanólicas. Para o mentol, a energia livre de adsorção de Gibbs calculada foi de -26,7 kJ mol-1 em soluções aquosas e -24,2 kJ mol-1 em soluções etanólicas. Para o limoneno, esses valores foram -24,2 kJ mol-1 em meio aquoso e -26,0 kJ mol-1 em meio etanólico, e para a pulegona os valores foram de -25,7 kJ mol-1 e -24,6 kJ mol-1, em meio aquoso e etanólico, respectivamente. Foi detectado que as espécies adsorvidas na superfície do metal diminuíram os valores das densidades de corrente anódicas, bem como a perda de massa do metal. Esses efeitos permitem-nos classificar esses compostos orgânicos como inibidores naturais de corrosão para o aço carbono em soluções aquosas e etanólicas. / The electrochemical behavior of low carbon steel in aqueous solutions containing KNO3 0.10 mol L-1 and ethanolic solutions containing tetraethylammonium chloride 0.10 mol L-1 was studied in the absence and presence of different concentrations (0.50 mM to 50.0 mM) of linalyl acetate, menthol, limonene and pulegone. Electrochemical techniques such as potentiometry, cyclic voltammetry, chronoamperometry, Tafel curves and electrochemical impedance spectroscopy were used to understand the interaction between the organic compound and the electrode surface. Weight loss measurements were also performed, as well as visual confirmation of the results by photographic records. Linalyl acetate adsorbed on low carbon steel surface even in the presence of a large amount of water or ethanol. The Gibbs free energy of adsorption for this process was -26.0 kJ mol-1 in aqueous solutions and -26.7 kJ mol-1 for ethanol solutions. For menthol, the Gibbs free energy of adsorption was calculated -26.7 kJ mol-1 in aqueous solutions and -24.2 kJ mol-1 for ethanol solutions. For limonene, these values were -24.2 kJ mol-1 in aqueous medium and -26.0 kJ mol-1 in ethanolic medium, and for pulegone the values were - 25.7 kJ mol-1 and -24.6 kJ mol-1 in aqueous and ethanolic medium, respectively. It was detected that the species adsorbed on the metal surface decreased the amounts of anodic current densities and the metal mass loss. These effects allow us to classify the organic compounds investigated as natural corrosion inhibitors for low carbon steel in aqueous and ethanolic solutions.