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Novel phthalocyanine photosensitizers for photodynamic therapy of tumorous diseases
Zvolánková, Kateřina ; Macháček, Miloslav (advisor) ; Jirkovská, Anna (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kateřina Zvolánková Supervisor: Mgr. Miloslav Macháček Title of diploma thesis: Novel phthalocyanine photosensitizers for photodynamic therapy of tumorous diseases Oncological diseases are considered to be a serious global problem for many years. One of the most significant factors of their expansion in human population is an increasing life expectancy. Higher incidence of physical and chemical carcinogens and better diagnostic methods of malignant neoplasms are farther possible factors. According to World Health Organisation (WHO) almost 8 million people in the world die from oncological disease every year, whereas 1.7 million of them are Europeans. Malign tumours in Czech Republic, as well as in the world, are the second most frequent causes of death right after cardiovascular diseases, in both genders. Despite increasing incidence of malign tumours in the world, the mortality rate is decreasing. This decline is connected especially with higher quality of medical care together with availability of new diagnostic and therapeutic means. Thus the therapy of cancer is an important subject of biomedical research. Scientists have been trying to discover an effective and highly selective...
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Synthesis of tetrazole derivatives with high antimycobacterial activity and their initial in vitro toxicity assessment
Kavková, Věra ; Macháček, Miloslav (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Věra Kavková Supervisor: Mgr. Miloslav Macháček Consultant: PharmDr. Jaroslav Roh, Ph.D. Title od diploma thesis: Synthesis of tetrazole derivatives with high antimycobacterial activity and their initial in vitro toxicity assessment Tuberculosis is still one of the most dangerous and widespread infection diseases causing deaths of more than 1.5 million people worldwide each year. Tuberculosis is a specific disease with a complicated treatment and unique pathogenesis and disease progression. Mycobacterium tuberculosis complex strains represent the most common progenitor of tuberculosis. The disease itself is treatable nowadays and its diagnosis is very well established. On the other hand it is still causing fatal problems especially in immunosuppressant and HIV positive patients not only in developing countries. Another unmissable problem is also alarming increase of strains resistant to standardly used antituberculosis treatment. Hence in order to eradicate inception and spreading of the resistant strains the emphasis is on the development engaged in the research for new and more effective antituberculotics which would make treatment of this disease easier and faster especially in...
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In vitro study of newly synthesized potential cardioprotective drugs
Liptáková, Lucie ; Hašková, Pavlína (advisor) ; Macháček, Miloslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Liptáková Supervisor: RNDr. Pavlína Hašková, Ph.D. Title of master thesis: In vitro study of newly synthesized potential cardioprotective drugs Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are in an organism generated under normal or pathological conditions. There are antioxidant mechanisms, which protects the organism from their harmful effect. In case of imbalance between ROS/RNS production and antioxidant mechanisms, an oxidative stress is initiated. The oxidative stress is involved in the pathogenesis of many diseases, including cardiovascular desease. In consequence of higher presence of mitochondria and lower presence of antioxidants cardiomyocytes are more sensitive to the oxidative stress. Iron, by catalysing radical's reactions, significantly participates on formation and development of oxidative stress. Elimination of the free iron by iron chelators is one option how to prevent or moderate oxidative stress. The aim of this master theses was to study cardioprotective effect in presence of H2O2 and own toxicity of newly synthetized aroylhydrazone iron chelators (H21, H22, H23, H24, H25 and H26) on rat embryotic cardiomyoblasts H9c2. Protective and toxic...
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Contribution of Next Generation Sequencing for Laboratory Diagnostics
Votýpka, Pavel ; Beránek, Martin (advisor) ; Macháček, Miloslav (referee)
5 ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Pavel Votýpka Supervisor: Doc. PharmDr. Martin Beránek, Ph.D. Consultant: Mgr. Nikola Ptáková Title of diploma thesis: Contribution of Next Generation Sequencing for Laboratory Diagnostics The endeavor to sequence the whole human genome lead not only to the knowledge acquisition regarding the human genetic information but as well to the development of new sequencing methods and technologies. In order to keep up with progress in genetic field in many clinical and research laboratories the new massive parallel sequencing equipment is being utilized. On the market are currently established four leading platforms - Illumina, Solid, Ion Torrent and 454 Life Technologies. The process of sequencing analysis can be summarized into three main steps - the sequencing library preparation, sequencing itself, variant calling and data analysis. Each part of the sequencing analysis exhibits certain specifics, we need to count with and as well its pitfalls, we need to avoid or to minimalize their impact on the analysis final result. Recently new methods termed sequencing of the 3rd generation are being developed, enabling sequence of a single DNA molecule to be determined without previous...
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Study of cytoprotective properties of novel oxidative stress-activated aroylhydrazone pro-chelators of iron
Macháček, Miloslav ; Šimůnek, Tomáš (advisor) ; Lenčová, Olga (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Miloslav Macháček Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Study of cytoprotective properties of novel oxidative stress-activated aroylhydrazone prochelators of iron Oxidative stress plays an important role in many disorders including cardiovascular diseases. Fenton reaction catalysed by intracellular redox-active iron is an important source of highly reactive and toxic hydroxyl radicals. Hence, shielding of free iron ions seems to be an advantageous strategy for prevention of further propagation of oxidative stress and myocardial damage. Results from our laboratory as well as other groups have shown promising cardioprotective effect in vitro as well as in vivo experiments. On the other hand, excessive depletion of iron may result in toxicity to the cells. The aim of this project was therefore to examine new iron prochelators, which chelating activity develops only after activation by reactive oxygen species. Boronyl ester of salicylaldehyde isonicotinoyl hydrazone (BSIH) and its derivate BSIH-PD were examined in vitro for their potential protective properties against toxic reactive oxygen species (ROS). Furthermore, own toxicities of studied compounds...
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Study of the novel phtalocyanines for the vascular-targeted photodynamic therapy of tumors
Brázdová, Petra ; Macháček, Miloslav (advisor) ; Šimůnek, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Petra Brázdová Supervisor: Mgr. Miloslav Macháček Title of diploma thesis: Study of the novel phthalocyanines for the vascular-targeted photodynamic therapy of tumors Cancer is one of the leading causes of death in developed countries, therefore a big effort is devoted on research of novel anticancer drugs. Photodynamic therapy (PDT) is currently a well-established method in this area, but targeting its effect on tumor vasculature has not been considered until recently. In comparison with PDT, vascular-targeted photodynamic therapy (VTP) takes the advantage of a much shorter interval between administration of the photosensitizer (PS) and irradiation (drug-light interval) and thus turning the effect of cytotoxic agents to tumor vasculature. It is intended to disrupt the oxygen and nutrients supply to malignant cells and thus cause their damage and death. Aim of this work is to evaluate the efficacy of newly synthesized PSs from the group of phthalocyanines and azaphthalocyanines using the VTP protocol under in vitro conditions. The PSs used in this study have been investigated recently with classical PDT protocol, in which they have demonstrated very promising activity against tumor cells...
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In vitro evaluation of photodynamic activity of tetrapyridoporphyrazine derivatives for treatment of solid tumours.
Jedličková, Adéla ; Macháček, Miloslav (advisor) ; Šimůnek, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradci Králové Department of Biochemical Sciences Candidate: Bc. Adéla Jedličková Supervisor: Mgr. Miloslav Macháček Title of diploma thesis: In vitro evaluation of photodynamic activity of tetrapyridoporphyrazine derivatives for treatment of solid tumors Nowadays, cancerous diseases belongs among the main causes of death, incidence continues to rise. Therefore research in the area of tumor treatment significantly focuses on the development of new potential anticancer drugs and therapeutical approaches. Photodynamic therapy (PDT) belongs to clinically approved therapeutic methods for the treatment of the malignant and nonmalignant diseases. PDT is composed of three main components - photosensitiser (PS), light and oxygen, all of them are non-toxic on their own. However, their interaction leads to a generation of highly reactive molecules. This method is based on absorption of light with appropriate wavelenght by PS and subsequent energy transfer from photon to surrounding molecules, especially to oxygen. This transfer leads to a generation of cytotoxic reactive oxygen species (ROS) of which singlet oxygen plays a main role. ROS subsequently causes a damage of surrounding cell structures, which leads to irreversible damage of cell functions and...
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