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Targeted azole prodrugs with antifungal activity
Černá, Lucie ; Baszczyňski, Ondřej (advisor) ; Sedláček, Ondřej (referee)
Invasive fungal infections (IFIs), mostly caused by Aspergillus or Candida species, represent a severe global threat. IFIs are serious diseases of great concern especially in immunocompromised patiens, annually leading to more than 1.7 million deaths.1 Despite its seriousness, there is insufficient amount of available antifungal therapeutics. Current antifungal treatments rely mainly on azole drugs which often suffer from increased toxicity, low bioavailability and drug resistance, among others.2 Therefore, we aim to develop novel antifungals in the form of azole prodrugs which would selectively target specific fungal enzymes and would ideally avoid undesired off-target effects. Our designed prodrugs contain selected azoles, modified by the attachement of a self-immolative (SI) linker to a specific carbohydrate through a glycosidic bond. Such glycosidic bond should undergo cleavage by extracellular fungal glycosidases, resulting in release of the azole drug directly at the site of fungal infection. Keywords: azole, antifungal, prodrug, targeted delivery
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Analytical methods for hyaluronan
Černá, Lucie ; Mravec, Filip (referee) ; Pekař, Miloslav (advisor)
This thesis deals with of simple methods for determining the concentration of hyaluronan in aqueous solution and compares the performance of each selected methods such as UV -VIS spectroscopy, IR spectroscopy and the method of determination by alcian blue. These methods were chosen for their simplicity and low cost of the assay. As the most reliable of these three methods, seems to be the method of IR spectroscopy. Determination of the concentration of HA by this method is relatively accurate at concentrations above 0.4 % in deionized water. The method of UV-VIS spectroscopy is based on a linear calibration curve determination, but no characteristic peak was detected, which means that this determination could be influenced by other components of the aqueous solution. Weak ionic strength and molecular weight of HA does not affect the determination. In the method with alcian blue, the results were quite unsatisfactory and does not correspond with the literature. Therefore, this method is not applicable in this form for determining the concentration of HA. Another option for determining the concentration of the HA is ELISA method. These are commercially produced kits suitable for determining low concentrations in low volumes. Its price is higher than the above- mentioned methods.
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Methods for determination of hyaluronan
Černá, Lucie ; Venerová, Tereza (referee) ; Pekař, Miloslav (advisor)
This thesis deals with a summary of individual method for determining of hyaluronan concentration, especially in aqueous solutions. Selected methods were compared to their functionality in university workplace. Any functional methods may be used for many purposes in university workplace in research of materials based on hyaluronan. It has been studied usability to assess residual content of hyaluronan in supernatant of gel formed from hyaluronan and surfuctant, in this thesis. We choosed sptectrophotometric methods, especially with UV spectroscopy and IR spectroscopy. Two precipitation methods using alcian blue were also tested. As the most reliable, the least demanding and specific method seems to be the method using IR spectroscopy, thanks to it we are able to determine the concentration of HA from 0.01 %. With this method, it has been found, that if there will be located some amount of HA in supernatant, it will be below the detection limit of assay. The remanining methods were modified to help determine the concentrations of HA, but works only in aqueous solutions. A possible variation for determination of very low concentrations of HA may be the method using ELISA kits. However their cost is higher than the above-mentioned methods.
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Derivatives of N-acetylglucosamine-1-phosphate as potential inhibitors of UDP-GlcNAc pyrophosphorylase
Černá, Lucie ; Baszczyňski, Ondřej (advisor) ; Veselý, Jan (referee)
This bachelor thesis deals with the preparation of phosphonate derivatives of N-acetyl- ᴅ-glucosamine-1-phosphate (GlcNAc-1-P), the substrate for UDP-GlcNAc pyrophospho- rylase (UAP1) enzyme, which is responsible for the chitin synthesis in fungal cell walls. Structural analogs of GlcNAc-1-P could potentially inhibit UAP1 and; therefore, their synthesis may enable the development of new antifungal drugs. This work is mainly focused on the synthesis of diethyl (2-acetamido-1,2-dideoxy-β-ᴅ-glucopyranosyl)phosphonate which was selected as a key model compound. The goal was to find the most suitable synthetic route leading to the synthesis of phosphonate and phosphinate GlcNAc-1-P analogues. Two synthetic methods were studied: 1) Michael addition of H-phosphonates to 2-nitroglucals; and 2) nucleophilic substitution of activated GlcNAc substrates (trichloroacetimidate and bromide) by phosphorus nucleophiles. Keywords: GlcNAc-1-P, UDP-GlcNAc pyrophosphorylase, antifungal, inhibitor
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Comparison of legal regulation of patents in the Czech Republic and the People's Republic of China
Černá, Lucie ; Rozehnal, Aleš (advisor) ; Horáček, Tomáš (referee)
Comparison of legal regulation of patents in the Czech Republic and the People's Republic of China - Abstract This thesis compares legal system of patents in Czech Republic and People's Republic of China with the focus on Patent Laws and other legislation in respective countries. The aim of this paper is to present the approach that Czech and Chinese society adopted with respect to patent law, together with its' historical evolution in both compared countries. This historical insight into the evolution of patent legislation is aimed to help the reader to understand, why certain legislation is present in national patent laws, even though both countries are members of WTO and WIPO and parties to Paris Convention for the Protection of Industrial Property. Another goal of this thesis is to compare the national patent legislation of individual patent institutes, to highlight the differences of such patent institutes and map the influence that the international treaties and international organizations have on the national patent legislation of its' respective country. Finally, this thesis will attempt to briefly introduce the Chinese system of patent enforcement and its practical application when the patentee seeks patent enforcement with Chinese authorities. This diploma thesis is divided into four chapters. The...
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