Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Alžbeta Tomanová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Effect of selected tyrosine kinase inhibitors on the activity of human carbonyl reducing enzymes Key words: tyrosin kinases, screening, carbonyl, daunorubicin, inhibition Tyrosine kinases are a subclass of protein kinases, catalysing the transfer of ATP phosphate residue to a protein, thereby playing an important role in cellular signaling. Abnormal tyrosine kinase activity is present in various malignancies. In certain cases, inhibition of their function can prevent tumor cell proliferation and eventually induce apoptosis. At the same time, some tyrosine kinase inhibitors have demonstrated the ability to inhibit efflux transporters, which are often involved in the development of resistance to anticancer treatment. In this diploma thesis, the inhibitory effect of imatinib, nilotinib, dasatinib and acalabrutinib (tyrosine kinase inhibitors) has been studied on carbonyl reducing enzymes, whose overexpression by tumor cells may lead to resistance to chemotherapy. In particular, in the case of anthracyclines, the reduction of carbonyl group on C-13 results in not only lower cytotoxic activity, but also increased...

Trälim utgör en stor del av alla lim globalt och är avgörande för skapandet av träkompositmaterial, som många industrier och produkter är beroende av. Bland de vanligaste trälimmen använder flera formaldehyd som en väsentlig komponent i deras polymera struktur. Medan formaldehyd är ett allmänt använt, billigt och pålitligt material, är det också giftigt och har generellt ursprung från petroleumkällor. Ett ersättningsmaterial med di- eller polyaldehydisk funktionalitet av grönt ursprung är därför önskvärt för framtida trälimkemi. En potentiell lösning involverar att oxidera polysackarider såsom stärkelse och dextrin för att funktionalisera de upprepande glukosenheterna med aldehyder, ketoner och karboxylsyror. Här visas att Fenton-liknande förhållanden, med väteperoxid som oxidationsmedel och järn som katalysator, kan användas för att utföra reaktionen effektivt under atmosfäriska förhållanden, vilket producerar minimala biprodukter såsom vätgas, vatten och järnkomplex. Betydande funktionalisering observerades i en lågmolekylviktsfraktion som frigörs från polysackariden vid oxidation, en fraktion som traditionellt förloras under upparbetning via centrifugering. Detta arbete antyder att retention av denna lågmolekylviktsfraktion i produktblandningen kan förbättra framtida limegenskaper vid låg grad av oxidation i material med hög polymerisationsgrad, även om kvarhållande av depolymeriserade fraktioner från material med lägre polymeriseringsgrad, såsom dextrin, kanske inte ger de önskade polyaldehydiska produkterna i tillräckliga koncentrationer. Kvarhållandet av lågmolekylviktsfraktionen antyder också att stora mängder oxidationsmedel och katalysator bör undvikas, eftersom högre oxidationsgrad kan resultera i oönskade monofunktionella molekyler på grund av hög depolymerisation. / Wood adhesives comprise a large part of all adhesives globally and are essential in creation of wood composite materials, which many industries and products are entirely reliant on. Amongst the most common wood adhesives, several utilize formaldehyde as an essential component of their polymeric structure. While formaldehyde is a widely used, cheap and reliable material, it is also toxic, and generally derived from petroleum sources. A replacement with di- or poly-aldehydic functionality of green origin is therefore desirable for future wood adhesive chemistry. One potential solution involves oxidizing polysaccharides such as starch and dextrin, to functionalize the repeating glucose units with aldehydes, ketones, and carboxylic acids. Herein, it is demonstrated that Fenton-type conditions, using hydrogen peroxide as oxidant and iron as catalyst, can be used to perform the reaction efficiently in atmospheric conditions, producing minimal byproducts such as hydrogen gas, water, and iron complexes. Significant functionalization was observed in a small molecular weight fraction released from the polysaccharide upon oxidation, a fraction which is traditionally lost during workup via centrifugation. This work suggests that retention of this small molecular weight fraction in the product mixture may enhance future adhesive properties at low degrees of oxidation in materials with high degrees of polymerization, though retention of depolymerized fractions of lower chain length materials such as dextrin may not provide the targeted poly-aldehydic products in sufficient concentrations. The retention of the small molecular weight fraction also suggests that large amounts of oxidant and catalyst should be avoided, as higher degree of oxidation may result in undesired mono-functional molecules due to higher degrees depolymerization.

Title: Theoretical study of spin-orbit coupling on spectra and photophysics of rhenium complexes Author: RNDr. Radka Heydová Department: Physical and Macromolecular Chemistry Supervisor: Ing. Stanislav Záliš, CSc., JHI AS CR, v.v.i. Supervisor's e-mail address: stanislav.zalis@jh.inst-cas.cz Abstract: Relativistic effects, especially spin-orbit coupling (SOC), play an essential role in transition metal chemistry and SOC treatment is indispensable for a correct theoretical description. To demonstrate the importance of SOC, the energies and oscillator strengths of vertical transitions for a series of [ReX(CO)3(2,2'-bipyridine)] (X = Cl, Br, I) and [Re(imidazole)(CO)3(1,10-phenanthroline)]+ complexes were calculated in the spin-free (SF) and spin-orbit (SO) conceptual frameworks. Two different computational approaches were adopted: SO-MS-CASPT2 where SOC was added a posteriori using a configuration interaction model (SO-RASSI), and the approximate perturbative SO-TD-DFT method. Relativistic effects were included via the two-component Douglas-Kroll-Hess transformation and the zeroth-order regular approximation in the former and the latter technique, respectively. The SF (i.e. accounting only for the scalar relativistic effects) and SO results from both methods were compared with each other and to available...