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Synthesis of novel cardioprotectants and metabolites of potent anticancer drug - Bp4eT
Eisner, Tomáš ; Roh, Jaroslav (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy Hradec Králové Department of Organic and Bioorganic Chemistry Student: Mgr. Tomáš Eisner Supervisor: Assoc. Prof. PharmDr. Jaroslav Roh, Ph. D. Title of rigorosum thesis: Synthesis of novel cardioprotectants and metabolites of potent anticancer drug Bp4eT Anthracyclines (ANT) such as doxorubicin, daunorubicin, or epirubicin rank among the most effective anticancer drugs. However, their major side effect is chronic cardiotoxicity leading to irreversible cardiac damage and congestive heart failure. It is assumed that this side effect is caused by reactive oxygen species, whose formation is catalyzed by the complexes of anthracyclines with iron ions. The only clinically used drug preventing ANT cardiotoxicity is dexrazoxane (DXZ, Figure 1). In this work we dealt with the synthesis of novel DXZ analogues, because the structure-activity relationship studies have not been performed yet. The main analogue named ES-5 (Figure 1) was synthesized and its cardioprotective effect was evaluated both in vitro and in vivo. Fig. 1. Structures of DXZ and ES-5 Furthermore, thiosemicarbazone Bp4eT (2-benzoylpyridine 4-ethyl-3- thiosemicarbazone, Figure 2), a potent anticancer iron chelator and its metabolites were synthesized. These compounds were used as standards in metabolic...
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Synthesis of novel cardioprotectants and metabolites of potent anticancer drug - Bp4eT
Eisner, Tomáš ; Roh, Jaroslav (advisor) ; Zimčík, Petr (referee)
Charles University Faculty of Pharmacy Hradec Králové Department of Organic and Bioorganic Chemistry Student: Mgr. Tomáš Eisner Supervisor: Assoc. Prof. PharmDr. Jaroslav Roh, Ph. D. Title of rigorosum thesis: Synthesis of novel cardioprotectants and metabolites of potent anticancer drug Bp4eT Anthracyclines (ANT) such as doxorubicin, daunorubicin, or epirubicin rank among the most effective anticancer drugs. However, their major side effect is chronic cardiotoxicity leading to irreversible cardiac damage and congestive heart failure. It is assumed that this side effect is caused by reactive oxygen species, whose formation is catalyzed by the complexes of anthracyclines with iron ions. The only clinically used drug preventing ANT cardiotoxicity is dexrazoxane (DXZ, Figure 1). In this work we dealt with the synthesis of novel DXZ analogues, because the structure-activity relationship studies have not been performed yet. The main analogue named ES-5 (Figure 1) was synthesized and its cardioprotective effect was evaluated both in vitro and in vivo. Fig. 1. Structures of DXZ and ES-5 Furthermore, thiosemicarbazone Bp4eT (2-benzoylpyridine 4-ethyl-3- thiosemicarbazone, Figure 2), a potent anticancer iron chelator and its metabolites were synthesized. These compounds were used as standards in metabolic...
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Aminobisphosphonates and their derivatives: Traditional uses and novel applications
Eisner, Tomáš ; Roh, Jaroslav (advisor) ; Vávrová, Kateřina (referee)
Charles University in Prague Faculty of Pharmacy Hradec Králové Department of Inorganic and Organic Chemistry Student: Tomáš Eisner Supervisor: PharmDr. Jaroslav Roh, Ph. D. Specialized supervisor: Petri Turhanen, Ph. D. Title of diploma thesis: Aminobisphosphonates and their derivatives: Traditional uses and novel applications Bisphosphonates (BPs) are limited in therapeutical use because of their poor bioavailability after oral administration. Typically less than 1% is absorbed. Second limitation of treatment connected with BPs is the incidence of upper gastrointestinal tract irritation (2-10% cases). The aim of this work was the synthesis of new derivatives of aminobisphosphonate alendronate (ALN) with improved pharmacological properties which could be potentially used as a prodrug. ALN is used in clinical practice primarily to treat postmenopausal osteoporosis. The synthetic route leading to protected aminobisphosphonate derived from ALN was revised and optimized for large scale synthesis. The products of this route were needed for continuation in the preparation of new derivatives. Copper catalyzed ''click'' reaction of terminal alkyne and azidoBP was used with different starting materials to get a new possible prodrugs. Reaction of propargyl alcohol and azidoBP with Cu powder as a catalyst...
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The condition survey and the use of sports facilities in primary schools in Prague 6
Eisner, Tomáš ; Šíma, Jan (advisor) ; Janák, Vladimír (referee)
Title: The condition survey and the use of sports facilities in primary schools in Prague 6 Objectives: Based on a given project from municipal district of Prague 6 prepare the condition survey and the use of sports facilities in primary schools in Prague 6. Methods: In the paper are used methods of structured interview and use of secondary information. Results: Primary Schools in Prague 6 effectively using their physical education facilities at a time when there are no lessons and offer it the people, but it is limited insufficient capacity or inadequate functionality of the physical education facilities. Key words: sports facilities, physical education, primary school, Prague 6
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Role of radiological assistant by angiografic procedures
EISNER, Tomáš
Angiography as an X - ray examination of blood vessels showed an expressive development since its creation. From translumbal puncture of the abdominal aorta up to more tender Seldinger technique it led to considerable decrease of occurrence of peripro-cedural complications. Angiographic interventions and involved materials, instrumenta-tion devices and image processing possibilities are expressively improving. Invasive an-giopraphic examinations are substituted by non-invasive interventions like ultrasonogra-phy, magnetic resonance or computer tomography. After all they remain integral part of examination algorithms, especially by vessels interventions. A common note of invasive procedures in Cath-lab - in addition to diagnostics also by an intravascular ultrasonography or by therapeutical procedures like percutaneous transluminal angioplasty, stent implantation, vessels embolisation, trombolysis and trombectomy and other {--} is using of fluoroscopy with ionizing radiation and intravascular application of a contrast medium. Radiologic assistant has its more and more unsubstitutable role by diagnostic im-aging of vessels. Radiologic assistant has to be familiar with course of single intervention and with sequence of doctor{\crq}s operations, in order to be able to fulfill his requirements in time and at the same time he has to understand possible risk of complication's and he has to know how to respond to them properly and in time. Further he must well manage an-giography device and all its parts and know postprocessing picture adjustment. Quality work of radiologic assistant should have fundamental influence on dose of ionizing radiation for patient and for examining staff and on consumption and risks of application of contrast medium. By my own experiences with assistance by 4 628 non-coronary and 14 620 coro-nary angiographic examinations in last 10 years (1997-2006) I found set of 40 patients who were examined by pulse and continual fluoroscopy during angiography of lower limbs arteries at Cardio angiographic department of Faculty hospital in Motol. Conclusions make out advantage of pulse fluoroscopy, of digital postprocessing of images iclusive of 3D imaging and they confirmed hypothesis of ionizing radiation{\crq}s dose and carload of contrast medium. By conclusions of this work I suggest to take care of new imaging technics by invasive digital angiography and insert these knowledges to system of lifelong learning of radiologic assistants.
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