National Repository of Grey Literature 82 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Synthesis of lansoprazole analogs with potential antimycobacterial activity
Kubásková, Mária ; Roh, Jaroslav (advisor) ; Krátký, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Mária Murínová Supervisor: doc. PharmDr. Jaroslav Roh, Ph.D. Title of diploma thesis: Synthesis of lansoprazole analogs with potential antimycobacterial activity Mycobacterium tuberculosis is a bacterium that causes a serious infectious disease, tuberculosis. Recent studies show an increase in the number of patients suffering from this disease, pointing to the increasing resistance of this bacterium to most antibiotics. Given the current globalization of the world, as another factor contributing to the spread of tuberculosis in areas where the disease has been under control so far, it is essential to focus on the development of new antituberculosis drugs. Recent studies have reported that a promising candidate is lansoprazole, which is known primarily as gastric proton pump inhibitor. The mechanism of the antimycobacterial effect is that lansoprazole, after intracellular reduction to lansoprazole sulfide, kills M. tuberculosis by inhibiting cytochrome bc-1. This makes lansoprazole sulfide an excellent compound for further structural optimization and study of its structure-activity relationships. The aim of this work was to modify the structure of the lansoprazole and to prepare its...
Preparation and Evaluation of New Ligands Targeting Organic Cation Transporters in the Central Nervous System for the Treatment of Depression
Monteiro, Andrea ; Roh, Jaroslav (advisor) ; Vávrová, Kateřina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Student: Andrea Monteiro Supervisor: Assoc. Prof. PharmDr. Jaroslav Roh, Ph.D. Specialized supervisors: Nicolas Pietrancosta, Ph.D. Sophie Gautron, Ph.D. Title: Preparation and Evaluation of New Ligands Targeting Organic Cation Transporters in the Central Nervous System for the Treatment of Depression Brain organic cation transporters (OCT2, OCT3) are polyspecific facilitated diffusion transporters that regulate aminergic tonus and have a complementary role to high-affinity monoamine transporters (serotonine transporter SERT, noradrenaline transporter NET and dopamine transporter DAT) in monoamine clearance in the brain. Their complementary characteristics compared to the high-affinity transporters (widespread distribution, broader pharmacological profile) and their involvement in mood-related functions make brain OCT relevant and original targets for the development of novel antidepressants. H2-cyanome is a newly developed prodrug of cyanome that targets OCT. This prodrug showed promising antidepressant efficacy in a rodent model of chronic depression. Despite the positive impact of this prodrug on antidepressant efficacy, its limitation is its high affinity for 1 adrenergic receptors that may...
Quantification of skin ceramides in patients after oncological treatment
Voláková, Eliška ; Opálka, Lukáš (advisor) ; Roh, Jaroslav (referee)
Charles University, Faculty of pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Eliška Voláková Supervisor: PharmDr. Lukáš Opálka, Ph.D. Title of diploma thesis: Quantification of skin ceramides in patients after oncological treatment Ceramides are one of the three basic lipid components present in the stratum corneum of human skin. Alterations in the ratio of individual ceramides are associated with disruption of skin barrier function. Such changes have been observed not only in skin diseases of the non-cancerous type, but also as a consequence of cancer. The main aim of the present study was to investigate the difference in the representation of skin ceramides in the stratum corneum of healthy patients and patients after cancer. Samples were collected from five groups of patients, four of which represented cancer patients with different types of treatment: tumor resection, chemotherapy, radiation or a combination of chemotherapy and radiation. The remaining fifth group consisted of control samples from volunteers without a diagnosis of cancer. Samples were obtained by tape-stripping from an identical site on patient forearm, followed by protein determination. Cancer patient samples were compared with control samples in terms of different water loss through the...
Synthesis of protein-kinase inhibitors as a potential treatment of cancer
Merdita, Sara ; Roh, Jaroslav (advisor) ; Karabanovich, Galina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry in collaboration with Biomedical Research Center UH HK Author: Sara Merdita Supervisor: Assoc. Prof. PharmD. Jaroslav Roh, PhD. Advisors: PharmD. Lukáš Górecki, PhD.; Assoc. Prof. PharmD. Jan Korábečný, PhD. Title of diploma thesis: Synthesis of protein-kinase inhibitors as a potential treatment for cancer Cancer is one of the leading causes of fatalities worldwide, which is attracting attention of many researchers with desire to develop treatments that selectively target cancerous cells while simultaneously sparing healthy cells. The main overall strategy is to exploit features specific to cancer - the cancer hallmarks. Those are represented, for instance, by genomic instability and aberrant DNA damage response (DDR) pathways. The DDR consists of cascades of kinases and other proteins and messengers, where we highlighted the synthetic lethal interaction between the kinases ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related). The two are major driving forces in the DDR, where in cancer ATM tends to be mutated and therefore dysfunctional, making the cells' viability reliant on ATR. Thus, ATR inhibition makes a particularly attractive strategy for abrogating cancer survival without...
Synthesis and study of hyaluronic acid derivatives modified on carboxyl
Volfová, Gabriela ; Roh, Jaroslav (advisor) ; Opálka, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Author: Gabriela Volfová Supervisors: Mgr. Radovan Bu a, Ph.D. doc. PharmDr. Jaroslav Roh, Ph.D. Title: Synthesis and study of hyaluronic acid derivatives modified on carboxyl Abstract: Hyaluronic acid (HA) is a naturally occurring linear polysaccharide. Due to its biocompatibility and non-immunogenicity, HA and its derivatives are widely used in various biological and medical applications. The e cacy of each formulation is strongly related to the molecular weight (MW) of the HA used. Unfortunately, various factors can a ect the MW during the manufacturing process. Elevated tem- perature required during the sterilization process is one significant example, which can lead to a reduction in molecular weight and result in a loss of some desired properties of the final product. This work focuses on the synthesis of HA amides formed on its free carboxyl group and subsequently studying the e ect of this modifi- cation on the degradation rate at elevated temperature. Three final compounds were prepared by reacting HA with various amines using 4-(4,6-dimethoxy-1,3,5-triazin-2- yl)-4-methylmorpholinium chloride (DMTMM), all of which underwent degradation noticeably faster than native HA.
Synthesis of cardioprotective ion chelators derived from diethylenetriaminepentaacetic acid
Šůs, Jan ; Roh, Jaroslav (advisor) ; Špulák, Marcel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Student: Mgr. Jan Šůs Supervisors: Assoc. Prof. PharmDr. Jaroslav Roh, Ph. D. Title of rigorosum thesis: Synthesis of cardioprotective ion chelators derived from diethylenetriaminepentaacetic acid Anthracyclines (ANTs) such as doxorubicin or daunorubicin are widely used anticancer drugs. However, their administration is associated with high risk of cardiotoxicity. Chronic ANT cardiotoxicity is characterized by dilated cardiomyopathy, with subsequent development of left ventricular contractile dysfunction and congestive heart failure. It is supposed that the complexation of ANTs with intracellular iron ions leads to the formation of reactive oxygen species, which causes serious tissue damage especially in myocardium. However, recent studies showed that the mechanism of action is more complex and the inhibition of topoisomerase IIβ (TOP2β) may play a crucial role. The only drug preventing cardiotoxicity of ANTs with established clinical efficacy is dexrazoxane (DEX). The mechanism of action of DEX is not fully elucidated, it probably involves either chelation of intracellular ions by its metabolite ADR-925 (Fig. 1) or the inhibition of TOP2β by the parent compound. Fig. 1. Dexrazoxane and its...
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...
Synthesis of novel cardioprotective iron chelators
Hrušková, Kateřina ; Vávrová, Kateřina (advisor) ; Roh, Jaroslav (referee)
Oxidative stress participates in patophysiology of many serious cardiovascular diseases. Free intracellular iron occurs as a catalyst of Haber-Weiss and Fenton reaction between superoxides and peroxides increasing the formation of highly toxic hydroxyl radicals, which cause cell damage. Iron chelators diminish the pool of free iron and thus become perspective agents in therapy of various diseases, e.g. anthracycline-induced cardiotoxicity. Aroylhydrazones group, such as salicylaldehyde-isonicotinoylhydrazone (SIH), appear to be highly efficient chelators. Unfortunately, pharmacokinetic studies focused on these compounds revealed their low stability in plasma. Therefore, I synthesised a series of SIH analogs in order to increase their stability together with preserving the ability to chelate free intracellular iron and to define their structure-activity relationships. A basic hypothesis in design of the novel chelators was using substituted ketone instead of aldehyde, leading potentially to an enhanced stability of hydrazone bond. SIH Two different methods were used during the reactions, a conventional heating in an oil bath and heating in a microwave reactor. The latter caused a significant shortening of the reaction time. In vitro studies of novel compounds showed their higher stability in plasma,...
Synthesis of new types of succinimides as a potential adjuvant
Božiková, Slavomíra ; Roh, Jaroslav (advisor) ; Opálka, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Student: Slavomíra Božiková Supervisor: doc. PharmDr. Jaroslav Roh, Ph.D. Consultant: RNDr. Dávid Maliňák, PhD Title of Diploma Thesis: Synthesis of new types of succinimides as a potential adjuvant Adjuvants represent a big group of the compounds used for the increased immune response to vaccines. This whole concept of these helper substances is more than 80 years old. The first finding that started the research of more substances was the alternative system of the aluminium salt. Important group of adjuvants are substances, which activate the immunity system to increased reaction after stimulation of toll-like receptors (TLRs) that are present in the human body. These receptors are considered as one of the most important immunity molecules. The best examined receptors of this group is the TLR4 receptor that binds various ligands. The most important ligands are the lipopolysaccharide of Gram-negative bacteria. Mechanisms of the interaction of these ligands with TLR4 are being examined recently. In my thesis I focused on the TLR4 receptors and on the synthesis of new molecules of the succinimide type, which eventually can stimulate these receptors and be potential adjuvants.

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1 Roh, Jan
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