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Synthesis of ceramide NS using Grubbs metathesis
Obrdlík, Daniel ; Vávrová, Kateřina (advisor) ; Karabanovich, Galina (referee)
Ceramides are group of lipids which belong to sphingolipids. Skin ceramides have several functions in the organisms. They are important part of the lipid matrix of the stratum corneum, the outermost layer of the epidermis, where they participate in the barrier function of the skin. Furthermore, ceramides are secondary messengers in cell apoptosis and participate in many metabolic processes. Ceramides are composed of sphingoid base, which is N-acylated by fatty acid. Sphingoid base can be sphingosine, phytosphingosine, dihydrosphingosine or 6- hydroxysphingosine. Lower level of ceramides in the stratum corneum is associated with various skin diseases especially atopic dermatitis and psoriasis. Manifestations of these diseases is significantly improved by topical administration of ceramide. Exogenously administered ceramides help regenerate damaged skin and improve hydration of the skin. However, it is not fully known, in which way topically administered ceramides improve the progress of diseases. The aim of this work is synthesize physiological ceramide NS by using Grubbs metathesis reactions and optimize the conditions for achieving the highest yields. Synthesis of ceramide NS was based on pentadecan-1-ol, which was eliminated to terminal alkene. The elimination was carried out in three different...
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Synthesis and structure-antimycobacterial activity relationship study of dinitrobenzylsulfanyl heteroaromates
Karabanovich, Galina ; Hrabálek, Alexandr (advisor) ; Zimčík, Petr (referee) ; Sedlák, Miloš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Ing. Galina Karabanovich Supervisor: Prof. PharmDr. Alexandr Hrabálek, CSc. Consultant: PharmDr. Jaroslav Roh, Ph.D. Title of PhD thesis: Synthesis and structure-antimycobacterial activity relationship study of dinitrobenzylsulfanyl heteroaromates This thesis deals with the design and synthesis of novel heterocyclic compounds with high and selective antimycobacterial activity and the structure - antimycobacterial activity relationship study of these compounds. The history of knowledge about Tuberculosis, drug/regimen development, a way to successfully understand the Mycobacterium tuberculosis (M.tb.) etiology and the search for suitable therapy for treatment of drug-susceptible and drug-resistant TB are described in chapters 2 and 3. The current situation of TB epidemic and efforts towards its solution are also included. In chapter 4, the structure of mycobacterial cell wall is presented. It demonstrates the mycobacterial structural feature possessing an unusual, highly protective properties, which is essential for M.tb. growth and its survival in the host. The synthesis, logical consistency of structural changes and the results of antimycobacterial evaluation of prepared...
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Design and synthesis of potential M1 muscarinic acetylcholine receptor dualsteric modulator
Průša, Petr ; Roh, Jaroslav (advisor) ; Karabanovich, Galina (referee)
Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Inorganic and Organic chemistry Consultant: Prof. Dr. Ulrike Holzgrabe, PharmDr. Jaroslav Roh, Ph.D. Student: Petr Průša Title of Thesis: Design and synthesis of potential M1 muscarinic acetylcholine receptor dualsteric modulator Dualsteric ligands can modulate activity of receptors connected with G-proteins, also known as G- protein coupled receptor. These ligands are interesting for their use as pharmacological tools to clarify activity-induced conformational transitions. Moreover, dualsteric ligands can serve like a concept for design of new drugs. It was already prove that dualsteric compounds containing orthosteric ligand, which can act as agonist or antagonist, and allosteric part, which act as address determining target receptor via own selectivity, have affected affinity to receptor. Further, dualsteric binding can serve to introduce receptor subtype selectivity. Muscarinic acetylcholine receptors are related to G-proteins. Until now five subtypes of these receptors (usually marked as M1 - M5) are known. Activation of single muscarinic acetylcholine receptors subtypes induce different replies. Muscarinic acetylcholine receptors are widely represent in entire organism and are important targets for some drugs....
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