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Synthesis of purine derivatives with potential antimycobacterial activity
Finger, Vladimír ; Roh, Jaroslav (advisor) ; Doležal, Martin (referee) ; Brulíková, Lucie (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Doctoral Degree Program Bioorganic Chemistry Candidate: Ing. Vladimír Finger Supervisor: Assoc. Prof. PharmDr. Jaroslav Roh, Ph.D. Title of Doctoral Thesis: Synthesis of purine derivatives with potential antimycobacterial activity The theoretical part of this dissertation briefly summarizes basic data on tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb.). The epidemiological data published in the annual report of the World Health Organization (WHO) and the structure of drugs used in current TB therapy are presented. The theoretical section also gives a brief overview of the treatment of TB and mentions four compounds that are currently in phase II clinical trials. The mechanism of action of these compounds is inhibition of the enzyme decaprenylphosphoryl-β-D-ribose-2'-epimerase, specifically the DprE1 subunit. This enzyme plays an important role in the synthesis of mycobacterial call wall. The next part of the dissertation summarizes the results of research on potential purine and pyrrolo[3,2- d]pyrimidine antituberculosis agents derived from purine-6-one 10. Compound 10 was identified as derivative with moderate anti-TB activity (MIC99(Mtb) = 4 μM) in a high-...
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Synthesis and evaluation of potential antimicrobial drugs
Pflégr, Václav ; Krátký, Martin (advisor) ; Doležal, Martin (referee) ; Brulíková, Lucie (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Organic and Bioorganic Chemistry Doctoral Degree Program Bioorganic Chemistry Candidate: Mgr. Václav Pflégr Supervisor: doc. PharmDr. Mgr. Martin Krátký, Ph.D. Title of Doctoral Thesis: Synthesis and evaluation of potential antimicrobial drugs The dissertation thesis reports some results achieved within the framework of a doctoral project dealing with the synthesis and evaluation of potential antimicrobial drugs. The main goal was to obtain new derivatives of isoniazid and its analogues acting against Mycobacterium tuberculosis and non-tuberculous mycobacteria, optimally including resistant strains. A partial aim was the preparation of peptide carriers for antituberculosis drugs, which, in addition to the development of new molecules, is another promising direction for the development of new therapeutic strategies against tuberculosis. The theoretical part of the dissertation overviews the issue of tuberculosis. The aetiology of the disease, the morphology of the cell wall of mycobacteria and selected epidemiological data are presented there. The treatment and characteristics of clinically used drugs are described in detail, this chapter is followed by a brief research review of promising clinically evaluated...
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Synthesis, reactivity and biological activity of C5 substituted uracil analogues
Brulíková, Lucie ; Holý, Antonín (advisor) ; Rosenberg, Ivan (referee) ; Moravcová, Jitka (referee)
Bibliographical identification: Author's first name and surname: RNDr. Lucie Brulíková (nee Spáčilová) Title: Synthesis, reactivity and biological activity of C-5 substituted uracil analogues Type of thesis: Ph.D. thesis Department: Department of Organic Chemistry, Faculty of Science, Palacký University Olomouc Advisor: prof. RNDr. Antonín Holý, Dr.Sc., Dr.hc. mult. Advisor-consultant: doc. RNDr. Jan Hlaváč, Ph.D. The year of presentation: 2011 Abstract: The presented thesis is focused on the synthesis of various C-5 modified uracil analogues, the study of their reactivity and biological activity, especially cytotoxic activity. In the first part, the brief survey of described results for selected 5-alkoxymethyluracil analogues is performed. The second part of the presented thesis deals with the synthesis of novel uracil analogues modified at the C-5 position, the development and optimizing of procedure leading to the desired compounds, the study of biological activity and the evaluation of structure- activity relationship (SAR). This part presents the synthesis of a series of 5-[alkoxy(4- nitrophenyl)methyl)]uracil and 5-alkoxymethyluracil analogues and extended SAR studies depending on a substitution of metylene bridge directly attached at the C-5 position as well as alkoxy chain length. The last part of...
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Synthesis, reactivity and biological activity of C5 substituted uracil analogues
Brulíková, Lucie ; Holý, Antonín (advisor) ; Rosenberg, Ivan (referee) ; Moravcová, Jitka (referee)
Bibliographical identification: Author's first name and surname: RNDr. Lucie Brulíková (nee Spáčilová) Title: Synthesis, reactivity and biological activity of C-5 substituted uracil analogues Type of thesis: Ph.D. thesis Department: Department of Organic Chemistry, Faculty of Science, Palacký University Olomouc Advisor: prof. RNDr. Antonín Holý, Dr.Sc., Dr.hc. mult. Advisor-consultant: doc. RNDr. Jan Hlaváč, Ph.D. The year of presentation: 2011 Abstract: The presented thesis is focused on the synthesis of various C-5 modified uracil analogues, the study of their reactivity and biological activity, especially cytotoxic activity. In the first part, the brief survey of described results for selected 5-alkoxymethyluracil analogues is performed. The second part of the presented thesis deals with the synthesis of novel uracil analogues modified at the C-5 position, the development and optimizing of procedure leading to the desired compounds, the study of biological activity and the evaluation of structure- activity relationship (SAR). This part presents the synthesis of a series of 5-[alkoxy(4- nitrophenyl)methyl)]uracil and 5-alkoxymethyluracil analogues and extended SAR studies depending on a substitution of metylene bridge directly attached at the C-5 position as well as alkoxy chain length. The last part of...
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