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Influence of benzoxazinedione derivatives on selected mycobacterial enzymes
Švidrnochová, Michaela ; Novotná, Eva (advisor) ; Krátký, Martin (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Michaela Švidrnochová Supervisor: RNDr. Eva Novotná, Ph.D. Title of Thesis: Influence of benzoxazinedione derivatives on selected mycobacterial enzymes Tuberculosis is an insidious infectious disease with more and more increasing incidence in certain regions. It is difficult to treat by the available means because of increasing cases of multidrug resistance, which is defined as a resistance of M. tuberculosis at least to two primary antituberculotic drugs - rifampicin and isoniazid. That's why is necessary to search for new substances which interfere with the metabolic pathways of Mycobakterium tuberculosis. Enzyme inhibitions in different levels of these pathways are considered to be a target of the new potencial antituberculotic drugs. In this work, influence of monosulphur and disulphur derivatives of 3-(4-alkylphenyl)-2H- 1,3-benzoxazine-2,4(3H)-dione on enoyl-ACP-reductase, dihydrofolate reductase, isocitrate lyase and FtsZ was tested by thermal shift assay, spectrofotometric method and light scattering. The results showed that the dihydrofolate reductase is not a drug target of selected inhibitors. Isocitrate lyase was the most inhibited by sulphur derivative 3-(4-terc-...

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