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Preparation and evaluation of new potential antimicrobial drugs and prodrugs
Imramovský, Aleš ; Vinšová, Jarmila (advisor) ; Kríž, Miroslav (referee) ; Pazdera, Pavel (referee)
5. SUMMARY This thesis deals with the synthesis of antimicrobial active compounds from the group of salicylanilide derivates that were found to be highly antituberculosis active compounds against atypical and resistant strains of Mycobacterium tuberculosis. These derivates served as the starting substances for the synthesis of prodrugs of acetic acid and amino acid esters, with the aim to reduce toxicity and to optimize physico-chemical properties and transport to the site of action. The second group under investigation was new modifications of some contemporary antituberculosis drug (isoniazide and pyrazinamide), the combination of either of these two compounds with second active molecule through an easily splitting methane bridge, which together could serve as depot forms, after release of both parts they may act as synergists. The outcomes of a literary search, that forewent synthesis, were published as survey articles in scientific papers. They deal with: a) cyclization forms of prodrugs (paper I), b) salicylanilides and their research trends (paper II) and c) isoniazide, its mechanism of activity and structure modifications published till now (paper V). The main scope of the thesis is experimental parts whose results were parcially published and belong to enclosed articles (paper III, IV and VI)....
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