Faculty of Pharmacy, Lj. (FFALJ)
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Zaviralci bakterijske DNA giraze A z 1,5-naftiridinskim skeletom in merjenje njihovega protibakterijskega učinka = DNA Gyrase A inhibitors with 1,5-naphthyridine scaffold and measurement of their antibacterial effect : enoviti magistrski študijski program FarmacijaHuzjak, Tilen, 1995-Glede na mehanizem delovanja protimikrobnih učinkovin ločimo več skupin - eno sestavljajo take, ki delujejo na celične procese spreminjanja DNA. V to uvrščamo tudi nove zaviralce podenote A ... bakterijske DNA-giraze, imenovane NBTI (angl. novel bacterial topoisomerase inhibitors). Topoizomeraze tipa II, kamor spada tudi DNA-giraza, so encimi, ki cepijo obe verigi DNA in tako katalizirajo uvajanje supernavojev ali sproščanje topološke napetosti, kar je pomembno pri shranjevanju genskega materiala in procesih transkripcije, rekombinacije in replikacije. Z zaviranjem tega encima NBTI dosegajo protibakterijski učinek. NBTI so sestavljeni iz levega dela, ki tvori interakcije z DNA, desnega dela, ki se veže v hidrofobni žep DNA-giraze, in distančnika, ki povezuje oba dela in je odgovoren za njuno pravilno usmeritev. V sklopu eksperimentalnega dela magistrske naloge smo z virtualnim rešetanjem in molekulskim sidranjem najprej poiskali in določili nove potencialne NBTI. Načrtovali in kasneje sintetizirali smo molekulske strukture z ohranjenim 1,5-naftiridinskim levim delom in 4-amino-1-etilpiperidinskim distančnikom. Za desni del molekule smo v prvi seriji uporabili različne mono- in disubstituirane aromatske biciklične fragmente, v drugi seriji pa monociklične. Pripravljene spojine smo karakterizirali s tekočinsko kromatografijo, z različnimi spektroskopskimi tehnikami in merjenjem tališč. Sledilo je vrednotenje zaviralnega učinka potencialnih NBTI z določanjem srednje inhibitorne koncentracije IC50 na izoliranih tipih DNA-giraze Staphylococcus aureus in Escherichia coli ter minimalne inhibitorne koncentracije MIC na obeh omenjenih bakterijah ter številnih drugih bakterijskih sevih. Z dobljenimi rezultati smo potrdili in ponovno orisali vpliv znane razlike v velikosti vrzeli v aktivnem mestu DNA-giraze v S. aureus in E. coli na spekter delovanja NBTI ter razširili nabor potencialnih protibakterijskih spojin z nekaj obetavnimi fluorosubstituiranimi molekulami, ki omogočajo vpogled v možnost tvorbe koristnih fluoro-DNA giraza interakcij.Type of material - master's thesis ; adult, seriousPublication and manufacture - Ljubljana : [T. Huzjak], 2020Language - slovenianCOBISS.SI-ID - 28364035
Author
Huzjak, Tilen, 1995-
Other authors
Anderluh, Marko
Topics
DNA-giraza |
topoizomeraze |
protibakterijske učinkovine |
naftiridin |
sinteza učinkovin |
sintezni postopki |
virtualno rešetanje
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Knjižnica emšf 0000000543 HUZJAK TILEN Zaviralci 0000000881 IN: 0016695 Knjižnica emšf 543 HUZJAK TILEN Zaviralci 881 IN: 0016695 |
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Huzjak, Tilen, 1995- | 56114 |
Anderluh, Marko | 21456 |
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