diplomsko delo
Marcel Tušek (Avtor), Marko Novinec (Mentor)

Povzetek

Pirazol in njegovi derivati postajajo vse bolj pomembni v svetu medicine zaradi svojega dokazanega protimikrobnega delovanja. Razvoj različnih derivatov povečuje verjetnost, da bodo nekateri uporabni pri razvoju novih antibiotikov. Derivat pirazola, 4‑(2‑aminoetil)-1-(piridin-2-il)-1H-pirazol-5-ol (I1), zavira rast bakterije Escherichia coli in inhibira aktivnost encima L-treonin dehidrogenaza (TDH). Ta encim je ključnega pomena za metabolizem aminokislin in tvorbo biofilma. TDH v človeku nima funkcionalnega homologa, zato bi lahko spojina I1 bila osnova za razvoj novih antibiotikov. Cilj raziskovalnega dela je bil preučiti, kako različni derivati pirazola vplivajo na inhibicijo aktivnosti TDH in ali vplivajo tudi na tvorbo biofilmov. Za delovanje encima je potreben kofaktor NAD+, ki se ob reakciji pretvori v NADH, kar omogoča fluorimetrično spremljanje aktivnosti. Uporabili smo rekombinantni TDH ter spremljali njegovo aktivnost v prisotnosti različnih derivatov pirazola. Med testiranimi derivati je bil najbolj potenten derivat I1. Podobno inhibitorno aktivnost je imel tudi derivat I2, vendar njegova slaba topnost ni omogočila testiranja pri višjih koncentracijah. Preizkusili smo tudi vpliv derivatov na tvorbo biofilmov, pri čemer smo ugotovili, da vsi derivati zavirajo tvorbo biofilmov. Le I1 in I2 pa sta delovala neposredno na aktivnost TDH. Na podlagi tega ne moremo z gotovostjo potrditi povezave med inhibicijo TDH in zaviranjem tvorbe biofilma.

Ključne besede

L-treonin dehidrogenaza;biofilmi;derivati pirazola;Michaelisova konstanta;diplomska dela;

Podatki

Jezik: Slovenski jezik
Leto izida:
Tipologija: 2.11 - Diplomsko delo
Organizacija: UL FKKT - Fakulteta za kemijo in kemijsko tehnologijo
Založnik: [M. Tušek]
UDK: 577.15:547.77(043.2)
COBISS: 243067651 Povezava se bo odprla v novem oknu
Št. ogledov: 106
Št. prenosov: 49
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Angleški jezik
Sekundarni naslov: Characterisation of the threonine dehydrogenase inhibition with specific derivatives of pyrasole
Sekundarni povzetek: Pyrazole and its derivatives are becoming increasingly prevalent in medicine due to their proven antimicrobial activity. The development of new derivatives increases the likelihood of discovering new effective antibiotics. The pyrazole derivative, 4-(2-aminoethyl)-1-(pyridine-2-yl)-1H-pyrazole-5-ol (I1), inhibits the growth of Escherichia coli and L-threonine dehydrogenase (TDH) activity. The enzyme is a key component in amino acid metabolism and biofilm formation. TDH is not present in humans nor does it have a homologous protein in humans, hence I1 could be a potential base for new drug development. The aim of the research project was to examine the different types of pyrazole derivatives and their effects on TDH activity and whether they affect the formation of biofilms. For the enzyme to work, the cofactor NAD+ is required, where upon the reaction is converted into NADH, which then makes it possible for fluorometric detection of activity. Among the tested derivatives, I1 was the most promising and potent. Derivative I2 also had similar inhibitory activity. However, due to its poor solubility, it proved impossible to test at higher concentrations. Tests were also conducted to see the impact derivatives have on biofilm formation, and the results showed that all derivatives inhibit biofilm formation. However, only I1 and I2 directly affect TDH activity. Based on these findings, further research is required to establish with certainty to prove the correlation between TDH inhibition and biofilm formation suppression.
Sekundarne ključne besede: L-threonine dehydrogenase;biofilms;pyrazole derivatives;Encimi;Encimski inhibitorji;Pirazoli;Univerzitetna in visokošolska dela;
Vrsta dela (COBISS): Diplomsko delo/naloga
Študijski program: 1000371
Komentar na gradivo: Univ. v Ljubljani, Fak. za kemijo in kemijsko tehnologijo, UNI Biokemija
Strani: 1 spletni vir (1 datoteka PDF (40 str.))
ID: 26719441