magistrska naloga
Janja Ahej (Avtor), Stane Pajk (Mentor), Martina Hrast (Komentor)

Povzetek

Tuberkuloza je kronična nalezljiva bolezen, za katero vsako leto po vsem svetu na novo zboli približno devet milijonov ljudi. Povzroča jo bacil Mycobacterium tuberculosis, katerega posebnost je kompleksna celična stena. Eden izmed njenih ključnih gradnikov so mikolne kisline. InhA (2-trans-enoil-ACP reduktaza) je encim, ki v sistemu FASII sodeluje pri njihovi sintezi. Najpogosteje uporabljeno zdravilo v boju proti tuberkulozi je Izoniazid (INH), ki deluje kot zaviralec encima InhA. Za njegovo delovanje je ključen encim KatG, ki ga pretvori v aktivno obliko. V zadnjem desetletju se zaradi mutacij gena katG vse pogosteje pojavljajo na INH odporni sevi M. tuberculosis. Nove tarče učinkovitih inhibitorjev so tako neposredni zaviralci encima InhA, ki za svoje delovanje ne potrebujejo predhodne aktivacije z encimom KatG. V okviru magistrske naloge smo želeli sintetizirati pet derivatov, vendar smo le s tremi uspeli izpeljati sintezo do konca in jih testirati na zaviralno delovanje na encim InhA. Naše sintetizirane tri spojine zavirajo delovanje encima InhA v nizkem mikromolarnem območju. Čeprav najboljši zaviralci zavirajo InhA v nanomolarnem območju, te spojine predstavljajo dobro izhodišče za nadaljnjo sintezo in optimizacijo do potencialnih novih antituberkulotikov.

Ključne besede

mikrobakterijska celična stena;mikolna kislina;zaviralci InhA;sinteza spojin;

Podatki

Jezik: Slovenski jezik
Leto izida:
Tipologija: 2.09 - Magistrsko delo
Organizacija: UL FFA - Fakulteta za farmacijo
Založnik: [J. Ahej]
UDK: 616-002.5-008:615.2(043.3)
COBISS: 4628081 Povezava se bo odprla v novem oknu
Št. ogledov: 573
Št. prenosov: 124
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: Introduction of bioisosteric replacements of phenyl group at position 1 of the 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine type InhA inhibitors
Sekundarni povzetek: Tuberculosis is a chronic infectious disease which affects about nine million people each year around the world. It is caused by Mycobacterium Tuberculosis which is specific for its complex cell wall. One of its key building blocks are mycolic acids. InhA (2-trans-enoyl-ACP reductase) is an enzyme that is involved in the biosynthesis in the FASII system. The most commonly used medicament in the fight against tuberculosis is Isoniazid (INH), which acts as an InhA inhibitor. The key agent that makes Isoniazid effective is the KatG enzyme, which transforms it into an active form. Over the last decade, due to mutations in the katG gene Mycobacterium Tuberculosis resistance to INH has been increasing. New effective inhibitors are direct InhA inhibitors that block the target InhA without requiring bio-activation with the KatG enzyme. In the master thesis, we wanted to synthesize five derivatives, but we managed to completely synthesize only three of them and test them as inhibitors of the InhA. Our three synthesized compounds inhibit the activity of the InhA in the low micromolar range. Although the best inhibitors inhibit InhA is in the nanomolar range, these compounds provide a good starting point for further synthesis and optimization towards potentially new antituberculotics.
Sekundarne ključne besede: Tuberkuloza;Endokrinologija;
Vrsta dela (COBISS): Magistrsko delo/naloga
Komentar na gradivo: Univ. Ljubljana, Fakulteta za farmacijo
Strani: V, 58 f.
ID: 12025784