Biosinteza, razvoj in uporaba antraciklinskih protirakastih učinkovin v medicini

Snedec, Tadeja (avtor), Petković, Hrvoje (mentor)

Antraciklini so obsežna skupina protirakastih učinkovin, katerim je skupno osnovno tetraciklinsko okostje. Prva derivata antraciklinov, doksorubicin in daunorubicin, sta bila izolirana iz kulture bakterije Streptomyces peucetius že v zgodnjih šestdesetih letih prejšnjega stoletja. Učinkovine iz skupine antraciklinov proizvaja mnogo bakterij rodu Streptomyces, med katerim kot glavni proizvodni organizem antraciklinov ostaja S. peucetius. Antraciklini se uporabljajo za zdravljenje različnih oblik raka, kot so rak pljuč, prostate, različne vrste levkemije, osteogeni kostni tumor in Hodgkinov limfom. Najpogosteje pa za zdravljenje raka dojk in akutne mieloidne levkemije. Vendar pa je njihova uporaba v klinični praksi omejena zaradi močnih stranskih učinkov, kot je kardiotoksičnost, ki se kaže kot subklinično zmanjševanje funkcije levega srčnega prekata ali očitne kardiomiopatije. Glavni mehanizmi delovanja antraciklinov so reverzibilna interkalacija v DNA, nastanek prostih radikalov, vezava in alkilacija DNA, zamreženje DNA, razvijanje ali separacija verig DNA, direkten vpliv na membrano ter indukcija apoptoze. Od mnogih načinov delovanja antraciklinov sta primarni molekularni tarči delovanja DNA topoizomeraza ter reverzibilna interkalacija v DNA. Z namenom zmanjševanja stranskih učinkov in povečanja biološke aktivnosti antraciklinov se tem molekulam pogosto s postopki polsintezne kemije dodaja fluor ali dušikove spojine, pogosta pa je tudi zamenjava sladkornega ostanka na osnovnem tetraciklinskem skeletu. Poleg tega potekajo tudi raziskave novih načinov aplikacije teh potentnih učinkovin, kot so npr. priprava konjugatov s protitelesi, ter odkrivanje novih analogov antraciklina.

• Jezik: Slovenski jezik
• Ključne besede: biotehnologija, antraciklini, biosinteza, razvoj, uporaba, medicina
• Vrsta gradiva: Diplomsko delo/naloga
• Tipologija: 2.11 - Diplomsko delo
• Organizacija: BF - Biotehniška fakulteta
• Založnik: [T. Snedec]
• Leto izida: 2017
• PID: 20.500.12556/RUL-95654
• UDK: 606:61:602.4:602.3:579.873.7(043.2)
• COBISS.SI-ID: 8811641
• Datum objave v RUL: 21.09.2017

SNEDEC, Tadeja, 2017, Biosinteza, razvoj in uporaba antraciklinskih protirakastih učinkovin v medicini [na spletu]. Diplomsko delo. T. Snedec. [Dostopano 18 maj 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=95654

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Biosynthesis, development and use od anthracycline anticancer substances in medicine

Izvleček

Anthracyclines are a large group of anticancer compounds whose common characteristic is a basic tetracyclic skeleton. The first derivatives of antracycline, doxorubicin and daunorubicin, were isolated from the culture of Streptomyces peucetius in the early 1960s. The main producer of anthracyclines remains S. peucetius, but these natural products can be produced by a broad spectrum of Streptomyces species. Anthracyclines are used to treat various forms of cancer, such as lung cancer, prostate cancer, various types of leukaemia, osteogenic bone tumours and Hodgkin's lymphoma, but are most commonly used to treat breast cancer and acute myeloid leukaemia. However, their use in clinical practice is limited due to the adverse side effects, such as cardiotoxicity. Cardiotoxicity is manifested as subclinical reduction of the functions of the left heart ventricle or obvious cardiomyopathy. The main mechanisms of action of anthracyclines are reversible intercalation into DNA, formation of free radicals, binding and alkylation of DNA, DNA cross-linking, separation of DNA chains, direct effect on the membrane and induction of apoptosis. The primary molecular targets of anthracyclines are DNA topoisomerases and reversible intercalation into DNA. In order to reduce the side effects and increase the biological activity of the anthracyclines, fluorine or nitrogen atoms are often added to the basic tetracycline sceleton and. the sugar moiety can also be modified. In addition, antracycline have been studied, for different applications and a lot of efforts are directed towards screening of novel anthracycline analogues.

• Ključne besede: biotechnology, anthracycline, biosynthesis, development, use, medicine