magistrsko delo
Povzetek
Odkritje protitumorske aktivnosti cisplatina in analogov, kot tudi njihova uspešna uporaba v medicini pri zdravljenju različnih tumorjev in pri simptomatskem zdravljenju Alzheimerjeve bolezni (AB), so znova obudili zanimanje za razvoj novih zdravil na osnovi platine in drugih kovin, npr. rutenija. Inhibicija acetilholinesteraze (AChE) in butirilholinesteraze (BChE) ima ugodni učinek pri pacientih z AB. Rezultat je povečana koncentracija acetilholina v sinaptični špranji, kar vodi v izboljšanje kognitivnih funkcij. Ekspresija glutation S transferaze (GST) je povečana v rakavih celicah, zato inhibitorji GST predstavljajo potencialne protitumorske učinkovine. V preteklih študijah so rutenijevi kompleksi pokazali dobro anti-AChE, anti-BChE in anti-GST aktivnost in kot taki potrdili možnost terapevtske uporabe pri blaženju simptomov AB in zdravljenju raka kot večtarčna zdravila. V študiji smo testirali 34 novo sintetiziranih rutenijevih spojin, njihovih prekurzorjev in ligandov na encimih živalskega in humanega izvora. Rezultati študije so pokazali, da imajo naši kompleksi majhno ali zmerno zaviralno aktivnost na holinesteraze, medtem ko pri GST ni bilo inhibicije. Pri encimih živalskega izvora smo anti-AChE aktivnost določili pri 3 kompleksih, anti-BChE aktivnost pa pri 12 spojinah. Anti-AChE aktivnost na encimu humanega izvora smo testirali na 3 spojinah in potrdili pri 2 spojinah. Naša študija je odprla nov vpogled za nadaljnja testiranja rutenijevih kompleksov kot potencialnih večtarčnih zdravil in kot novo terapijo za zdravljenje tumorjev in nevrodegenerativnih obolenj.
Ključne besede
rutenijeve spojine;encimski inhibitorji;holinesteraze;glutation S-transferaza;inhibicija;Alzheimerjeva bolezen;
Podatki
Jezik: |
Slovenski jezik |
Leto izida: |
2019 |
Tipologija: |
2.09 - Magistrsko delo |
Organizacija: |
UL BF - Biotehniška fakulteta |
Založnik: |
[S. Ristovski] |
UDK: |
577.2(043.2) |
COBISS: |
5214287
|
Št. ogledov: |
563 |
Št. prenosov: |
145 |
Ocena: |
0 (0 glasov) |
Metapodatki: |
|
Ostali podatki
Sekundarni jezik: |
Angleški jezik |
Sekundarni naslov: |
Evaluation of selected ruthenium complexes as potential cholinesterases and glutathione-S-transferase inhibitors |
Sekundarni povzetek: |
Discovery of antitumor activity of cisplatin and its analogues, as well as their successful medical application in the treatment of a plethora of tumours and symptomatic treatment of Alzheimer disease (AD), revived interest in research and development of new platinum- and other metal-based drugs, e.g. ruthenium. Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) has beneficial impact on AD patients. The result is increased concentration of acetylcholine in the synaptic cleft, which leads to improvement of cognitive functions. Glutathione S-transferase (GST) has increased expression in cancer cells; thus, GST inhibitors represent potential antitumor agents. In previous studies, ruthenium complexes have shown good anti-AChE, anti-BChE and anti-GST activity and as such possible therapeutic applications in the treatment of AD and cancer, where they act as multi-target drugs. Hence, we have tested 34 newly synthesized ruthenium complexes, their precursors and ligands on enzymes from animal and human origin. Results of this study have shown, that our newly synthesised ruthenium complexes have low or moderate inhibitory activity on the cholinesterases, whilst they lack GST inhibition. Anti-AChE activity is shown in 3 complexes and anti-BChE activity in 12 complexes when enzymes of animal origin are used. Anti-AChE activity of the enzyme of human origin was tested on 3 and shown in 2 compounds. Our study has opened new insight for further testing of ruthenium complexes as potential multi-target drugs and for novel therapy to treat tumours and neurodegenerative diseases. |
Sekundarne ključne besede: |
Ruthenium compounds;enzyme inhibitors;cholinesterases;glutathione S transferase;inhibition;Alzheimerʼs disease; |
Vrsta dela (COBISS): |
Magistrsko delo/naloga |
Študijski program: |
0 |
Konec prepovedi (OpenAIRE): |
1970-01-01 |
Komentar na gradivo: |
Univ. Ljubljana, Biotehniška fak. |
Strani: |
IX, 50, [1] f. |
ID: |
11223573 |