No public access
master's thesis
Effect of chosen ruthenium compounds on glutathione S-transferase and cholinesterase enzymes activity

Monika Uzelac (2016)
University of Rijeka
Department of Biotechnology
Metadata
TitleUtjecaj odabranih rutenijevih spojeva na aktivnost glutation S-transferaze i enzima iz skupine kolinesteraza
AuthorMonika Uzelac
Mentor(s)Kristina Sepčić (thesis advisor)
Iztok Turel (thesis advisor)
Abstract
Acetilkolinesteraza (AChE) i butirilkolinesteraza (BChE) su enzimi iz skupine kolinesteraza čija inhibicija može imati pozitivne učinke u liječenju Alzheimerove bolesti. Inhibicijom AChE i BChE povećava se koncentracija neurotransmitera acetilkolina u sinaptičkim pukotinama što dovodi do poboljšanja kognitivnih funkcija pacijenata. Stoga ne začuđuje činjenica da su oba enzima terapeutski zanimljive mete za ublažavanje simptoma Alzheimerove bolesti. Glutation S-transferaza (GST) je enzim čija je ekspresija povećana u stanicama raka, te inhibitori GST predstavljaju potencijalna protutomorska sredstva. U zadnje vrijeme, rutenijevi spojevi se dosta istražuju radi obećavajuće antitumorske i antimetastatske sposobnosti. Rutenijevi su kompleksi u prijašnjim istraživanjima pokazali anti-AChE aktivnost i anti-GST aktivnost te moguću terapijsku primjenu u liječenju Alzheimerove bolesti i raka, pri čemu mogu djelovati kao višeciljni lijekovi. Stoga smo u okviru diplome testirali niz novo sintetiziranih rutenijevih spojeva i njihovih prekurzora na inhibiciju gore spomenutih enzima. Rezultati našeg istraživanja pokazali su da rutenijevi spojevi imaju dobru inhibitornu aktivnost na spomenute enzime, štoviše, neki od njih djeluju inhibitorno na sva 3 enzima što ih čini potencijalnim višeciljnim lijekovima. Dobru anti-AChE aktivnost je pokazalo čak 15 spojeva, anti-BChE aktivnost je imalo 14 spojeva, te anti-GST aktivnost su imala 4 spoja. Vrijedi spomenuti spoj JKZU13-08 koji je djelovao inhibitorno na sva 3 enzima. S ovim istraživanjem se otvorila mogućnost za daljnja ispitivanja rutenijevih spojeva kao mogućih lijekova.
Keywordsruthenium complexes acetylcholinesterase butyrylcholinesterase glutathione S-transferase Alzheimer's disease enzyme inhibitors.
Parallel title (English)Effect of chosen ruthenium compounds on glutathione S-transferase and cholinesterase enzymes activity
Committee MembersKristina Sepčić (committee chairperson)
Iztok Turel (committee member)
Sandra Kraljević Pavelić (committee member)
Nataša Poklar Ulrih (committee member)
GranterUniversity of Rijeka
Lower level organizational unitsDepartment of Biotechnology
PlaceRijeka
StateCroatia
Scientific field, discipline, subdisciplineBIOTECHNICAL SCIENCES
Biotechnology
Study programme typeuniversity
Study levelgraduate
Study programmeDrug research and development
Academic title abbreviationmag. pharm. inv.
Genremaster's thesis
Language Croatian
Defense date2016-09-22
Parallel abstract (English)
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes from the group of cholinesterases whose inhibition may have beneficial effects in the treatment of Alzheimer's disease. Inhibition of AChE and BChE increases the concentration of the neurotransmitter acetylcholine in the synaptic cleft which leads to the improvement of cognitive functions in patients. It is therefore not surprising that both enzymes are therapeutically interesting targets for alleviating the symptoms of Alzheimer’s disease. Glutathione S-transferase (GST) is an enzyme whose expression is increased in cancer cells, and inhibitors of GST represent potential antitumor agents. In the last years, ruthenium compounds have been investigated for their promising antitumor and antimetastatic capabilities. In previous studies, ruthenium complexes have shown good anti-AChE activity and anti-GST activity and possible therapeutic applications in the treatment of Alzheimer’s disease and cancer, where they can act as multitarget drugs. Therefore, we have tested 32 newly synthesized ruthenium complexes and their precursors for inhibition of the above mentioned enzymes. Results of this study have shown that ruthenium complexes have good inhibitory activity on enzymes, moreover some of the complexes have inhibited all of the three tested enzymes, which makes them potential multitarget drugs. Good anti-AChE activity is shown in 15 complexes, anti-BChE activity in 14 complexes, and anti-GST activity in 4 of the complexes. Complex worth mentioning is JKZU13-08 which exhibited strong inhibitory activity on all of the three tested enzymes. This study has opened the possibility for further testing of ruthenium complexes as potential drugs.
Parallel keywords (Croatian)rutenijevi spojevi acetilkolinesteraza butirilkolinesteraza glutation S-transferaza Alzheimerova bolest enzimski inhibitori.
Resource typetext
Access conditionNo public access
URN:NBNhttps://urn.nsk.hr/urn:nbn:hr:193:404888
CommitterLea Lazzarich