No public access
master's thesis
Anticholinesterase activity of the synthetic derivatives of barettin

Marija Cergolj (2016)
University of Rijeka
Department of Biotechnology
Metadata
TitleAntikolinesterazna aktivnost sintetskih derivata baretina
AuthorMarija Cergolj
Mentor(s)Kristina Sepčić (thesis advisor)
Abstract
Budući da su sesilni morski organizmi, osobito morske spužve, bogat izvor mikroorganizama i bioaktivnih prirodnih spojeva, oni predstavljaju temelj za razvoj potencijalnih lijekova. Inhibitori enzima acetilkolinesteraze, koji imaju širu primjenu u medicini, upravo su jedni od tih lijekova. S obzirom na to da nijedan inhibitor acetilkolinesteraze iz morskog svijeta nije komercijalni proizvod, prikupljanje i analiza morskih organizama vrijedan je pokušaj da se istraže novi prirodni spojevi te njihova potencijalna upotreba u liječenju. Iz farmakološki zanimljivih morskih prirodnih spojeva izoliranih iz spužve Geodia barretti koji su prethodno pokazali sposobnost inhibicije acetilkolinesteraze stvoren je set semisintetskih analoga (spojevi MBC) kako bi se istražilo njihovo farmakološko djelovanje. U istu je svrhu stvoren i set spojeva Kine, analoga bromocionina izoliranog iz morske ascidije Ciona edwardsii. Testirani analozi pokazali su antiacetilkolinesteraznu aktivnost. Analizom Dixonovih dijagrama utvrdilo se da je riječ o reverzibilnim kompetetivnim inhibitorima. Nijedan od analoga nije pokazao inhibitornu snagu kakvu imaju prirodni spojevi baretin i 8,9-dihidrobaretin. Najaktivniji analozi MBC-197 te Kine22 dalje su se testirali na živčano-mišićnom preparatu. Pokazalo se da nijedan od njih u testiranim koncentracijama ne utječe na neuromuskularni spoj ni na membranske potencijale.
Keywordsacetylcholinesterase Geodia barretti acetylcholineesterase inhibitors secondary metabolites Alzheimer’s disease
Parallel title (English)Anticholinesterase activity of the synthetic derivatives of barettin
Committee MembersSandra Kraljević Pavelić (committee chairperson)
Robert Frangež (committee member)
Kristina Sepčić (committee member)
Monika Cecilija Žužek (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 date2016-05-18
Parallel abstract (English)
Sessile marine organisms, especially marine sponges, represent an important basis for potential development of certain drugs since they are rich in microorganisms and bioactive natural products. Such an example are inhibitors of acetylcholinesterase, which are already widely used for medical purposes. None of the acetylcholinesterase inhibitors from the marine realm are yet commercial products, therefore collecting and analysing marine organisms represent a valuable effort to further discover new natural products and their potential medical use. In order to investigate their pharmacological effects, a set of semisynthetic analogs (MBC) was designed out of the marine natural products isolated from the sponge Geodia barretti. These natural compounds had previously shown inhibitory activity towards acetylcholinesterase. Another set of analogs (Kine) was designed out of bromocyonine isolated from the Mediterranean ascidian Ciona edwardsii. Tested analogs have shown acetylcholinesterase-inhibitory activity. Analyses of Dixon plots have revealed these compounds as reversible competitive inhibitors. None of the semisynthetic compounds were as active as isolated compounds barettin and 8,9-dihydrobarettin. The most active analogs MBC-197 and Kine22 underwent further testing on neuromuscular preparation. In tested concentrations, none of them exerted an action on neuromuscular transmission nor affected membrane potentials.
Parallel keywords (Croatian)acetilkolinesteraza Geodia barretti inhibitori acetilkolinesteraze sekundarni metaboliti Alzheimerova bolest
Resource typetext
Access conditionNo public access
URN:NBNhttps://urn.nsk.hr/urn:nbn:hr:193:300619
CommitterIvana Dorotić