O-benziloksimi kao inhibitori butirilkolinesteraze

master's thesis

• Title (english): O-benzyloximes as butyrylcholinesterase inhibitors
• Author: Matea Laučan
• Mentor: Ines Primožič (mentor)
• Mentor: Alma Ramić (komentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Biserka Prugovečki (član povjerenstva)
• Committee member: Adriana Kenđel (član povjerenstva)
• Committee member: Nikola Cindro (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2023-09-18, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U okviru ovog rada klasičnim postupcima organske sinteze pripremljen je O-benzilni eter kinuklidin-3-
on-oksima reakcijom hidroklorida kinuklidin-3-ona i O-benzilhidroksilamina bez dodatka organskih ili
anorganskih baza. Kvaternizacijom kinuklidinskog atoma dušika u molekuli sintetiziranog Obenziloksima s metil-jodidom te odabranim, različito supstituiranim benzil-bromidima (metilna ili nitroskupina te atomi halogena u meta ili para položaju) pripremljena je serija od dvanaest novih kvaternih
derivata. Odabrani spojevi imaju različite modifikacije u strukturi kako bi se mogli definirati strukturni
parametri važni za postizanje poboljšane biološke aktivnosti spojeva u interakciji s kolinesterazama.
Pripremljenim spojevima određeno je talište te je struktura potvrđena infracrvenom spektroskopijom,
spektrometrijom masa te 1D i 2D spektroskopijom nuklearne magnetske rezonancije. Nadalje, svim
pripremljenim spojevima određen je inhibitorni potencijal prema enzimu butirilkolinesterazi iz konjskog
seruma (EC 3.1.1.8) korištenjem Ellmanove metode za kolorimetrijsko određivanje aktivnosti
kolinesteraze.

Abstract (english)

In this work, O-benzyl ether of quinuclidin-3-one oxime was prepared by the reaction of
hydrochloride salts of quinuclidin-3-one and O-benzylhydroxylamine without the addition of
organic or inorganic bases. A series of twelve new quaternary derivatives were prepared by
quaternization of the quinuclidine nitrogen atom with methyl iodide and selected, differently
substituted benzyl bromides (methyl or nitro group and halogen atoms in the meta or para
position). The selected compounds have different modifications in the structure to define the
structural parameters important for achieving improved biological activity in the interaction
with cholinesterases. The melting points of the prepared compounds were determined, and the
structure was confirmed by infrared spectroscopy, mass spectrometry and 1D and 2D nuclear
magnetic resonance spectroscopy. Furthermore, the inhibitory potential of all prepared
compounds toward the enzyme butyrylcholinesterase from horse serum (EC 3.1.1.8) was
determined using the Ellman method for colorimetric determination of cholinesterase activity.

• Keywords: kinuklidin-3-on-O-benziloksim; kvaterni derivati; butirilkolinesteraza; inhibicija enzima
• Keywords (english): quinuclidin-3-one-O-benzyloxime; quaternary derivatives; butyrylcholinesterase; enzyme inhibition
• Language: croatian
• URN:NBN: urn:nbn:hr:217:020612
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-09-18
• Created on: 2023-09-25 12:57:23