O-tert-butiloksimi kinuklidina kao inhibitori butirilkolinesteraze

master's thesis

• Title (english): Quinuclidine O-tert-butyl oximes as cholinesterase inhibitors
• Author: Dora Perić
• Mentor: Ines Primožič (mentor)
• Committee member: Ines Primožič (predsjednik povjerenstva)
• Committee member: Jana Pisk (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: 2024-09-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U okviru ovoga rada pripravljen je O-tert-butilni eter kinuklidin-3-on-oksima reakcijom hidroklorida O-tert-butilhidroksilamina i kinuklidin-3-ona klasičnom organskom sintezom bez korištenja baze. Kvaternizacijom tercijarnoga dušikovog atoma kinuklidina metil-jodidom te različito supstituiranim benzil-bromidima (metilna ili nitro skupina te atomi halogena u meta ili para položaju) pripravljena je serija od dvanaest novih N-kvaternih derivata O-tert-butilnog etera kinuklidin-3-on-oksima. Struktura pripravljenih spojeva potvrđena je standardnim analitičkim postupcima koji uključuju infracrvenu spektroskopiju, 1D (1H, 13C) i 2D spektroskopske metode NMR te spektrometriju masa. Svim pripravljenim spojevima određen je inhibitorni potencijal prema enzimu butirilkolinesterazi (EC 3.1.1.8) iz konjskog seruma korištenjem Ellmanove metode za kolorimetrijsko određivanje aktivnosti acetilkolinesteraze.

Abstract (english)

In this work, O-tert-butyl ether of quinuclidin-3-one-oxime was prepared by the reaction of O- tert-butylhydroxylamine and quinuclidin-3-one hydrochloride by classic organic synthesis without using a base. By quaternization of the tertiary nitrogen atom of quinuclidine with methyl iodide and differently substituted benzyl bromides (methyl or nitro group and halogen atoms in the meta or para position), a series of twelve new N-quaternary derivatives of O-tert- butyl ether quinuclidin-3-one-oxime was prepared. The structure of the prepared compounds was confirmed by standard analytical procedures that include infrared spectroscopy, 1D (1H,13C) and 2D NMR spectroscopic methods and mass spectrometry. The inhibitory potential of all prepared compounds to the enzyme butyrylcholinesterase (EC 3.1.1.8) from horse serum was determined using the Ellman method for colorimetric determination of cholinesterase activity.

• Keywords: butirilkolinesteraza; inhibicija; kvaterni derivati; O-tert-butiloksim kinuklidina
• Keywords (english): butyrylcholinesterase; inhibition; O-tert-butyloxime of quinuclidine; quaternary derivatives
• Language: croatian
• URN:NBN: urn:nbn:hr:217:646405
• Project: Number: IP-2022-10-9525; Title: Metom usmjerena sinteza inhibitora kolinesteraza podržana strojnim učenjem; Title: Target-guided synthesis of cholinesterase inhibitors supported by machine learning; Acronym: TargetCh; Leader: Ines Primožič; Jurisdiction: Croatia; Funder: Hrvatska zaklada za znanost; Funding stream: Research Projects
• Study programme: Title: Graduate university studies in chemistry; specializations in: Graduate university studies in chemistry; Course: Graduate university studies in chemistry; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra kemije (sveučilišni/a magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-10-14 12:50:56