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master's thesis
Priprava kvaternih O-benzil-oksima kinuklidina te njihova antikolinesterazna aktivnost
Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry, 2024. urn:nbn:hr:163:508258
Zajec, Ivan
University of Zagreb
Faculty of Pharmacy and Biochemistry
Department of organic chemistry

Institutional repository: Repository of Faculty of Pharmacy and Biochemistry University of Zagreb

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Zajec, I. (2024). Priprava kvaternih O-benzil-oksima kinuklidina te njihova antikolinesterazna aktivnost (Master's thesis). Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry. Retrieved from https://urn.nsk.hr/urn:nbn:hr:163:508258

Zajec, Ivan. "Priprava kvaternih O-benzil-oksima kinuklidina te njihova antikolinesterazna aktivnost." Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2024. https://urn.nsk.hr/urn:nbn:hr:163:508258

Zajec, Ivan. "Priprava kvaternih O-benzil-oksima kinuklidina te njihova antikolinesterazna aktivnost." Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2024. https://urn.nsk.hr/urn:nbn:hr:163:508258

Zajec, I. (2024). 'Priprava kvaternih O-benzil-oksima kinuklidina te njihova antikolinesterazna aktivnost', Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, accessed 23 November 2024, https://urn.nsk.hr/urn:nbn:hr:163:508258

Zajec I. Priprava kvaternih O-benzil-oksima kinuklidina te njihova antikolinesterazna aktivnost [Master's thesis]. Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry; 2024 [cited 2024 November 23] Available at: https://urn.nsk.hr/urn:nbn:hr:163:508258

I. Zajec, "Priprava kvaternih O-benzil-oksima kinuklidina te njihova antikolinesterazna aktivnost", Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, 2024. Available at: https://urn.nsk.hr/urn:nbn:hr:163:508258

Metadata
TitlePriprava kvaternih O-benzil-oksima kinuklidina te njihova antikolinesterazna aktivnost
Title (english)Synthesis of O-benzyl oxime quinuclidines and their anticholinesterase activity
AuthorIvan Zajec
MentorBernard Denegri (mentor)
MentorInes Primožič (mentor)
Committee memberBernard Denegri (predsjednik povjerenstva)
Committee memberInes Primožič (član povjerenstva)
Committee memberAna Budimir (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Pharmacy and Biochemistry
(Department of organic chemistry)
Zagreb
Defense date and country2024-07-23, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Pharmacy
Pharmacy
Abstract
U okviru ovog rada klasičnim postupcima organske sinteze pripravljen je O-benzilni eter kinuklidin- 3-on oksima reakcijom hidroklorida kinuklidin-3-ona i O-benzilhidroksilamina, bez dodatka anorganskih ili organskih baza. Kvaternizacijom kinuklidinskog atoma dušika u molekuli pripravljenog O-benziloksima s nesupstituiranim i odabranim, različito supstituiranim benzilbromidima (trifluormetilna ili trifluormetoksi skupina u para položaju, tert-butilna skupina u para ili meta položajima, spojevi halogena na određenim pozicijama prstena) pripravljen je niz od devet spojeva, od kojih osam do sada nisu opisani u literaturi. Novosintetiziranim spojevima određeno je talište te je struktura određena i potvrđena spektroskopskim metodama: infracrvenom spektroskopijom, 1D nuklearnom magnetskom rezonancijom te spektrometrijom masa. Nakon sinteze te fizikalno-kemijske karakterizacije spojeva, svima je određen inhibitorni potencijal prema enzimu butirilkolinesterazi iz konjskog seruma (EC 3.1.1.8) korištenjem Ellmanove kolorimetrijske metode za određivanje aktivnosti acetilkolinesteraze. Svi ispitani spojevi reverzibilno su inhibirali enzim u mikro- i nanomolarnom području. Kao najsnažniji inhibitor pokazao se spoj 6, kvaterni derivat oksima s dvije tert-butilne skupine u meta položajima na aromatskom prstenu benzilne skupine vezane na kvaterni dušikov atom kinuklidina (IC50 = 0,28 ± 0,01 μmol dm-3).
Abstract (english)
Within this work, O-benzyl ether quinuclidin-3-one oxime was prepared by the reaction of hydrochloride salts of quinuclidin-3-one and O-benzylhydroxylamine, without the addition of inorganic or organic bases. By quaternization of a quinuclidine nitrogen atom in a molecule prepared with O-benzyl oxime with unsubstituted and selected, differently substituted benzyl bromides (trifluoromethyl or trifluoromethoxy groups in the para- position, tert-butyl group in the para or meta positions, halogen compounds at certain benzene ring positions), a series of nine compounds, quaternary derivatives of quinuclidine, was prepared. Out of those nine, eight have not been described in the literature so far. The melting point of the newly synthesized compounds was determined, and the structure was characterized and confirmed by spectroscopic methods: infrared spectroscopy, 1D nuclear magnetic resonance and mass spectrometry. Subsequent to physicochemical characterization of the compounds, the inhibitory potential toward the enzyme butyrylcholinesterase from equine serum (EC 3.1.1.8) was determined using the Ellman colorimetric method to determine cholinesterase activity. All tested compounds reversibly inhibited the enzyme in the micromolar and nanomolar range. The most potent inhibitor was quaternary O-benzyl oxime derivative with two tert-butyl groups in meta positions on the quaternary benzyl group (IC50 = 0.28 ± 0.01 μmol dm-3).
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:163:508258
Study programmeTitle: Pharmacy - integrated undergraduate and graduate - university study
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: sveučilišni magistar farmacije (sveučilišni magistar farmacije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2024-10-10 11:29:17