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master's thesis
Sinteza i karakterizacija harmicina; novih 1,2,3- triazolskih derivata harmina i cimetne kiseline
Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry, 2020. urn:nbn:hr:163:638674
Konjevod, Vedrana
University of Zagreb
Faculty of Pharmacy and Biochemistry
Department of medicinal chemistry

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

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Konjevod, V. (2020). Sinteza i karakterizacija harmicina; novih 1,2,3- triazolskih derivata harmina i cimetne kiseline (Master's thesis). Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry. Retrieved from https://urn.nsk.hr/urn:nbn:hr:163:638674

Konjevod, Vedrana. "Sinteza i karakterizacija harmicina; novih 1,2,3- triazolskih derivata harmina i cimetne kiseline." Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2020. https://urn.nsk.hr/urn:nbn:hr:163:638674

Konjevod, Vedrana. "Sinteza i karakterizacija harmicina; novih 1,2,3- triazolskih derivata harmina i cimetne kiseline." Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, 2020. https://urn.nsk.hr/urn:nbn:hr:163:638674

Konjevod, V. (2020). 'Sinteza i karakterizacija harmicina; novih 1,2,3- triazolskih derivata harmina i cimetne kiseline', Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, accessed 29 December 2024, https://urn.nsk.hr/urn:nbn:hr:163:638674

Konjevod V. Sinteza i karakterizacija harmicina; novih 1,2,3- triazolskih derivata harmina i cimetne kiseline [Master's thesis]. Zagreb: University of Zagreb, Faculty of Pharmacy and Biochemistry; 2020 [cited 2024 December 29] Available at: https://urn.nsk.hr/urn:nbn:hr:163:638674

V. Konjevod, "Sinteza i karakterizacija harmicina; novih 1,2,3- triazolskih derivata harmina i cimetne kiseline", Master's thesis, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, 2020. Available at: https://urn.nsk.hr/urn:nbn:hr:163:638674

Metadata
TitleSinteza i karakterizacija harmicina; novih 1,2,3- triazolskih derivata harmina i cimetne kiseline
Title (english)Synthesis and characterization of harmicines; novel 1,2,3- triazole derivatives of harmine and cinnamic acid
AuthorVedrana Konjevod
MentorIvana Perković (mentor)
Committee memberIvana Perković (predsjednik povjerenstva)
Committee memberZrinka Rajić (član povjerenstva)
Committee memberMirela Matić (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Pharmacy and Biochemistry
(Department of medicinal chemistry)
Zagreb
Defense date and country2020-07-14, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Pharmacy
Pharmacy
Abstract
Cilj ovog rada bila je sinteza i karakterizacija četiriju novih harmicina, hibridnih spojeva koji preko triazolske poveznice vežu dva farmakofora s antimalarijskim učinkom u jednu molekulu; β-karboline harmin ili harmol te derivate cimetne kiseline (CAD). Za sintezu ciljanih spojeva odabran je prikazani reakcijski put koji je uključio prevođenje derivata cimetne kiseline u azide (5a,b), dok su harmin i harmol u reakcijama N- i O-propargiliranja iskorišteni za dobivanje redom N i O-alkina (1,2). Terminalni alkini 1 i 2 s azidima dobivenim iz derivata cimetne kiseline (5a,b) u reakciji Huisgenove cikloadicije katalizirane bakrom (I) dali su konačne produkte, 1,2,3-triazolske derivate harmina i cimetne kiseline (6a,b i 7a,b). Svim novosintetiziranim spojevima struktura je potvrđena uobičajenim analitičkim i spektroskopskim metodama (IR, 1H i 13C NMR, MS) te im je određena temperatura tališta. Za konačne produkte (6a,b i 7a,b) je temeljem izračuna molekulskih deskriptora napravljena računalna predikcija njihovih farmakokinetičkih svojstava., najvažnije od kojih je oralna bioraspoloživost. U daljnjim ispitivanjima, koja prelaze okvir ovog rada, sintetiziranim derivatima je ispitano antimalarijsko i citotoksično djelovanje.
Abstract (english)
The aim of this thesis was synthesis and characterization of four new harmicines, hybrides which through triazole spacer comprise two pharmacophores with antimalarial activity into single molecule; i.e. β-carboline harmine or harmol and cinnamic acid derivatives (CAD). The shown reaction pathway chosen for the synthesis of final compounds has included obtaining azides 5a,b from cinnamic acid derivatives in several steps, while harmine and harmol have generated N- and O-alkynes (1,2) in the reactions of N- and O-propargylations. Cu(I) catalyzed organic azide-terminal alkyne cycloaddition was employed for preparation of final 1,2,3-triazole N- (6a,b) and O- derivatives (7a,b) of harmine and cinnamic acid from above mentioned reactants. The structures of the newly synthesized compounds were confirmed using conventional analytical and spectroscopic methods (IR, 1H i 13C NMR, MS). Besides, the melting points of solid compounds were determined. Computer models have been fostered for the prediction of pharmacokinetical properties of the final compounds (6a,b i 7a,b), most important property being oral bioavailability. Subsequent studies, that have surpassed this thesis, had also investigated antimalarial and citotoxic activity of the final compounds.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:163:638674
Study programmeTitle: Pharmacy
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2021-04-29 09:10:56