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master's thesis
Novi derivati citozina: sinteza "klik" reakcijom, strukturna karakterizacija, in silico analiza i antitumorska ispitivanja
Zagreb: University of Zagreb, Faculty of Chemical Engineering and Technology, 2015. urn:nbn:hr:149:883700
Mihovilović, Moris
University of Zagreb
Faculty of Chemical Engineering and Technology

Institutional repository: Repository of Faculty of Chemical Engineering and Technology University of Zagreb

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Mihovilović, M. (2015). Novi derivati citozina: sinteza "klik" reakcijom, strukturna karakterizacija, in silico analiza i antitumorska ispitivanja (Master's thesis). Zagreb: University of Zagreb, Faculty of Chemical Engineering and Technology. Retrieved from https://urn.nsk.hr/urn:nbn:hr:149:883700

Mihovilović, Moris. "Novi derivati citozina: sinteza "klik" reakcijom, strukturna karakterizacija, in silico analiza i antitumorska ispitivanja." Master's thesis, University of Zagreb, Faculty of Chemical Engineering and Technology, 2015. https://urn.nsk.hr/urn:nbn:hr:149:883700

Mihovilović, Moris. "Novi derivati citozina: sinteza "klik" reakcijom, strukturna karakterizacija, in silico analiza i antitumorska ispitivanja." Master's thesis, University of Zagreb, Faculty of Chemical Engineering and Technology, 2015. https://urn.nsk.hr/urn:nbn:hr:149:883700

Mihovilović, M. (2015). 'Novi derivati citozina: sinteza "klik" reakcijom, strukturna karakterizacija, in silico analiza i antitumorska ispitivanja', Master's thesis, University of Zagreb, Faculty of Chemical Engineering and Technology, accessed 26 November 2024, https://urn.nsk.hr/urn:nbn:hr:149:883700

Mihovilović M. Novi derivati citozina: sinteza "klik" reakcijom, strukturna karakterizacija, in silico analiza i antitumorska ispitivanja [Master's thesis]. Zagreb: University of Zagreb, Faculty of Chemical Engineering and Technology; 2015 [cited 2024 November 26] Available at: https://urn.nsk.hr/urn:nbn:hr:149:883700

M. Mihovilović, "Novi derivati citozina: sinteza "klik" reakcijom, strukturna karakterizacija, in silico analiza i antitumorska ispitivanja", Master's thesis, University of Zagreb, Faculty of Chemical Engineering and Technology, Zagreb, 2015. Available at: https://urn.nsk.hr/urn:nbn:hr:149:883700

Metadata
TitleNovi derivati citozina: sinteza "klik" reakcijom, strukturna karakterizacija, in silico analiza i antitumorska ispitivanja
Title (english)The novel cytosine derivatives: synthesis by "click" reaction, structural characterization, in silico analysis and antitumor evaluations
AuthorMoris Mihovilović
MentorTatjana Gazivoda Kraljević (mentor)
Committee memberTatjana Gazivoda Kraljević (predsjednik povjerenstva)
Committee memberMaja Stipković Babić (član povjerenstva)
Committee memberSvjetlana Krištafor (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Chemical Engineering and Technology
Zagreb
Defense date and country2015-07-08, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Organic Chemistry
Abstract
Cilj ovog istraživanja bio je pripraviti derivate N-4-benzoilcitozinas 1,2,3-triazolnim supstituentima u položajima N-1 i N-3 radi njihovih citostatskih ispitivanja in vitro na staničnim linijama zloćudnih tumorskih linija porijeklom iz čovjeka: HeLa (adenokarcinom vrata maternice), CaCo-2 (adenokarcinom debelog crijeva), Raji (Burkittov limfom) i K562 (kronična mijeloidna leukemija u blastičnoj krizi). N-1 propargilirani i N,N-1,3-dipropargilirani derivati N-4-benzoilcitozina (2, 4 i 5) pripravljeni su reakcijom alkiliranja N-4-benzoil-5-jodcitozina ili N-4-benzoilcitozina s propargil-bromidom uz K2CO3 kao bazu. Huisgenovom 1,3-dipolarnom cikloadicijom potpomognutom mikrovalovima N,N-1,3-dipropargiliranog derivata N-4-benzoil-citozina (5) s odgovarajućim azidima uz katalizator sintetizirani su N,N-1,3-ditriazolilni derivati citozina (6-12). Oksidacijom propargilnog supstituenta na položaju N-3 citozinskog prstena dobiveni su N-3-(2-oksopropil)-N-1-triazolilni derivati (13-20) kao nusprodukti. Strukturna karakterizacija novopripravljenih spojeva provedena je 1H i 13C NMR spektroskopijom i masenom spektrometrijom, a moguće biološke mete i farmakološka djelovanja novopripravljenih spojeva predviđene su in silico analizom. Od svih analiziranih spojeva najbolje predviđene biološke aktivnosti imaju N,N-1,3-dipropargilirani N-4-benzoil-5-jodcitozin (2), derivat N-4-benzoil-ditriazolilcitozina koji na 1,2,3-triazolnom prstenu u položaju 1 ima p-trifluormetilfenilni supstituent (6) i derivat N-4-benzoil-N-3-(2-oksopropil)-N-1-triazolilcitozina koji na 1,2,3-triazolnom prstenu u položaju 1 ima benzilni supstituent (17).
Abstract (english)
The aim of this research was to synthesize N-4-benzoyl-cytosine derivatives with 1,2,3-triazole substituents on N-1 and N-3 in order to perform cytostatic evaluations in vitro against malignant human tumor cell lines: HeLa (cervical adenocarcinoma), CaCo-2 (colon adenocarcinoma), Raji (Burkitt lymphoma) i K562 (chronic myeloid leukemia in blast crisis). N-1 propargylated and N,N-1,3-dipropargylated N-4-benzoylcytosine derivatives (2, 4 i 5) were prepared by alkylation of N-4-benzoy-5-iodocytosine or N-4-benzoylcytosine with propargyl-bromide and K2CO3 as the base. The microwave assisted Huisgen 1,3-bipolar cycloaddition of the N,N-1,3-dipropargylated N-4-benzoylcytosine derivative (5) with the corresponding azides and catalyst gave N,N-1,3-ditriazole cytosine derivatives (6-12). Byproducts of this reaction, N-3-(2-oxopropyl)-N-1-triazole derivatives (13-20) were obtained by oxidation of the N-3 propargyl substituent. Structural characterization of the newly synthesized compounds was performed by 1H i 13C NMR spectroscopy and mass spectrometry, and the possible biological targets and pharmacological activity of the prepared molecules were predicted by in silico analysis. Of all the analysed compounds, the best results show N,N-1,3-dipropargylated N-4-benzoyl-5-iodocytosine (2), N-4-benzoyl-ditriazolecytosine derivative with a p-trifluoromethylphenyl supstituent on the 1,2,3-triazole ring (6) and N-4- benzoyl -N-3-(2-oxopropyl)-N-1-triazolecytosine derivative with a benzyl supstituent on the 1,2,3-triazole ring (17).
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:149:883700
Study programmeTitle: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry
Course: Applied organic chemistry
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2016-12-07 13:10:02