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Sinteza in biološka aktivnost rutenijevih koordinacijskih spojin z izbranimi O,O-, N,O- in N,N-veznimi ligandi
Gričar, Simona (Author), Turel, Iztok (Mentor) More about this mentor... This link opens in a new window

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Abstract
Bioanorganska kemija se ukvarja s sintezo koordinacijskih spojin z biološko aktivnostjo. Primer takšne spojine je cisplatin, ki se že od 70. let prejšnjega stoletja uporablja kot kemoterapevtik za zdravljenje rakavih obolenj. V želji po boljši učinkovitosti in manjšem številu stranskih učinkov se po svetu raziskujejo nove koordinacijske spojine kovin prehoda s protitumorsko aktivnostjo, kar je bil tudi namen mojega magistrskega dela. Sintetizirala sem nove rutenijeve(II) komplekse z β-diketoni kot O,O-veznimi ligandi, 8-hidroksikinolini kot N,O-veznimi ligandi in derivati pirazolilpiridina kot N,N-veznimi ligandi. Sintetizirane spojine sem okarakterizirala z metodami spektroskopije NMR, masne spektrometrije, infrardeče in UV-Vis spektroskopije ter elementne analize CHN. Pridobila sem tudi kristale treh kompleksov za rentgensko strukturno analizo. Da bi ovrednotila biološko aktivnost izbranih kompleksov, sem opravila teste citotoksičnosti z MTT na treh celičnih linijah raka na želodcu, kjer je ena izmed spojin dosegla vrednost IC50 = 0,8 μM. Metoda prenosa Western je pokazala, da spojini z najboljšo citotoksičnostjo sprožita stres endoplazemskega retikuluma ter na ta način omejujeta rast in razmnoževanje rakavih celic. Ključne

Language:Slovenian
Keywords:rutenijevi(II) kompleksi, dvovezni ligandi, protitumorska aktivnost
Work type:Master's thesis/paper (mb22)
Tipology:2.09 - Master's Thesis
Organization:FKKT - Faculty of Chemistry and Chemical Technology
Year:2019
COBISS.SI-ID:1538322883 Link is opened in a new window
Views:151
Downloads:53
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Secondary language

Language:English
Title:Synthesis and biological activity of ruthenium coordination compounds with selected O,O-, N,O- and N,N-binding ligands
Abstract:
One of the main topics of bioinorganic chemistry is the synthesis of coordination compounds with biological activity. An example of such compounds is cisplatin, which has been used as a chemotherapeutic drug in cancer treatments since the 1970s. In order to acquire better efficacy and smaller levels of side effects, research groups worldwide are focusing on coordination compounds of transition metals as new potential drugs, which was the field of research for my Master thesis. I have synthesized new ruthenium(II) complexes with β-diketones as O,O-binding ligands, 8-hydroxyquinolines as N,O-binding ligands and pyrazolylpyridine derivates as N,N-binding ligands. The synthesized compounds were characterized with NMR spectroscopy, mass spectrometry, infrared and UV-Vis spectroscopy, and elemental analysis. Crystals of three complexes were analysed with X-rays. With an aim to evaluate biological activity of nine selected complexes, MTT cytotoxicity assays was performed on three different gastric cancer cell lines, where one of the complexes reached IC50 as low as 0,8 μM. Furthermore, the results of Western blot technique showed that the two compounds with the best cytotoxicity have an impact on the ER-stress pathway, and can in that way limit cancer cells growth and proliferation.

Keywords:ruthenium(II) complexes, bidentate ligands, anticancer activity

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