@phdthesis{
author = "Vilipić, Jovana",
year = "2017",
abstract = "U okviru ove doktorske disertacije je sintetisana serija aminokiselinskihderivata seskviterpenskog hinona avarona, izolovanog iz morskog sunđera Dysideaavara, kao i model jedinjenja tert-butilhinona.Određena je in vitro antitumorska aktivnost svih jedinjenja prema humanimtumorskim ćelijskim linijama (HeLa, A549, Fem-X, K562, MDA-MB-453) i zdravojMRC-5 ćelijskoj liniji. Utvrđeno je da aminokiselinski derivati avarona pokazuju jačedejstvo nego odgovarajući aminokiselinski derivati tert-butilhinona, sa IC50 vrednostimapojedinih derivata nižim od 10 μM. Rezultati analize ćelijskog ciklusa na HeLa ćelijamaukazuju da je apoptoza jedan od mogućih mehanizama dejstva derivata. Ispitan je uticajkaspaza 3, 8 i 9 na ćelijsku smrt korišćenjem specifičnih kaspaznih inhibitora.Ispitano je i antimikrobno dejstvo derivata prema nizu Gram-pozitivnih i Gramnegativnihbakterija, kao i na tri soja gljivica, pri čemu je zabeležena vrlo dobraaktivnost derivata avarona.Ispitane su interakcije derivata sa biomakromolekulima. SDS gel-ektroforezom imasenom spektrometrijom je potvrđeno da sintetisana jedinjenja ne modifikuju lizozim.Spektrofotometrijskim ispitivanjima je zabeležena pojava hiperhromizma kao posledicainterakcija između hinona i CT-DNA. Utvrđeno je da dolazi do smanjenja intenzitetafluorescencije interkalatora etidijum-bromida i boje Hoechst 33258 koja se vezuje umalu brazdu u kompleksu derivata sa CT-DNA. Spektri cirkularnog dihroizma suukazali na izostanak interkalacije hinona u CT-DNA. Rezultati molekulskogmodelovanja su sugerisali da se derivati smeštaju u malu brazdu DNA. Elektroforetskaispitivanja su potvrdila da ne dolazi do cepanja plazmida pUC19 u prisustvu derivata.Na kraju je utvrđen stepen antioksidativne aktivnosti dobijenih aminokiselinskihderivata hinona., In this doctoral dissertation, a series of amino acid derivatives of thesesquiterpene quinone avarone, isolated from the marine sponge Dysidea avara, as wellas the model compund tert-butylquinone has been synthesized.In vitro cytotoxic activity of all compounds toward human cancer cell lines(HeLa, A549, Fem-X, K562, MDA-MB-453) and normal MRC-5 cell line wasdetermined. It was found that the amino acid derivatives of avarone exhibit a strongeractivity than the corresponding amino acid derivatives of tert-butylquinone, with IC50values of some derivatives less than 10 μM. The results of the cell cycle analysis ofHeLa cells indicate that apoptosis is one of the possible mechanisms of action ofderivatives. The effect of caspases 3, 8, and 9 on cell death by using specific caspaseinhibitors was examined.The antimicrobial effect of the derivatives on the panel of Gram-positive andGram-negative bacteria, as well as on three fungal species, were investigated, wherebyvery good activity of avarone derivatives was observed.Interactions of the derivatives with biomacromolecules were studied. SDS gelelectrophoresisand mass spectrometry confirmed the absence of modifications oflysozyme by any of the synthesized compounds. Spectrophotometric studies haverecorded the occurrence of hyperchromism as a result of interactions between thequinone and CT-DNA. The quenching of the fluorescence of the intercalator ethidiumbromide and of the minor groove binder Hoechst 33258 in the complex with CT-DNAby the derivatives was determined. Circular dichroism spectra demonstrated a nonintercalativebinding mode of the quinone derivatives to CT-DNA. The results ofmolecular modeling suggested that the derivatives bind to the minor groove. Theelectrophoretic pattern showed no cleavage of the pUC19 plasmid in the presence ofany derivatives.Finally, the degree of antioxidant activity of the obtained amino acid derivativesof the quinones was determined.",
publisher = "Универзитет у Београду, Хемијски факултет",
journal = "Универзитет у Београду",
title = "Dobijanje aminokiselinskih derivata avarona i tert-butilhinona i ispitivanje njihove biološke aktivnosti",
url = "https://hdl.handle.net/21.15107/rcub_nardus_9173"
}