Naslov (srp)

Strukturna, teorijska i antitumorska ispitivanja dinuklearnih kompleksa platine(II) i paladijuma(II) sa aromatičnim N-heterocikličnim mostnim ligandima

Autor

Franich, Anđela, 1991-

Doprinosi

Rajković, Snežana, 1955-
Janjić, Goran, 1977-
Đuran, Miloš, 1952-
Anđelković, Katarina, 1957-
Petrović, Biljana, 1970-
Živković, Marija, 1979-
Bogojeski, Jovana, 1980-

Opis (srp)

U okviru ove doktorske disertacije prikazana je sinteza dinuklearnih platina(II) i paladijum(II)kompleksa, [{M(en)Cl}2(μ-L)]2+, M je Pt(II) ili Pd(II), en je bidentatno koordinovanetilendiamin, a L je mostni ligand 4,4ʼ-bipiridin (Pt1 i Pd1), 1,2-bis(4-piridil)etan (Pt2 i Pd2),1,2-bis(4-piridil)etilen (Pt3 i Pd3), hinoksalin (Pd4), hinazolin (Pd5) i ftalazin (Pd6).Na osnovu rezultata elementalne mikroanalize, NMR (1H i 13C) i IR spektroskopije kao iUV-Vis spektrofotometrije potvrđena je struktura sintetisanih dinuklearnih kompleksa.Struktura Pt1-Pt3 kompleksa je potvrđena i na osnovu rezultata masene spektroskopije.Interakcije Pt1-Pt3 kompleksa sa CT-DNK ispitivane su primenom UV-Visspektrofotometrije, fluorescentne i IR spektroskopije, merenjem viskoziteta, gel elektroforezomi molekulskim dokingom. Na osnovu dobijenih rezultata može se zaključiti da planarni1,2-bis(4-piridil)etilen mostni ligand uslovljava interkalaciju Pt3 kompleksa u CT-DNK, dokse Pt1 i Pt2 kompleksi vezuju za fosfatne grupe DNK heliksa. Hidrolizom Pt1-Pt3 kompleksanastaju Pt1W-Pt3W akva kompleksi koji se vezuju za DNK premošćavanjem malog žljeba.Rezultati UV-Vis spektrofotometrije, fluorescentne spektroskopije i merenje viskozitetapokazuju da paladijum(II) kompleksi interkaliraju u CT-DNK gde mostni ligandi imaju važanuticaj na jačinu ostvarene veze. Pt1-Pt3 kompleksi prevazilaze rezistentnost ispitivanih ćelijakao i anti-angeogeni terapeutski potencijal sunitiniba, dok Pt3 kompleks pokazuje najvećicitotoksični potencijal u odnosu na ispitivane ćelijske linije. In vitro ispitivanja citotoksičnogpotencijala Pd1-Pd6 kompleksa pokazuju da ovi kompleksi izazivaju apoptozu ispitivanihćelija sa smanjenom ekspresijom Ki-67, a na nekim ćelijama pokazuju bolju aktivnost odcisplatine.

Opis (srp)

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Opis (eng)

In this doctoral dissertation is presented the synthesis of dinuclear platinum(II) andpalladium(II) complexes, [{M(en)Cl}2(μ-L)]2+, where M is Pt(II) or Pd(II), en is bidentatecoordinated ethylenediamine, while L is bridging ligand 4,4ʼ-bipyridine (Pt1 and Pd1),1,2-bis(4-pyridyl)ethane (Pt2 and Pd2), 1,2-bis(4-pyridyl)ethylene (Pt3 and Pd3), quinoxaline(Pd4), quinazoline (Pd5) and phthalazine (Pd6). The structure of synthesized dinuclearcomplexes was confirmed by elemental microanalysis, NMR (1H and 13C) and IR spectroscopy,as well as UV-Vis spectrophotometry. The structure of the Pt1-Pt3 complexes was alsoconfirmed based on the results of mass spectroscopy. The interactions of the Pt1-Pt3 complexeswith CT-DNA were investigated by UV-Vis spectrophotometry, fluorescence and IRspectroscopy, viscosity measurement, gel electrophoresis and molecular docking. Based on theobtained results of the mentioned methods, it can be concluded that the planar1,2-bis(4-pyridyl)ethylene bridging ligand conditions the intercalation of the Pt3 complex inCT-DNA, while the Pt1 and Pt2 complexes bind to the phosphate groups of the DNA helix.Hydrolysis of the Pt1-Pt3 complex produced Pt1W-Pt3W aqua complexes that bind to DNAby the minor groove covering. The results of UV-Vis spectrophotometry, fluorescencespectroscopy and viscosity measurement showed that palladium(II) complexes intercalate inCT-DNA while bridging ligands have an important influence on the strength of the bond.Pt1-Pt3 complexes overcome the resistance of the tested cells as well as the anti-angiogenictherapeutic potential of sunitinib, while the Pt3 complex showed the highest cytotoxic potentialagainst tested cell lines. In vitro investigation of cytotoxicity of the Pd1-Pd6 complexes showedthat these complexes induce apoptosis of the examined cells with reduced expression of Ki-67,and on some tested cells complexes showed better activity than cisplatin.

Jezik

srpski

Datum

2025

Licenca

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Creative Commons CC BY-NC-SA 3.0 AT - Creative Commons Autorstvo - Nekomercijalno - Deliti pod istim uslovima 3.0 Austria License.

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