Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/19089
Title: Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agents
Authors: V. Soldatovic, Tanja
Šmit, Biljana
Mrkalić, Emina
Matić, Sanja
Jelic, Ratomir
Serafinović, Marina Ćendić
Gligorijević, Nevenka
Cavic, Milena
Aranđelović, Sandra
Grguric-Sipka, Sanja
Issue Date: 2023
Abstract: The four novel complexes [{cis-PtCl(NH3)2(μ-4,4'-bipyridyl)ZnCl(terpy)}](ClO4)2 (C1), [{trans-PtCl(NH3)2(μ-4,4'-bipyridyl)ZnCl(terpy)}](ClO4)2 (C2), [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (C3) and [{trans-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (C4) (where terpy = 2,2':6',2''-terpyridine) were synthesized and characterized. Acid-base titrations and concentration dependent kinetic measurements for the reactions with biologically relevant ligands such as guanosine-5'-monophosphate (5'-GMP), inosine-5'-monophosphate (5'-IMP) and glutathione (GSH), were studied at pH 7.4 and 37 °C. The binding of the heterometallic bridged cis- or trans-Pt(II)-Zn(II) complexes to calf thymus DNA (CT-DNA) was studied by UV absorption and fluorescence emission spectroscopy and molecular docking. The results indicated that the complexes bind strongly to DNA, through groove binding, hydrogen bonds, and hydrophobic or electrostatic interaction. The possible in vitro DNA protective effect of cis- and trans-Pt-L-Zn complexes has shown that C3 had significant dose-dependent DNA-protective effect and the same ability to inhibit peroxyl as well as hydroxyl radicals. Antiproliferative effect of the complexes, mRNA expression of apoptosis and repair-related genes after treatment in cancer cells indicated that newly synthesized C2 exhibited highly selective cytotoxicity toward colon carcinoma HCT116 cells. Only treatment with trans analog C2 induced effect similar to the typical DNA damaging agent such as cisplatin, characterized by p53 mediated cell response, cell cycle arrest and certain induction of apoptotic related genes. Both cis- and trans-isomers C1 and C2 showed potency to elicit expression of PARP1 mRNA and in vitro DNA binding.
URI: https://scidar.kg.ac.rs/handle/123456789/19089
Type: article
DOI: 10.1016/j.jinorgbio.2022.112100
ISSN: 0162-0134
SCOPUS: 2-s2.0-85144083760
Appears in Collections:Faculty of Medical Sciences, Kragujevac
Institute for Information Technologies, Kragujevac

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