Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent
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2023
Authors
Mrkalić, EminaŠmit, Biljana
Matić, Sanja
Jelić, Ratomir

Ćendić Serafinović, Marina
Gligorijević, Nevenka
Čavić, Milena

Aranđelović, Sandra

Grgurić-Šipka, Sanja
Soldatović, Tanja
Article (Published version)

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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 protect...ive
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.
Keywords:
Heterometallic complexes / Structure-reactivity correlation / Antitumor agentsSource:
J. Inorg. Biochem., 2023, 240Publisher:
- Elsevier
Funding / projects:
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200252 (State University of Novi Pazar) (RS-200252)
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200378 (Institute of Information Technology) (RS-200378)
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200043 (Institute of Oncology and Radiology of Serbia, Belgrade) (RS-200043)
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Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Mrkalić, Emina AU - Šmit, Biljana AU - Matić, Sanja AU - Jelić, Ratomir AU - Ćendić Serafinović, Marina AU - Gligorijević, Nevenka AU - Čavić, Milena AU - Aranđelović, Sandra AU - Grgurić-Šipka, Sanja AU - Soldatović, Tanja PY - 2023 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5880 AB - 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. PB - Elsevier T2 - J. Inorg. Biochem. T1 - Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent VL - 240 DO - https://doi.org/10.1016/j.jinorgbio.2022.112100 ER -
@article{ author = "Mrkalić, Emina and Šmit, Biljana and Matić, Sanja and Jelić, Ratomir and Ćendić Serafinović, Marina and Gligorijević, Nevenka and Čavić, Milena and Aranđelović, Sandra and Grgurić-Šipka, Sanja and Soldatović, Tanja", year = "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.", publisher = "Elsevier", journal = "J. Inorg. Biochem.", title = "Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent", volume = "240", doi = "https://doi.org/10.1016/j.jinorgbio.2022.112100" }
Mrkalić, E., Šmit, B., Matić, S., Jelić, R., Ćendić Serafinović, M., Gligorijević, N., Čavić, M., Aranđelović, S., Grgurić-Šipka, S.,& Soldatović, T.. (2023). Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent. in J. Inorg. Biochem. Elsevier., 240. https://doi.org/https://doi.org/10.1016/j.jinorgbio.2022.112100
Mrkalić E, Šmit B, Matić S, Jelić R, Ćendić Serafinović M, Gligorijević N, Čavić M, Aranđelović S, Grgurić-Šipka S, Soldatović T. Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent. in J. Inorg. Biochem.. 2023;240. doi:https://doi.org/10.1016/j.jinorgbio.2022.112100 .
Mrkalić, Emina, Šmit, Biljana, Matić, Sanja, Jelić, Ratomir, Ćendić Serafinović, Marina, Gligorijević, Nevenka, Čavić, Milena, Aranđelović, Sandra, Grgurić-Šipka, Sanja, Soldatović, Tanja, "Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent" in J. Inorg. Biochem., 240 (2023), https://doi.org/https://doi.org/10.1016/j.jinorgbio.2022.112100 . .