TY  - 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 . .

TY  - JOUR
AU  - Međedović, Milica
AU  - Mijatović, Aleksandar
AU  - Baošić, Rada
AU  - Lazić, Dejan
AU  - Milanović, Žiko
AU  - Marković, Zoran
AU  - Milovanović, Jelena
AU  - Arsenijević, Dragana
AU  - Stojanović, Bojana
AU  - Arsenijević, Miloš
AU  - Milovanović, Marija
AU  - Petrović, Biljana
AU  - Rilak Simović, Ana
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6353
AB  - In order to discover new anticancer drugs, novel ruthenium(III) complexes [Ru(L)Cl(H2O)], where L is tetradentate Schiff base bis(acetylacetone)ethylendiimine (acacen, 1), bis(benzoylacetone)ethylendiimine (bzacen, 2), (acetylacetone)(benzoylaceton)ethylendiimine (acacbzacen, 3), bis(acetylacetone)propylendiimine (acacpn, 4), bis(benzoylacetone)propylendiimine (bzacpn, 5) or (acetylacetone)(benzoylaceton)propylendiimine (acacbzacpn, 6), were synthesized. The complexes 1 – 6 were characterized by elemental analysis, molar conductometry, and by various spectroscopic techniques, such as UV–Vis, IR, EPR, and ESI-MS. Based on in vitro DNA/BSA experiments, complexes 2 (bzacen) and 5 (bzacpn) with two aromatic rings showed the highest DNA/BSA-activity, suggesting that the presence of the aromatic ring on the tetradentate Schiff base ligand contributes to increased activity. Moreover, these two compounds showed the highest cytotoxic effects toward human, A549 and murine LLC1 lung cancer cells. These complexes altered the ratio of anti- and pro-apoptotic molecules and induced apoptosis of A549 cells. Further, complexes 2 and 5 reduced the percentage of Mcl1 and Bcl2 expressing LLC1 cells, induced their apoptotic death and exerted an antiproliferative effect against LLC1. Finally, complex 5 reduced the volume of mouse primary heterotopic Lewis lung cancer, while complex 2 reduced the incidence and mean number of metastases per lung. Additionally, molecular docking with DNA revealed that the reduced number of aromatic rings or their absence causes lower intercalative properties of the complexes in order: 2 > 5 > 6 > 3 > 4 > 1. It was observed that conventional hydrogen bonds and hydrophobic interactions contribute to the stabilization of the structures of complex-DNA. A molecular docking study with BSA revealed a predominance of 1 – 6 in binding affinity to the active site III, a third D-shaped hydrophobic pocket within subdomain IB.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes
VL  - 248
SP  - 112363
DO  - 10.1016/j.jinorgbio.2023.112363
ER  - 

@article{
author = "Međedović, Milica and Mijatović, Aleksandar and Baošić, Rada and Lazić, Dejan and Milanović, Žiko and Marković, Zoran and Milovanović, Jelena and Arsenijević, Dragana and Stojanović, Bojana and Arsenijević, Miloš and Milovanović, Marija and Petrović, Biljana and Rilak Simović, Ana",
year = "2023",
abstract = "In order to discover new anticancer drugs, novel ruthenium(III) complexes [Ru(L)Cl(H2O)], where L is tetradentate Schiff base bis(acetylacetone)ethylendiimine (acacen, 1), bis(benzoylacetone)ethylendiimine (bzacen, 2), (acetylacetone)(benzoylaceton)ethylendiimine (acacbzacen, 3), bis(acetylacetone)propylendiimine (acacpn, 4), bis(benzoylacetone)propylendiimine (bzacpn, 5) or (acetylacetone)(benzoylaceton)propylendiimine (acacbzacpn, 6), were synthesized. The complexes 1 – 6 were characterized by elemental analysis, molar conductometry, and by various spectroscopic techniques, such as UV–Vis, IR, EPR, and ESI-MS. Based on in vitro DNA/BSA experiments, complexes 2 (bzacen) and 5 (bzacpn) with two aromatic rings showed the highest DNA/BSA-activity, suggesting that the presence of the aromatic ring on the tetradentate Schiff base ligand contributes to increased activity. Moreover, these two compounds showed the highest cytotoxic effects toward human, A549 and murine LLC1 lung cancer cells. These complexes altered the ratio of anti- and pro-apoptotic molecules and induced apoptosis of A549 cells. Further, complexes 2 and 5 reduced the percentage of Mcl1 and Bcl2 expressing LLC1 cells, induced their apoptotic death and exerted an antiproliferative effect against LLC1. Finally, complex 5 reduced the volume of mouse primary heterotopic Lewis lung cancer, while complex 2 reduced the incidence and mean number of metastases per lung. Additionally, molecular docking with DNA revealed that the reduced number of aromatic rings or their absence causes lower intercalative properties of the complexes in order: 2 > 5 > 6 > 3 > 4 > 1. It was observed that conventional hydrogen bonds and hydrophobic interactions contribute to the stabilization of the structures of complex-DNA. A molecular docking study with BSA revealed a predominance of 1 – 6 in binding affinity to the active site III, a third D-shaped hydrophobic pocket within subdomain IB.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes",
volume = "248",
pages = "112363",
doi = "10.1016/j.jinorgbio.2023.112363"
}

Međedović, M., Mijatović, A., Baošić, R., Lazić, D., Milanović, Ž., Marković, Z., Milovanović, J., Arsenijević, D., Stojanović, B., Arsenijević, M., Milovanović, M., Petrović, B.,& Rilak Simović, A.. (2023). Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes. in Journal of Inorganic Biochemistry
Elsevier., 248, 112363.
https://doi.org/10.1016/j.jinorgbio.2023.112363

Međedović M, Mijatović A, Baošić R, Lazić D, Milanović Ž, Marković Z, Milovanović J, Arsenijević D, Stojanović B, Arsenijević M, Milovanović M, Petrović B, Rilak Simović A. Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes. in Journal of Inorganic Biochemistry. 2023;248:112363.
doi:10.1016/j.jinorgbio.2023.112363 .

Međedović, Milica, Mijatović, Aleksandar, Baošić, Rada, Lazić, Dejan, Milanović, Žiko, Marković, Zoran, Milovanović, Jelena, Arsenijević, Dragana, Stojanović, Bojana, Arsenijević, Miloš, Milovanović, Marija, Petrović, Biljana, Rilak Simović, Ana, "Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes" in Journal of Inorganic Biochemistry, 248 (2023):112363,
https://doi.org/10.1016/j.jinorgbio.2023.112363 . .