TY  - JOUR
AU  - Zornić, Sanja
AU  - Simović Marković, Bojana
AU  - Franich, Andjela A.
AU  - Janjić, Goran
AU  - Jadranin, Milka
AU  - Avdalović, Jelena
AU  - Rajković, Snežana
AU  - Živković, Marija D.
AU  - Arsenijević, Nebojša N.
AU  - Radosavljević, Gordana D.
AU  - Pantić, Jelena
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7213
AB  - Platinum-based drugs are widely recognized efficient anti-tumor agents, but faced with multiple undesirable effects. Here, four dinuclear platinum(II) complexes, [{Pt(1,2-pn)Cl}2(μ-pydz)]Cl2 (C1), [{Pt(ibn)Cl}2(μ-pydz)]Cl2 (C2), [{Pt(1,3-pn)Cl}2(μ-pydz)]Cl2 (C3) and [{Pt(1,3-pnd)Cl}2(μ-pydz)]Cl2 (C4), were designed (pydz is pyridazine, 1,2-pn is ( ±)-1,2-propylenediamine, ibn is 1,2-diamino-2-methylpropane, 1,3-pn is 1,3-propylenediamine, and 1,3-pnd is 1,3-pentanediamine). Interactions and binding ability of C1–C4 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV–Vis, fluorescence emission spectroscopy and molecular docking. Binding affinities of C1–C4 complexes to the bovine serum albumin (BSA) has been monitored by fluorescence emission spectroscopy. The tested complexes exhibit variable cytotoxicity toward different mouse and human tumor cell lines. C2 shows the most potent cytotoxicity, especially against mouse (4T1) and human (MDA-MD468) breast cancer cells in the dose- and time-dependent manner. C2 induces 4T1 and MDA-MD468 cells apoptosis, further documented by the accumulation of cells at sub-G1 phase of cell cycle and increase of executive caspase 3 and caspase 9 levels in 4T1 cells. C2 exhibits anti-proliferative effect through the reduction of cyclin D3 and cyclin E expression and elevation of inhibitor p27 level. Also, C2 downregulates c-Myc and phosphorylated AKT, oncogenes involved in the control of tumor cell proliferation and death. In order to measure the amount of platinum(II) complexes taken up by the cells, the cellular platinum content were quantified. However, C2 failed to inhibit mouse breast cancer growth in vivo. Chemical modifications of tested platinum(II) complexes might be a valuable approach for the improvement of their anti-tumor activity, especially effects in vivo.
PB  - Springer
T2  - Journal of Biological Inorganic Chemistry
T1  - Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand
DO  - 10.1007/s00775-023-02030-0
ER  - 

@article{
author = "Zornić, Sanja and Simović Marković, Bojana and Franich, Andjela A. and Janjić, Goran and Jadranin, Milka and Avdalović, Jelena and Rajković, Snežana and Živković, Marija D. and Arsenijević, Nebojša N. and Radosavljević, Gordana D. and Pantić, Jelena",
year = "2023",
abstract = "Platinum-based drugs are widely recognized efficient anti-tumor agents, but faced with multiple undesirable effects. Here, four dinuclear platinum(II) complexes, [{Pt(1,2-pn)Cl}2(μ-pydz)]Cl2 (C1), [{Pt(ibn)Cl}2(μ-pydz)]Cl2 (C2), [{Pt(1,3-pn)Cl}2(μ-pydz)]Cl2 (C3) and [{Pt(1,3-pnd)Cl}2(μ-pydz)]Cl2 (C4), were designed (pydz is pyridazine, 1,2-pn is ( ±)-1,2-propylenediamine, ibn is 1,2-diamino-2-methylpropane, 1,3-pn is 1,3-propylenediamine, and 1,3-pnd is 1,3-pentanediamine). Interactions and binding ability of C1–C4 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV–Vis, fluorescence emission spectroscopy and molecular docking. Binding affinities of C1–C4 complexes to the bovine serum albumin (BSA) has been monitored by fluorescence emission spectroscopy. The tested complexes exhibit variable cytotoxicity toward different mouse and human tumor cell lines. C2 shows the most potent cytotoxicity, especially against mouse (4T1) and human (MDA-MD468) breast cancer cells in the dose- and time-dependent manner. C2 induces 4T1 and MDA-MD468 cells apoptosis, further documented by the accumulation of cells at sub-G1 phase of cell cycle and increase of executive caspase 3 and caspase 9 levels in 4T1 cells. C2 exhibits anti-proliferative effect through the reduction of cyclin D3 and cyclin E expression and elevation of inhibitor p27 level. Also, C2 downregulates c-Myc and phosphorylated AKT, oncogenes involved in the control of tumor cell proliferation and death. In order to measure the amount of platinum(II) complexes taken up by the cells, the cellular platinum content were quantified. However, C2 failed to inhibit mouse breast cancer growth in vivo. Chemical modifications of tested platinum(II) complexes might be a valuable approach for the improvement of their anti-tumor activity, especially effects in vivo.",
publisher = "Springer",
journal = "Journal of Biological Inorganic Chemistry",
title = "Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand",
doi = "10.1007/s00775-023-02030-0"
}

Zornić, S., Simović Marković, B., Franich, A. A., Janjić, G., Jadranin, M., Avdalović, J., Rajković, S., Živković, M. D., Arsenijević, N. N., Radosavljević, G. D.,& Pantić, J.. (2023). Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand. in Journal of Biological Inorganic Chemistry
Springer..
https://doi.org/10.1007/s00775-023-02030-0

Zornić S, Simović Marković B, Franich AA, Janjić G, Jadranin M, Avdalović J, Rajković S, Živković MD, Arsenijević NN, Radosavljević GD, Pantić J. Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand. in Journal of Biological Inorganic Chemistry. 2023;.
doi:10.1007/s00775-023-02030-0 .

Zornić, Sanja, Simović Marković, Bojana, Franich, Andjela A., Janjić, Goran, Jadranin, Milka, Avdalović, Jelena, Rajković, Snežana, Živković, Marija D., Arsenijević, Nebojša N., Radosavljević, Gordana D., Pantić, Jelena, "Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand" in Journal of Biological Inorganic Chemistry (2023),
https://doi.org/10.1007/s00775-023-02030-0 . .

TY  - JOUR
AU  - Konovalov, Bata
AU  - Đorđević, Ivana
AU  - Franich, Andjela A.
AU  - Šmit, Biljana
AU  - Živković, Marija D.
AU  - Djuran, Miloš I.
AU  - Janjić, Goran
AU  - Rajković, Snežana
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7061
AB  - The hydrolysis of N-acetylated L-methionylglycine dipeptide (Ac-L-Met-Gly) in the presence of dinuclear platinum(II)-aqua complexes with general formula [{Pt(L)(H2O)}2(μ-1,5-nphe)]4+ (1,5-nphe is 1,5-naphthyridine; L is bidentately coordinated ethylenediamine (1w), (±)-1,2-propylenediamine (2w) and 1,3-propylenediamine (3w)) is described in detail. The hydrolytic activity of these complexes was monitored by 1H NMR spectroscopy, which confirmed the regioselective cleavage of the Met-Gly-amide bond in this peptide. Quantum-chemical calculations revealed the primary reaction path with coordination of dipeptide via the terminal amide nitrogen of methionine followed by its coordination for the sulphur atom, in which the decomposition of the resulted platinum(II)-dipeptide complex and the coordination of its glycine residue precedes the hydrolytic cleavage of the Met-Gly amide bond. In the secondary reaction path, in which Ac-L-Met-Gly is coordinated via the methionine sulphur atom, the decomposition of the starting [{Pt(L)(H2O)}2(μ-1,5-nphe)]4+ complex is followed by the regioselective hydrolysis of the investigated dipeptide. The binding affinity of the chloride derivatives of the corresponding dinuclear platinum(II)-aqua complexes, [{Pt(L)Cl}2(μ-1,5-nphe)]2+ (1–3) towards the human serum albumin (HSA), a transport protein, was investigated using electronic absorption and fluorescence emission measurements, and results indicated the static interactions between these complexes and HSA. A docking study revealed a unique binding site on HSA, based on the electrostatic and the hydrogen bonding, which does not have a methionine residue nearby, therefore does not exist danger of HSA hydrolysis by these complexes.
PB  - Elsevier
T2  - Journal of Molecular Structure
T1  - Dinuclear platinum(II) complexes with 1,5-nphe bridging ligand: Spectroscopic and molecular docking study of the interactions with N-acetylated L-methionylglycine and human serum albumin
VL  - 1288
SP  - 135810
DO  - 10.1016/j.molstruc.2023.135810
ER  - 

@article{
author = "Konovalov, Bata and Đorđević, Ivana and Franich, Andjela A. and Šmit, Biljana and Živković, Marija D. and Djuran, Miloš I. and Janjić, Goran and Rajković, Snežana",
year = "2023",
abstract = "The hydrolysis of N-acetylated L-methionylglycine dipeptide (Ac-L-Met-Gly) in the presence of dinuclear platinum(II)-aqua complexes with general formula [{Pt(L)(H2O)}2(μ-1,5-nphe)]4+ (1,5-nphe is 1,5-naphthyridine; L is bidentately coordinated ethylenediamine (1w), (±)-1,2-propylenediamine (2w) and 1,3-propylenediamine (3w)) is described in detail. The hydrolytic activity of these complexes was monitored by 1H NMR spectroscopy, which confirmed the regioselective cleavage of the Met-Gly-amide bond in this peptide. Quantum-chemical calculations revealed the primary reaction path with coordination of dipeptide via the terminal amide nitrogen of methionine followed by its coordination for the sulphur atom, in which the decomposition of the resulted platinum(II)-dipeptide complex and the coordination of its glycine residue precedes the hydrolytic cleavage of the Met-Gly amide bond. In the secondary reaction path, in which Ac-L-Met-Gly is coordinated via the methionine sulphur atom, the decomposition of the starting [{Pt(L)(H2O)}2(μ-1,5-nphe)]4+ complex is followed by the regioselective hydrolysis of the investigated dipeptide. The binding affinity of the chloride derivatives of the corresponding dinuclear platinum(II)-aqua complexes, [{Pt(L)Cl}2(μ-1,5-nphe)]2+ (1–3) towards the human serum albumin (HSA), a transport protein, was investigated using electronic absorption and fluorescence emission measurements, and results indicated the static interactions between these complexes and HSA. A docking study revealed a unique binding site on HSA, based on the electrostatic and the hydrogen bonding, which does not have a methionine residue nearby, therefore does not exist danger of HSA hydrolysis by these complexes.",
publisher = "Elsevier",
journal = "Journal of Molecular Structure",
title = "Dinuclear platinum(II) complexes with 1,5-nphe bridging ligand: Spectroscopic and molecular docking study of the interactions with N-acetylated L-methionylglycine and human serum albumin",
volume = "1288",
pages = "135810",
doi = "10.1016/j.molstruc.2023.135810"
}

Konovalov, B., Đorđević, I., Franich, A. A., Šmit, B., Živković, M. D., Djuran, M. I., Janjić, G.,& Rajković, S.. (2023). Dinuclear platinum(II) complexes with 1,5-nphe bridging ligand: Spectroscopic and molecular docking study of the interactions with N-acetylated L-methionylglycine and human serum albumin. in Journal of Molecular Structure
Elsevier., 1288, 135810.
https://doi.org/10.1016/j.molstruc.2023.135810

Konovalov B, Đorđević I, Franich AA, Šmit B, Živković MD, Djuran MI, Janjić G, Rajković S. Dinuclear platinum(II) complexes with 1,5-nphe bridging ligand: Spectroscopic and molecular docking study of the interactions with N-acetylated L-methionylglycine and human serum albumin. in Journal of Molecular Structure. 2023;1288:135810.
doi:10.1016/j.molstruc.2023.135810 .

Konovalov, Bata, Đorđević, Ivana, Franich, Andjela A., Šmit, Biljana, Živković, Marija D., Djuran, Miloš I., Janjić, Goran, Rajković, Snežana, "Dinuclear platinum(II) complexes with 1,5-nphe bridging ligand: Spectroscopic and molecular docking study of the interactions with N-acetylated L-methionylglycine and human serum albumin" in Journal of Molecular Structure, 1288 (2023):135810,
https://doi.org/10.1016/j.molstruc.2023.135810 . .