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  - Dimitrijević, Jelena
AU  - Solovjova, Natalija
AU  - Bukonjić, Andriana M.
AU  - Tomović, Dušan Lj.
AU  - Milinković, Mirjana
AU  - Caković, Angelina
AU  - Bogojeski, Jovana
AU  - Ratković, Zoran R.
AU  - Janjić, Goran
AU  - Rakić, Aleksandra
AU  - Arsenijević, Nebojša N.
AU  - Milovanović, Marija Z.
AU  - Milovanović, Jelena Z.
AU  - Radić, Gordana P.
AU  - Jevtić, Verica V.
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7060
AB  - The numerous side effects of platinum based chemotherapy has led to the design of new therapeutics with platinum replaced by another transition metal. Here, we investigated the interactions of previously reported copper(II) complexes containing S-isoalkyl derivatives, the salicylic acid with guanosine-5′-monophosphate and calf thymus DNA (CT-DNA) and their antitumor effects, in a colon carcinoma model. All three copper(II) complexes exhibited an affinity for binding to CT-DNA, but there was no indication of intercalation or the displacement of ethidium bromide. Molecular docking studies revealed a significant affinity of the complexes for binding to the minor groove of B-form DNA, which coincided with DNA elongation, and a higher affinity for binding to Z-form DNA, supporting the hypothesis that the complex binding to CT-DNA induces a local transition from B-form to Z-form DNA. These complexes show a moderate, but selective cytotoxic effect toward colon cancer cells in vitro. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acid showed the highest cytotoxic effect, arrested tumor cells in the G2/M phase of the cell cycle, and significantly reduced the expression of inflammatory molecules pro-IL-1β, TNF-α, ICAM-1, and VCAM-1 in the tissue of primary heterotopic murine colon cancer, which was accompanied by a significantly reduced tumor growth and metastases in the lung and liver.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - Docking studies, cytotoxicity evaluation and interactions of binuclear copper(ii) complexes with s-isoalkyl derivatives of thiosalicylic acid with some relevant biomolecules
VL  - 24
IS  - 15
SP  - 12504
DO  - 10.3390/ijms241512504
ER  - 

@article{
author = "Dimitrijević, Jelena and Solovjova, Natalija and Bukonjić, Andriana M. and Tomović, Dušan Lj. and Milinković, Mirjana and Caković, Angelina and Bogojeski, Jovana and Ratković, Zoran R. and Janjić, Goran and Rakić, Aleksandra and Arsenijević, Nebojša N. and Milovanović, Marija Z. and Milovanović, Jelena Z. and Radić, Gordana P. and Jevtić, Verica V.",
year = "2023",
abstract = "The numerous side effects of platinum based chemotherapy has led to the design of new therapeutics with platinum replaced by another transition metal. Here, we investigated the interactions of previously reported copper(II) complexes containing S-isoalkyl derivatives, the salicylic acid with guanosine-5′-monophosphate and calf thymus DNA (CT-DNA) and their antitumor effects, in a colon carcinoma model. All three copper(II) complexes exhibited an affinity for binding to CT-DNA, but there was no indication of intercalation or the displacement of ethidium bromide. Molecular docking studies revealed a significant affinity of the complexes for binding to the minor groove of B-form DNA, which coincided with DNA elongation, and a higher affinity for binding to Z-form DNA, supporting the hypothesis that the complex binding to CT-DNA induces a local transition from B-form to Z-form DNA. These complexes show a moderate, but selective cytotoxic effect toward colon cancer cells in vitro. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acid showed the highest cytotoxic effect, arrested tumor cells in the G2/M phase of the cell cycle, and significantly reduced the expression of inflammatory molecules pro-IL-1β, TNF-α, ICAM-1, and VCAM-1 in the tissue of primary heterotopic murine colon cancer, which was accompanied by a significantly reduced tumor growth and metastases in the lung and liver.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "Docking studies, cytotoxicity evaluation and interactions of binuclear copper(ii) complexes with s-isoalkyl derivatives of thiosalicylic acid with some relevant biomolecules",
volume = "24",
number = "15",
pages = "12504",
doi = "10.3390/ijms241512504"
}

Dimitrijević, J., Solovjova, N., Bukonjić, A. M., Tomović, D. Lj., Milinković, M., Caković, A., Bogojeski, J., Ratković, Z. R., Janjić, G., Rakić, A., Arsenijević, N. N., Milovanović, M. Z., Milovanović, J. Z., Radić, G. P.,& Jevtić, V. V.. (2023). Docking studies, cytotoxicity evaluation and interactions of binuclear copper(ii) complexes with s-isoalkyl derivatives of thiosalicylic acid with some relevant biomolecules. in International Journal of Molecular Sciences
MDPI., 24(15), 12504.
https://doi.org/10.3390/ijms241512504

Dimitrijević J, Solovjova N, Bukonjić AM, Tomović DL, Milinković M, Caković A, Bogojeski J, Ratković ZR, Janjić G, Rakić A, Arsenijević NN, Milovanović MZ, Milovanović JZ, Radić GP, Jevtić VV. Docking studies, cytotoxicity evaluation and interactions of binuclear copper(ii) complexes with s-isoalkyl derivatives of thiosalicylic acid with some relevant biomolecules. in International Journal of Molecular Sciences. 2023;24(15):12504.
doi:10.3390/ijms241512504 .

Dimitrijević, Jelena, Solovjova, Natalija, Bukonjić, Andriana M., Tomović, Dušan Lj., Milinković, Mirjana, Caković, Angelina, Bogojeski, Jovana, Ratković, Zoran R., Janjić, Goran, Rakić, Aleksandra, Arsenijević, Nebojša N., Milovanović, Marija Z., Milovanović, Jelena Z., Radić, Gordana P., Jevtić, Verica V., "Docking studies, cytotoxicity evaluation and interactions of binuclear copper(ii) complexes with s-isoalkyl derivatives of thiosalicylic acid with some relevant biomolecules" in International Journal of Molecular Sciences, 24, no. 15 (2023):12504,
https://doi.org/10.3390/ijms241512504 . .