Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand
Само за регистроване кориснике
2023
Аутори
Zornić, SanjaSimović Marković, Bojana
Franich, Andjela A.
Janjić, Goran
Jadranin, Milka
Avdalović, Jelena
Rajković, Snežana
Živković, Marija D.
Arsenijević, Nebojša N.
Radosavljević, Gordana D.
Pantić, Jelena
Чланак у часопису (Објављена верзија)
,
The Authors under exclusive licence to Society for Biological Inorganic Chemistry (SBIC)
Метаподаци
Приказ свих података о документуАпстракт
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) bre...ast 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.
Кључне речи:
Dinuclear platinum(II) complexes / DNA/BSA binding / Anti-tumor activity / ·Breast cancer cells / Apoptosis / Cell proliferationИзвор:
Journal of Biological Inorganic Chemistry, 2023Издавач:
- Springer
DOI: 10.1007/s00775-023-02030-0
ISSN: 1432-1327; 0949-8257
Scopus: 2-s2.0-85179670767
Институција/група
IHTMTY - 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 . .