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 . .

TY  - JOUR
AU  - Franich, Andjela
AU  - Đorđević, Ivana S.
AU  - Živković, Marija D.
AU  - Rajković, Snežana
AU  - Janjić, Goran
AU  - Đuran, Miloš
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4832
AB  - The mechanism of action of most approved drugs in use today is based on their binding to specific proteins or DNA. One
of the achievements of this research is a new perspective for recognition of binding modes to DNA by monitoring of
changes in measured and stoichiometric values of absorbance at 260 nm. UV–Vis and IR spectroscopy, gel electrophoresis
and docking study were used for investigation of binding properties of three dinuclear platinum(II) complexes containing
different pyridine-based bridging ligands, [{Pt(en)Cl}2(μ-4,4’-bipy)]Cl2・2H2O (Pt1), [{Pt(en)Cl}2(μ-bpa)]Cl2・4H2O (Pt2)
and [{Pt(en)Cl}2(μ-bpe)]Cl2・4H2O (Pt3) to DNA (4,4’-bipy, bpa and bpe are 4,4′-bipyridine, 1,2-bis(4-pyridyl)ethane and
1,2-bis(4-pyridyl)ethene, respectively). In contrast to the system with well-known intercalated ligand (EtBr), covalently bound
ligand (cis-Pt) and with minor groove binder (Hoechst 33258), which do not have significant differences in measured and
stoichiometric values, the most pronounced deviations are recorded for two dinuclear platinum(II) complexes (Pt1 and Pt2),
as a consequence of complex binding to the phosphate backbone and bending of DNA helix. The hydrolysis of complexes
and changes in DNA conformation were also analysed as phenomena that may have an impact on the changes in absorbance.
PB  - Springer
T2  - Journal of Biological Inorganic Chemistry
T1  - Dinuclear platinum(II) complexes as the pattern for phosphate backbone binding: a new perspective for recognition of binding modes to DNA
VL  - 27
SP  - 65
EP  - 79
DO  - 10.1007/s00775-021-01911-6
ER  - 

@article{
author = "Franich, Andjela and Đorđević, Ivana S. and Živković, Marija D. and Rajković, Snežana and Janjić, Goran and Đuran, Miloš",
year = "2022",
abstract = "The mechanism of action of most approved drugs in use today is based on their binding to specific proteins or DNA. One
of the achievements of this research is a new perspective for recognition of binding modes to DNA by monitoring of
changes in measured and stoichiometric values of absorbance at 260 nm. UV–Vis and IR spectroscopy, gel electrophoresis
and docking study were used for investigation of binding properties of three dinuclear platinum(II) complexes containing
different pyridine-based bridging ligands, [{Pt(en)Cl}2(μ-4,4’-bipy)]Cl2・2H2O (Pt1), [{Pt(en)Cl}2(μ-bpa)]Cl2・4H2O (Pt2)
and [{Pt(en)Cl}2(μ-bpe)]Cl2・4H2O (Pt3) to DNA (4,4’-bipy, bpa and bpe are 4,4′-bipyridine, 1,2-bis(4-pyridyl)ethane and
1,2-bis(4-pyridyl)ethene, respectively). In contrast to the system with well-known intercalated ligand (EtBr), covalently bound
ligand (cis-Pt) and with minor groove binder (Hoechst 33258), which do not have significant differences in measured and
stoichiometric values, the most pronounced deviations are recorded for two dinuclear platinum(II) complexes (Pt1 and Pt2),
as a consequence of complex binding to the phosphate backbone and bending of DNA helix. The hydrolysis of complexes
and changes in DNA conformation were also analysed as phenomena that may have an impact on the changes in absorbance.",
publisher = "Springer",
journal = "Journal of Biological Inorganic Chemistry",
title = "Dinuclear platinum(II) complexes as the pattern for phosphate backbone binding: a new perspective for recognition of binding modes to DNA",
volume = "27",
pages = "65-79",
doi = "10.1007/s00775-021-01911-6"
}

Franich, A., Đorđević, I. S., Živković, M. D., Rajković, S., Janjić, G.,& Đuran, M.. (2022). Dinuclear platinum(II) complexes as the pattern for phosphate backbone binding: a new perspective for recognition of binding modes to DNA. in Journal of Biological Inorganic Chemistry
Springer., 27, 65-79.
https://doi.org/10.1007/s00775-021-01911-6

Franich A, Đorđević IS, Živković MD, Rajković S, Janjić G, Đuran M. Dinuclear platinum(II) complexes as the pattern for phosphate backbone binding: a new perspective for recognition of binding modes to DNA. in Journal of Biological Inorganic Chemistry. 2022;27:65-79.
doi:10.1007/s00775-021-01911-6 .

Franich, Andjela, Đorđević, Ivana S., Živković, Marija D., Rajković, Snežana, Janjić, Goran, Đuran, Miloš, "Dinuclear platinum(II) complexes as the pattern for phosphate backbone binding: a new perspective for recognition of binding modes to DNA" in Journal of Biological Inorganic Chemistry, 27 (2022):65-79,
https://doi.org/10.1007/s00775-021-01911-6 . .

TY  - JOUR
AU  - Bondžić, Aleksandra M.
AU  - Žakula, Jelena J.
AU  - Korićanac, Lela
AU  - Keta, Otilija D.
AU  - Janjić, Goran
AU  - Đorđević, Ivana S.
AU  - Rajković, Snežana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5412
AB  - Herein, the stability, lipophilicity, in vitro cytotoxicity, and influence on acetylcholinesterase of five dinuclear platinum(II) complexes with the general formula [{Pt(en)Cl}2(μ-L)]2+ (L is a different aromatic nitrogen-containing heterocyclic bridging ligands pyrazine (pz, Pt1), pyridazine (pydz, Pt2), quinoxaline (qx, Pt3), phthalazine (phtz, Pt4) and quinazoline (qz, Pt5), while en is bidentate coordinated ethylenediamine) were evaluated. The most active analyzed platinum complexes induced time-dependent growth inhibition of A375, HeLa, PANC-1, and MRC-5 cells. The best efficiency was achieved on HeLa and PANC-1 cells for Pt1, Pt2, and Pt3 at the highest concentration, while Pt1 was significantly more potent than cisplatin at a lower concentration. Additionally, a lower effect on normal cells was observed compared to cisplatin, which may indicate potentially fewer side effects of these complexes. Selected complexes induce reactive oxygen species and apoptosis on tumor cell lines. The most potent reversible acetylcholinesterase (AChE) inhibitors were Pt2, Pt4, and Pt5. Pt1 showed similar inhibitory potential toward AChE as cisplatin, but a different type of inhibition, which could contribute to lower neurotoxicity. Docking studies revealed that Pt2 and Pt4 were bound to the active gorge above the catalytic triad. In contrast, the other complexes were bound to the edge of the active gorge without impeding the approach to the catalytic triad. According to this, Pt1 represents a promising compound with potent anticancer properties, high selectivity, and low neurotoxicity.
PB  - Elsevier
T2  - Chemico-Biological Interactions
T1  - Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action
VL  - 351
SP  - 109708
DO  - 10.1016/j.cbi.2021.109708
ER  - 

@article{
author = "Bondžić, Aleksandra M. and Žakula, Jelena J. and Korićanac, Lela and Keta, Otilija D. and Janjić, Goran and Đorđević, Ivana S. and Rajković, Snežana",
year = "2022",
abstract = "Herein, the stability, lipophilicity, in vitro cytotoxicity, and influence on acetylcholinesterase of five dinuclear platinum(II) complexes with the general formula [{Pt(en)Cl}2(μ-L)]2+ (L is a different aromatic nitrogen-containing heterocyclic bridging ligands pyrazine (pz, Pt1), pyridazine (pydz, Pt2), quinoxaline (qx, Pt3), phthalazine (phtz, Pt4) and quinazoline (qz, Pt5), while en is bidentate coordinated ethylenediamine) were evaluated. The most active analyzed platinum complexes induced time-dependent growth inhibition of A375, HeLa, PANC-1, and MRC-5 cells. The best efficiency was achieved on HeLa and PANC-1 cells for Pt1, Pt2, and Pt3 at the highest concentration, while Pt1 was significantly more potent than cisplatin at a lower concentration. Additionally, a lower effect on normal cells was observed compared to cisplatin, which may indicate potentially fewer side effects of these complexes. Selected complexes induce reactive oxygen species and apoptosis on tumor cell lines. The most potent reversible acetylcholinesterase (AChE) inhibitors were Pt2, Pt4, and Pt5. Pt1 showed similar inhibitory potential toward AChE as cisplatin, but a different type of inhibition, which could contribute to lower neurotoxicity. Docking studies revealed that Pt2 and Pt4 were bound to the active gorge above the catalytic triad. In contrast, the other complexes were bound to the edge of the active gorge without impeding the approach to the catalytic triad. According to this, Pt1 represents a promising compound with potent anticancer properties, high selectivity, and low neurotoxicity.",
publisher = "Elsevier",
journal = "Chemico-Biological Interactions",
title = "Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action",
volume = "351",
pages = "109708",
doi = "10.1016/j.cbi.2021.109708"
}

Bondžić, A. M., Žakula, J. J., Korićanac, L., Keta, O. D., Janjić, G., Đorđević, I. S.,& Rajković, S.. (2022). Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action. in Chemico-Biological Interactions
Elsevier., 351, 109708.
https://doi.org/10.1016/j.cbi.2021.109708

Bondžić AM, Žakula JJ, Korićanac L, Keta OD, Janjić G, Đorđević IS, Rajković S. Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action. in Chemico-Biological Interactions. 2022;351:109708.
doi:10.1016/j.cbi.2021.109708 .

Bondžić, Aleksandra M., Žakula, Jelena J., Korićanac, Lela, Keta, Otilija D., Janjić, Goran, Đorđević, Ivana S., Rajković, Snežana, "Cytotoxic activity and influence on acetylcholinesterase of series dinuclear platinum(II) complexes with aromatic nitrogen-containing heterocyclic bridging ligands: Insights in the mechanisms of action" in Chemico-Biological Interactions, 351 (2022):109708,
https://doi.org/10.1016/j.cbi.2021.109708 . .

TY  - JOUR
AU  - Franich, Andjela
AU  - Živković, Marija D.
AU  - Ilić-Tomić, Tatjana
AU  - Đorđević, Ivana
AU  - Nikodinović-Runić, Jasmina
AU  - Pavić, Aleksandar
AU  - Janjić, Goran
AU  - Rajković, Snežana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3883
AB  - New anticancer platinum(II) compounds simultaneously targeting tumor cells and tumor-derived neoangiogenesis, with new DNA interacting mode and large therapeutic window are appealing alternative to improve efficacy of clinical platinum chemotherapeutics. Herein, we describe three novel dinuclear [{Pt(en)Cl}2(μ-L)]2+ complexes with different pyridine-like bridging ligands (L), 4,4′-bipyridine (Pt1), 1,2-bis(4-pyridyl)ethane (Pt2) and 1,2-bis(4-pyridyl)ethene (Pt3), which highly, positively charged aqua derivatives, [{Pt(en)(H2O)}2(μ-L)]4+, interact with the phosphate backbone forming DNA-Pt adducts with an unique and previously undescribed binding mode, called a minor groove covering. The results of this study suggested that the new binding mode of the aqua-Pt(II) complexes with DNA could be attributed to the higher anticancer activities of their chloride analogues. All three compounds, particularly complex [{Pt(en)Cl}2(μ-4,4′-bipy)]Cl2·2H2O (4,4′-bipy is 4,4′-bipyridine) (Pt1), overcame cisplatin resistance in vivo in the zebrafish–mouse melanoma xenograft model, showed much higher therapeutic potential than antiangiogenic drug sunitinib malate, while effectively blocking tumor neovascularization and melanoma cell metastasis. Overall therapeutic profile showed new dinuclear Pt(II) complexes could be novel, effective and safe anticancer agents. Finally, the correlation with the structural characteristics of these complexes can serve as a useful tool for developing new and more effective anticancer drugs.
PB  - Springer
T2  - Journal of Biological Inorganic Chemistry
T1  - New minor groove covering DNA binding mode of dinuclear Pt(II) complexes with various pyridine-linked bridging ligands and dual anticancer-antiangiogenic activities
VL  - 409
IS  - 25
SP  - 395
EP  - 409
DO  - 10.1007/s00775-020-01770-7
ER  - 

@article{
author = "Franich, Andjela and Živković, Marija D. and Ilić-Tomić, Tatjana and Đorđević, Ivana and Nikodinović-Runić, Jasmina and Pavić, Aleksandar and Janjić, Goran and Rajković, Snežana",
year = "2020",
abstract = "New anticancer platinum(II) compounds simultaneously targeting tumor cells and tumor-derived neoangiogenesis, with new DNA interacting mode and large therapeutic window are appealing alternative to improve efficacy of clinical platinum chemotherapeutics. Herein, we describe three novel dinuclear [{Pt(en)Cl}2(μ-L)]2+ complexes with different pyridine-like bridging ligands (L), 4,4′-bipyridine (Pt1), 1,2-bis(4-pyridyl)ethane (Pt2) and 1,2-bis(4-pyridyl)ethene (Pt3), which highly, positively charged aqua derivatives, [{Pt(en)(H2O)}2(μ-L)]4+, interact with the phosphate backbone forming DNA-Pt adducts with an unique and previously undescribed binding mode, called a minor groove covering. The results of this study suggested that the new binding mode of the aqua-Pt(II) complexes with DNA could be attributed to the higher anticancer activities of their chloride analogues. All three compounds, particularly complex [{Pt(en)Cl}2(μ-4,4′-bipy)]Cl2·2H2O (4,4′-bipy is 4,4′-bipyridine) (Pt1), overcame cisplatin resistance in vivo in the zebrafish–mouse melanoma xenograft model, showed much higher therapeutic potential than antiangiogenic drug sunitinib malate, while effectively blocking tumor neovascularization and melanoma cell metastasis. Overall therapeutic profile showed new dinuclear Pt(II) complexes could be novel, effective and safe anticancer agents. Finally, the correlation with the structural characteristics of these complexes can serve as a useful tool for developing new and more effective anticancer drugs.",
publisher = "Springer",
journal = "Journal of Biological Inorganic Chemistry",
title = "New minor groove covering DNA binding mode of dinuclear Pt(II) complexes with various pyridine-linked bridging ligands and dual anticancer-antiangiogenic activities",
volume = "409",
number = "25",
pages = "395-409",
doi = "10.1007/s00775-020-01770-7"
}

Franich, A., Živković, M. D., Ilić-Tomić, T., Đorđević, I., Nikodinović-Runić, J., Pavić, A., Janjić, G.,& Rajković, S.. (2020). New minor groove covering DNA binding mode of dinuclear Pt(II) complexes with various pyridine-linked bridging ligands and dual anticancer-antiangiogenic activities. in Journal of Biological Inorganic Chemistry
Springer., 409(25), 395-409.
https://doi.org/10.1007/s00775-020-01770-7

Franich A, Živković MD, Ilić-Tomić T, Đorđević I, Nikodinović-Runić J, Pavić A, Janjić G, Rajković S. New minor groove covering DNA binding mode of dinuclear Pt(II) complexes with various pyridine-linked bridging ligands and dual anticancer-antiangiogenic activities. in Journal of Biological Inorganic Chemistry. 2020;409(25):395-409.
doi:10.1007/s00775-020-01770-7 .

Franich, Andjela, Živković, Marija D., Ilić-Tomić, Tatjana, Đorđević, Ivana, Nikodinović-Runić, Jasmina, Pavić, Aleksandar, Janjić, Goran, Rajković, Snežana, "New minor groove covering DNA binding mode of dinuclear Pt(II) complexes with various pyridine-linked bridging ligands and dual anticancer-antiangiogenic activities" in Journal of Biological Inorganic Chemistry, 409, no. 25 (2020):395-409,
https://doi.org/10.1007/s00775-020-01770-7 . .