TY  - JOUR
AU  - Franich, Andjela A.
AU  - Živković, Marija D.
AU  - Ilić-Tomić, Tatjana
AU  - Đorđević, Ivana S.
AU  - Nikodinović-Runić, Jasmina
AU  - Pavić, Aleksandar
AU  - Janjić, Goran V.
AU  - Rajković, Snežana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1400
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)(mu-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)(mu-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)(mu-4,4 '-bipy)]Cl-2 center dot 2H(2)O (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, New York
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
EP  - 409
IS  - 3
SP  - 395
VL  - 25
DO  - 10.1007/s00775-020-01770-7
ER  - 

@article{
author = "Franich, Andjela A. and Živković, Marija D. and Ilić-Tomić, Tatjana and Đorđević, Ivana S. and Nikodinović-Runić, Jasmina and Pavić, Aleksandar and Janjić, Goran V. 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)(mu-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)(mu-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)(mu-4,4 '-bipy)]Cl-2 center dot 2H(2)O (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, New York",
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",
pages = "409-395",
number = "3",
volume = "25",
doi = "10.1007/s00775-020-01770-7"
}

Franich, A. A., Živković, M. D., Ilić-Tomić, T., Đorđević, I. S., Nikodinović-Runić, J., Pavić, A., Janjić, G. V.,& 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, New York., 25(3), 395-409.
https://doi.org/10.1007/s00775-020-01770-7

Franich AA, Živković MD, Ilić-Tomić T, Đorđević IS, Nikodinović-Runić J, Pavić A, Janjić GV, 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;25(3):395-409.
doi:10.1007/s00775-020-01770-7 .

Franich, Andjela A., Živković, Marija D., Ilić-Tomić, Tatjana, Đorđević, Ivana S., Nikodinović-Runić, Jasmina, Pavić, Aleksandar, Janjić, Goran V., 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, 25, no. 3 (2020):395-409,
https://doi.org/10.1007/s00775-020-01770-7 . .

TY  - JOUR
AU  - Pavić, Aleksandar
AU  - Glišić, Biljana
AU  - Vojnović, Sandra
AU  - Warzajtis, Beata
AU  - Savić, Nada D.
AU  - Antić, Marija
AU  - Radenković, Slavko
AU  - Janjić, Goran V.
AU  - Nikodinović-Runić, Jasmina
AU  - Rychlewska, Urszula
AU  - Djuran, Milos I.
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1756
AB  - Gold(III) complexes with 1,7- and 4,7-phenanthroline ligands, [AuCl3(1,7-phen-kappa N7)] (1) and [AuCl3(4,7-phen-kappa N4)] (2) were synthesized and structurally characterized by spectroscopic (NMR, IR and UV-vis) and single crystal X-ray diffraction techniques. In these complexes, 1,7- and 4,7-phenanthrolines are monodentatedly coordinated to the Au(III) ion through the N7 and N4 nitrogen atoms, respectively. In comparison to the clinically relevant anti-angiogenic compounds auranofin and sunitinib, gold(III)-phenanthroline complexes showed from 1.5- to 20-fold higher anti-angiogenic potential, and 13- and 118-fold lower toxicity. Among the tested compounds, complex 1 was the most potent and may be an excellent anti-angiogenic drug candidate, since it showed strong anti-angiogenic activity in zebrafish embryos achieving IC50 value (concentration resulting in an anti-angiogenic phenotype at 50% of embryos) of 2.89 mu M, while had low toxicity with LC50 value (the concentration inducing the lethal effect of 50% embryos) of 128 mu M. Molecular docking study revealed that both complexes and ligands could suppress angiogenesis targeting the multiple major regulators of angiogenesis, such as the vascular endothelial growth factor receptor (VEGFR-2), the matrix metalloproteases (MMP-2 and MMP-9), and thioredoxin reductase (TrxR1), where the complexes showed higher binding affinity in comparison to ligands, and particularly to auranofin, but comparable to sunitinib, an anti-angiogenic drug of clinical relevance.
PB  - Elsevier Science Inc, New York
T2  - Journal of Inorganic Biochemistry
T1  - Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib
EP  - 168
SP  - 156
VL  - 174
DO  - 10.1016/j.jinorgbio.2017.06.009
ER  - 

@article{
author = "Pavić, Aleksandar and Glišić, Biljana and Vojnović, Sandra and Warzajtis, Beata and Savić, Nada D. and Antić, Marija and Radenković, Slavko and Janjić, Goran V. and Nikodinović-Runić, Jasmina and Rychlewska, Urszula and Djuran, Milos I.",
year = "2017",
abstract = "Gold(III) complexes with 1,7- and 4,7-phenanthroline ligands, [AuCl3(1,7-phen-kappa N7)] (1) and [AuCl3(4,7-phen-kappa N4)] (2) were synthesized and structurally characterized by spectroscopic (NMR, IR and UV-vis) and single crystal X-ray diffraction techniques. In these complexes, 1,7- and 4,7-phenanthrolines are monodentatedly coordinated to the Au(III) ion through the N7 and N4 nitrogen atoms, respectively. In comparison to the clinically relevant anti-angiogenic compounds auranofin and sunitinib, gold(III)-phenanthroline complexes showed from 1.5- to 20-fold higher anti-angiogenic potential, and 13- and 118-fold lower toxicity. Among the tested compounds, complex 1 was the most potent and may be an excellent anti-angiogenic drug candidate, since it showed strong anti-angiogenic activity in zebrafish embryos achieving IC50 value (concentration resulting in an anti-angiogenic phenotype at 50% of embryos) of 2.89 mu M, while had low toxicity with LC50 value (the concentration inducing the lethal effect of 50% embryos) of 128 mu M. Molecular docking study revealed that both complexes and ligands could suppress angiogenesis targeting the multiple major regulators of angiogenesis, such as the vascular endothelial growth factor receptor (VEGFR-2), the matrix metalloproteases (MMP-2 and MMP-9), and thioredoxin reductase (TrxR1), where the complexes showed higher binding affinity in comparison to ligands, and particularly to auranofin, but comparable to sunitinib, an anti-angiogenic drug of clinical relevance.",
publisher = "Elsevier Science Inc, New York",
journal = "Journal of Inorganic Biochemistry",
title = "Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib",
pages = "168-156",
volume = "174",
doi = "10.1016/j.jinorgbio.2017.06.009"
}

Pavić, A., Glišić, B., Vojnović, S., Warzajtis, B., Savić, N. D., Antić, M., Radenković, S., Janjić, G. V., Nikodinović-Runić, J., Rychlewska, U.,& Djuran, M. I.. (2017). Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib. in Journal of Inorganic Biochemistry
Elsevier Science Inc, New York., 174, 156-168.
https://doi.org/10.1016/j.jinorgbio.2017.06.009

Pavić A, Glišić B, Vojnović S, Warzajtis B, Savić ND, Antić M, Radenković S, Janjić GV, Nikodinović-Runić J, Rychlewska U, Djuran MI. Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib. in Journal of Inorganic Biochemistry. 2017;174:156-168.
doi:10.1016/j.jinorgbio.2017.06.009 .

Pavić, Aleksandar, Glišić, Biljana, Vojnović, Sandra, Warzajtis, Beata, Savić, Nada D., Antić, Marija, Radenković, Slavko, Janjić, Goran V., Nikodinović-Runić, Jasmina, Rychlewska, Urszula, Djuran, Milos I., "Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib" in Journal of Inorganic Biochemistry, 174 (2017):156-168,
https://doi.org/10.1016/j.jinorgbio.2017.06.009 . .