TY  - JOUR
AU  - Filipović, Nenad R.
AU  - Bjelogrlic, Snežana
AU  - Pelliccia, Sveva
AU  - Jovanović, Vesna B.
AU  - Kojic, Milan
AU  - Sencanski, Milan
AU  - La Regina, Giuseppe
AU  - Silvestri, Romano
AU  - Muller, Christian D.
AU  - Todorović, Tamara R.
PY  - 2020
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1295
AB  - Triapine, the most studied alpha-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay.
PB  - Elsevier, Amsterdam
T2  - Arabian Journal of Chemistry
T1  - Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors
EP  - 1489
IS  - 1
SP  - 1466
VL  - 13
DO  - 10.1016/j.arabjc.2017.11.017
ER  - 

@article{
author = "Filipović, Nenad R. and Bjelogrlic, Snežana and Pelliccia, Sveva and Jovanović, Vesna B. and Kojic, Milan and Sencanski, Milan and La Regina, Giuseppe and Silvestri, Romano and Muller, Christian D. and Todorović, Tamara R.",
year = "2020",
abstract = "Triapine, the most studied alpha-N-heterocyclic thiosemicarbazone, revealed potent activity against advanced leukemia, but was ineffective against a variety of solid tumors. Moreover, methemoglobinemia, which is a side effect of triapine administration, may limits all clinical application. To enhance anticancer activity and reduce side effects, we applied an isosteric replacement of sulfur to selenium atom was performed by synthesis and characterization of selenium triapine analog, 3-aminopyridine-2-carboxaldehyde selenosemicarbazone (selenotriapine). Compared to triapine, selenotriapine revealed superior pro-apoptotic activity with activation of intrinsic apoptotic pathway in both human monocytic leukemia (THP-1) and mammary adenocarcinoma (MCF-7) cell lines. For MCF-7 2-D cultures, selenotriapine induced notable increase in mitochondrial superoxide radical generation and dissipation of mitochondrial transmembrane potential. A significant delay in growth of MCF-7 spheroids (3-D culture) was accompanied by phenotypic stem cell reprogramming (Oct-4 expression). Additionally, selenotriapine demonstrated a very low toxicity profile as compared to triapine, confirmed over alleviated extent of methemoglobin formation and higher IC50 value in brine shrimp cytotoxicity assay.",
publisher = "Elsevier, Amsterdam",
journal = "Arabian Journal of Chemistry",
title = "Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors",
pages = "1489-1466",
number = "1",
volume = "13",
doi = "10.1016/j.arabjc.2017.11.017"
}

Filipović, N. R., Bjelogrlic, S., Pelliccia, S., Jovanović, V. B., Kojic, M., Sencanski, M., La Regina, G., Silvestri, R., Muller, C. D.,& Todorović, T. R.. (2020). Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors. in Arabian Journal of Chemistry
Elsevier, Amsterdam., 13(1), 1466-1489.
https://doi.org/10.1016/j.arabjc.2017.11.017

Filipović NR, Bjelogrlic S, Pelliccia S, Jovanović VB, Kojic M, Sencanski M, La Regina G, Silvestri R, Muller CD, Todorović TR. Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors. in Arabian Journal of Chemistry. 2020;13(1):1466-1489.
doi:10.1016/j.arabjc.2017.11.017 .

Filipović, Nenad R., Bjelogrlic, Snežana, Pelliccia, Sveva, Jovanović, Vesna B., Kojic, Milan, Sencanski, Milan, La Regina, Giuseppe, Silvestri, Romano, Muller, Christian D., Todorović, Tamara R., "Selenotriapine - An isostere of the most studied thiosemicarbazone with pronounced pro-apoptotic activity, low toxicity and ability to challenge phenotype reprogramming of 3-D mammary adenocarcinoma tumors" in Arabian Journal of Chemistry, 13, no. 1 (2020):1466-1489,
https://doi.org/10.1016/j.arabjc.2017.11.017 . .

TY  - JOUR
AU  - Filipović, Nenad R.
AU  - Bjelogrlic, Snežana
AU  - Todorović, Tamara R.
AU  - Blagojević, Vladimir A.
AU  - Muller, Christian D.
AU  - Marinković, Aleksandar
AU  - Vujcic, Miroslava
AU  - Janović, Barbara
AU  - Malešević, Aleksandar
AU  - Begović, Nebojša
AU  - Sencanski, Milan
AU  - Minic, Dragica
PY  - 2016
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/972
AB  - A new Ni(II) complex, [Ni(L)(H2O)] (1), with diethyl 3,3'-(2,2'-(1,1'-(pyridine-2,6-diyl) bis(ethan-1-yl-1-ylidene)) bis(hydrazin-1-yl-2-ylidene)) bis(3-oxopropanoate) ligand (H2L) was synthesized as a potential chemotherapeutic agent. Polidentate ligand was coordinated to Ni(II) NNN-tridentately, in dianionic form, while monodentate water coordination completed square-planar geometry around metal. Structure in the solution was determined by NMR spectroscopy and the same coordination mode was observed in the solid state using IR spectroscopy and further verified by DFT calculations and electrochemical studies. Thermal stability of 1 was determined in both air and nitrogen atmosphere. Anticancer activity of 1 was investigated on acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma (AsPC-1) cell lines. On THP-1 cells 1 induced powerful apoptotic response (ED50 = 10 +/- 3 mu M), which was revealed to be only partially caspase-dependent, with activation of caspase-8 as the dominant course. This suggested that experimentally validated covalent binding of 1 to DNA is not the only mechanism responsible for programmed cell death. This was supported with experiments on AsPC-1 cells. Although treatment of those cells with 1 resulted in poor apoptotic response, cell cycle changes showed concentration-dependent shifts indicating a dual mechanism of activity. This study also reviews the results of preliminary biological screening, which demonstrates that 1 displays a unique pattern of anticancer activity with at least two mechanisms involved.
PB  - Royal Soc Chemistry, Cambridge
T2  - RSC Advances
T1  - Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines
EP  - 108740
IS  - 110
SP  - 108726
VL  - 6
DO  - 10.1039/c6ra24604d
ER  - 

@article{
author = "Filipović, Nenad R. and Bjelogrlic, Snežana and Todorović, Tamara R. and Blagojević, Vladimir A. and Muller, Christian D. and Marinković, Aleksandar and Vujcic, Miroslava and Janović, Barbara and Malešević, Aleksandar and Begović, Nebojša and Sencanski, Milan and Minic, Dragica",
year = "2016",
abstract = "A new Ni(II) complex, [Ni(L)(H2O)] (1), with diethyl 3,3'-(2,2'-(1,1'-(pyridine-2,6-diyl) bis(ethan-1-yl-1-ylidene)) bis(hydrazin-1-yl-2-ylidene)) bis(3-oxopropanoate) ligand (H2L) was synthesized as a potential chemotherapeutic agent. Polidentate ligand was coordinated to Ni(II) NNN-tridentately, in dianionic form, while monodentate water coordination completed square-planar geometry around metal. Structure in the solution was determined by NMR spectroscopy and the same coordination mode was observed in the solid state using IR spectroscopy and further verified by DFT calculations and electrochemical studies. Thermal stability of 1 was determined in both air and nitrogen atmosphere. Anticancer activity of 1 was investigated on acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma (AsPC-1) cell lines. On THP-1 cells 1 induced powerful apoptotic response (ED50 = 10 +/- 3 mu M), which was revealed to be only partially caspase-dependent, with activation of caspase-8 as the dominant course. This suggested that experimentally validated covalent binding of 1 to DNA is not the only mechanism responsible for programmed cell death. This was supported with experiments on AsPC-1 cells. Although treatment of those cells with 1 resulted in poor apoptotic response, cell cycle changes showed concentration-dependent shifts indicating a dual mechanism of activity. This study also reviews the results of preliminary biological screening, which demonstrates that 1 displays a unique pattern of anticancer activity with at least two mechanisms involved.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "RSC Advances",
title = "Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines",
pages = "108740-108726",
number = "110",
volume = "6",
doi = "10.1039/c6ra24604d"
}

Filipović, N. R., Bjelogrlic, S., Todorović, T. R., Blagojević, V. A., Muller, C. D., Marinković, A., Vujcic, M., Janović, B., Malešević, A., Begović, N., Sencanski, M.,& Minic, D.. (2016). Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines. in RSC Advances
Royal Soc Chemistry, Cambridge., 6(110), 108726-108740.
https://doi.org/10.1039/c6ra24604d

Filipović NR, Bjelogrlic S, Todorović TR, Blagojević VA, Muller CD, Marinković A, Vujcic M, Janović B, Malešević A, Begović N, Sencanski M, Minic D. Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines. in RSC Advances. 2016;6(110):108726-108740.
doi:10.1039/c6ra24604d .

Filipović, Nenad R., Bjelogrlic, Snežana, Todorović, Tamara R., Blagojević, Vladimir A., Muller, Christian D., Marinković, Aleksandar, Vujcic, Miroslava, Janović, Barbara, Malešević, Aleksandar, Begović, Nebojša, Sencanski, Milan, Minic, Dragica, "Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines" in RSC Advances, 6, no. 110 (2016):108726-108740,
https://doi.org/10.1039/c6ra24604d . .