TY  - JOUR
AU  - Filipović, Nenad
AU  - Bjelogrlić, Snežana
AU  - Pelliccia, Sveva
AU  - Jovanović, Vesna B.
AU  - Kojić, Milan
AU  - Sencanski, Milan
AU  - La Regina, Giuseppe
AU  - Silvestri, Romano
AU  - Muller, Christian D.
AU  - Todorović, Tamara R.
PY  - 2020
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/5364
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 and Bjelogrlić, Snežana and Pelliccia, Sveva and Jovanović, Vesna B. and Kojić, 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., Bjelogrlić, S., Pelliccia, S., Jovanović, V. B., Kojić, 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 N, Bjelogrlić S, Pelliccia S, Jovanović VB, Kojić 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, Bjelogrlić, Snežana, Pelliccia, Sveva, Jovanović, Vesna B., Kojić, 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  - Isca, Vera M.S.
AU  - Sencanski, Milan
AU  - Filipović, Nenad
AU  - Dos Santos, Daniel J.V.A.
AU  - Cipak-Gasparović, Ana
AU  - Saraiva, Lucilia
AU  - Afonso, Carlos A.M.
AU  - Rijo, Patricia
AU  - Garcia-Sosa, Alfonso T.
PY  - 2020
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/5386
AB  - Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7 alpha -acetoxy-6 beta -hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones' bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr(2) (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes.
PB  - MDPI, BASEL
T2  - International Journal of Molecular Sciences
T1  - Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones
IS  - 10
VL  - 21
DO  - 10.3390/ijms21103671
ER  - 

@article{
author = "Isca, Vera M.S. and Sencanski, Milan and Filipović, Nenad and Dos Santos, Daniel J.V.A. and Cipak-Gasparović, Ana and Saraiva, Lucilia and Afonso, Carlos A.M. and Rijo, Patricia and Garcia-Sosa, Alfonso T.",
year = "2020",
abstract = "Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7 alpha -acetoxy-6 beta -hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones' bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr(2) (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes.",
publisher = "MDPI, BASEL",
journal = "International Journal of Molecular Sciences",
title = "Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones",
number = "10",
volume = "21",
doi = "10.3390/ijms21103671"
}

Isca, V. M.S., Sencanski, M., Filipović, N., Dos Santos, D. J.V.A., Cipak-Gasparović, A., Saraiva, L., Afonso, C. A.M., Rijo, P.,& Garcia-Sosa, A. T.. (2020). Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones. in International Journal of Molecular Sciences
MDPI, BASEL., 21(10).
https://doi.org/10.3390/ijms21103671

Isca VM, Sencanski M, Filipović N, Dos Santos DJ, Cipak-Gasparović A, Saraiva L, Afonso CA, Rijo P, Garcia-Sosa AT. Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones. in International Journal of Molecular Sciences. 2020;21(10).
doi:10.3390/ijms21103671 .

Isca, Vera M.S., Sencanski, Milan, Filipović, Nenad, Dos Santos, Daniel J.V.A., Cipak-Gasparović, Ana, Saraiva, Lucilia, Afonso, Carlos A.M., Rijo, Patricia, Garcia-Sosa, Alfonso T., "Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones" in International Journal of Molecular Sciences, 21, no. 10 (2020),
https://doi.org/10.3390/ijms21103671 . .

TY  - JOUR
AU  - Bjelogrlić, Snežana
AU  - Todorović, Tamara R.
AU  - Kojić, Milan
AU  - Sencanski, Milan
AU  - Nikolić, Milan
AU  - Visnjevac, Aleksandar
AU  - Araskov, Jovana
AU  - Miljković, Marija
AU  - Muller, Christian D.
AU  - Filipović, Nenad
PY  - 2019
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/4916
AB  - Anticancer activity of Pd complexes 1-5 with bidentate N-heteroaromatic hydrazone ligands was investigated on human acute monocytic leukemia (THP-1; cells in a suspension) and human mammary adenocarcinoma (MCF-7; two-dimensional layer and three-dimensional spheroid tumor model) cell lines. For the Pd(II) complexes with condensation products of ethyl hydrazainoacetate and quinoline-8-carboxaldehyde (complex 1) and 2-for-mylpyridine (complex 3), for which apoptosis was determined as a mechanism of anticancer activity, further investigation revealed that they arrest the cell cycle in G0/G1 phase, induce generation of reactive oxygen species and inhibit Topoisomerase I in vitro. In silico studies corroborate experimental findings that these complexes show topoisomerase inhibition activity in the micromolar range and indicate binding to a DNA's minor groove as another potential target. Based on the results obtained by circular dichroism and fluorescence spectroscopy measurements, the most active complexes are suitable to be delivered to a blood stream via human serum albumin.
PB  - Elsevier Science Inc, New York
T2  - Journal of Inorganic Biochemistry
T1  - Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification
VL  - 199
DO  - 10.1016/j.jinorgbio.2019.110758
ER  - 

@article{
author = "Bjelogrlić, Snežana and Todorović, Tamara R. and Kojić, Milan and Sencanski, Milan and Nikolić, Milan and Visnjevac, Aleksandar and Araskov, Jovana and Miljković, Marija and Muller, Christian D. and Filipović, Nenad",
year = "2019",
abstract = "Anticancer activity of Pd complexes 1-5 with bidentate N-heteroaromatic hydrazone ligands was investigated on human acute monocytic leukemia (THP-1; cells in a suspension) and human mammary adenocarcinoma (MCF-7; two-dimensional layer and three-dimensional spheroid tumor model) cell lines. For the Pd(II) complexes with condensation products of ethyl hydrazainoacetate and quinoline-8-carboxaldehyde (complex 1) and 2-for-mylpyridine (complex 3), for which apoptosis was determined as a mechanism of anticancer activity, further investigation revealed that they arrest the cell cycle in G0/G1 phase, induce generation of reactive oxygen species and inhibit Topoisomerase I in vitro. In silico studies corroborate experimental findings that these complexes show topoisomerase inhibition activity in the micromolar range and indicate binding to a DNA's minor groove as another potential target. Based on the results obtained by circular dichroism and fluorescence spectroscopy measurements, the most active complexes are suitable to be delivered to a blood stream via human serum albumin.",
publisher = "Elsevier Science Inc, New York",
journal = "Journal of Inorganic Biochemistry",
title = "Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification",
volume = "199",
doi = "10.1016/j.jinorgbio.2019.110758"
}

Bjelogrlić, S., Todorović, T. R., Kojić, M., Sencanski, M., Nikolić, M., Visnjevac, A., Araskov, J., Miljković, M., Muller, C. D.,& Filipović, N.. (2019). Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification. in Journal of Inorganic Biochemistry
Elsevier Science Inc, New York., 199.
https://doi.org/10.1016/j.jinorgbio.2019.110758

Bjelogrlić S, Todorović TR, Kojić M, Sencanski M, Nikolić M, Visnjevac A, Araskov J, Miljković M, Muller CD, Filipović N. Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification. in Journal of Inorganic Biochemistry. 2019;199.
doi:10.1016/j.jinorgbio.2019.110758 .

Bjelogrlić, Snežana, Todorović, Tamara R., Kojić, Milan, Sencanski, Milan, Nikolić, Milan, Visnjevac, Aleksandar, Araskov, Jovana, Miljković, Marija, Muller, Christian D., Filipović, Nenad, "Pd(II) complexes with N-heteroaromatic hydrazone ligands: Anticancer activity, in silico and experimental target identification" in Journal of Inorganic Biochemistry, 199 (2019),
https://doi.org/10.1016/j.jinorgbio.2019.110758 . .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Bjelogrlić, Snežana
AU  - Portalone, Gustavo
AU  - Pelliccia, Sveva
AU  - Silvestri, Romano
AU  - Klisurić, Olivera
AU  - Sencanski, Milan
AU  - Stanković, Dalibor
AU  - Todorović, Tamara R.
AU  - Muller, Christian D.
PY  - 2016
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/4028
AB  - 8-Quinolinecarboxaldehyde selenosemicarbazone (H8qasesc) and its octahedral Co(III) complex were characterized by single crystal X-ray diffraction analysis, spectroscopy methods and cyclic voltammetry. The antineoplastic activity of the ligand and the complex has been assessed on an acute monocytic leukemia cell line (THP-1) and AsPC-1 cancer stem cell (CSC) line derived from a patient suffering from pancreatic adenocarcinoma, with cisplatin (CDDP) as a reference compound. Evaluation involved determination of pro-apoptotic activity, changes in cell cycle distribution, the role of caspase activation in the process of cell death, and the ability of the investigated compounds to challenge reprogramming of the CSC phenotype. Compared to CDDP, treatment with H8qasesc induced a higher apoptotic response in both investigated cell lines. Apoptosis triggered by H8qasesc was highly caspase-dependent but did not include activation of either caspase-8 or -9. According to cell cycle changes H8qasesc delayed the transition of cells during DNA replication but in a manner different from that of CDDP. The ligand did not show nuclease activity on pUC19 plasmid, while docking studies disclosed that it does not have intercalating properties. Treatment of THP-1 cells with the Co(III) complex resulted in a strong toxic response, whereas cell death in the treated AsPC-1 line was not achieved for 24 h. Additionally, the complex concentration-dependently digested plasmid DNA which might be the cause of its cytotoxic activity. Finally, H8qasesc successfully initiated reprogramming of the CSC phenotype in the AsPC-1 cell line.
PB  - Royal Soc Chemistry, Cambridge
T2  - Medchemcomm
T1  - Pro-apoptotic and pro-differentiation induction by 8-quinolinecarboxaldehyde selenosemicarbazone and its Co(III) complex in human cancer cell lines
EP  - 1616
IS  - 8
SP  - 1604
VL  - 7
DO  - 10.1039/c6md00199h
ER  - 

@article{
author = "Filipović, Nenad and Bjelogrlić, Snežana and Portalone, Gustavo and Pelliccia, Sveva and Silvestri, Romano and Klisurić, Olivera and Sencanski, Milan and Stanković, Dalibor and Todorović, Tamara R. and Muller, Christian D.",
year = "2016",
abstract = "8-Quinolinecarboxaldehyde selenosemicarbazone (H8qasesc) and its octahedral Co(III) complex were characterized by single crystal X-ray diffraction analysis, spectroscopy methods and cyclic voltammetry. The antineoplastic activity of the ligand and the complex has been assessed on an acute monocytic leukemia cell line (THP-1) and AsPC-1 cancer stem cell (CSC) line derived from a patient suffering from pancreatic adenocarcinoma, with cisplatin (CDDP) as a reference compound. Evaluation involved determination of pro-apoptotic activity, changes in cell cycle distribution, the role of caspase activation in the process of cell death, and the ability of the investigated compounds to challenge reprogramming of the CSC phenotype. Compared to CDDP, treatment with H8qasesc induced a higher apoptotic response in both investigated cell lines. Apoptosis triggered by H8qasesc was highly caspase-dependent but did not include activation of either caspase-8 or -9. According to cell cycle changes H8qasesc delayed the transition of cells during DNA replication but in a manner different from that of CDDP. The ligand did not show nuclease activity on pUC19 plasmid, while docking studies disclosed that it does not have intercalating properties. Treatment of THP-1 cells with the Co(III) complex resulted in a strong toxic response, whereas cell death in the treated AsPC-1 line was not achieved for 24 h. Additionally, the complex concentration-dependently digested plasmid DNA which might be the cause of its cytotoxic activity. Finally, H8qasesc successfully initiated reprogramming of the CSC phenotype in the AsPC-1 cell line.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Medchemcomm",
title = "Pro-apoptotic and pro-differentiation induction by 8-quinolinecarboxaldehyde selenosemicarbazone and its Co(III) complex in human cancer cell lines",
pages = "1616-1604",
number = "8",
volume = "7",
doi = "10.1039/c6md00199h"
}

Filipović, N., Bjelogrlić, S., Portalone, G., Pelliccia, S., Silvestri, R., Klisurić, O., Sencanski, M., Stanković, D., Todorović, T. R.,& Muller, C. D.. (2016). Pro-apoptotic and pro-differentiation induction by 8-quinolinecarboxaldehyde selenosemicarbazone and its Co(III) complex in human cancer cell lines. in Medchemcomm
Royal Soc Chemistry, Cambridge., 7(8), 1604-1616.
https://doi.org/10.1039/c6md00199h

Filipović N, Bjelogrlić S, Portalone G, Pelliccia S, Silvestri R, Klisurić O, Sencanski M, Stanković D, Todorović TR, Muller CD. Pro-apoptotic and pro-differentiation induction by 8-quinolinecarboxaldehyde selenosemicarbazone and its Co(III) complex in human cancer cell lines. in Medchemcomm. 2016;7(8):1604-1616.
doi:10.1039/c6md00199h .

Filipović, Nenad, Bjelogrlić, Snežana, Portalone, Gustavo, Pelliccia, Sveva, Silvestri, Romano, Klisurić, Olivera, Sencanski, Milan, Stanković, Dalibor, Todorović, Tamara R., Muller, Christian D., "Pro-apoptotic and pro-differentiation induction by 8-quinolinecarboxaldehyde selenosemicarbazone and its Co(III) complex in human cancer cell lines" in Medchemcomm, 7, no. 8 (2016):1604-1616,
https://doi.org/10.1039/c6md00199h . .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Bjelogrlić, Snežana
AU  - Todorović, Tamara R.
AU  - Blagojević, Vladimir A.
AU  - Muller, Christian D.
AU  - Marinković, Aleksandar
AU  - Vujcić, Miroslava
AU  - Janović, Barbara
AU  - Malesević, Aleksandar
AU  - Begović, Nebojša
AU  - Sencanski, Milan
AU  - Minić, Dragica M.
PY  - 2016
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/4060
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 and Bjelogrlić, Snežana and Todorović, Tamara R. and Blagojević, Vladimir A. and Muller, Christian D. and Marinković, Aleksandar and Vujcić, Miroslava and Janović, Barbara and Malesević, Aleksandar and Begović, Nebojša and Sencanski, Milan and Minić, Dragica M.",
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., Bjelogrlić, S., Todorović, T. R., Blagojević, V. A., Muller, C. D., Marinković, A., Vujcić, M., Janović, B., Malesević, A., Begović, N., Sencanski, M.,& Minić, D. M.. (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 N, Bjelogrlić S, Todorović TR, Blagojević VA, Muller CD, Marinković A, Vujcić M, Janović B, Malesević A, Begović N, Sencanski M, Minić DM. 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, Bjelogrlić, Snežana, Todorović, Tamara R., Blagojević, Vladimir A., Muller, Christian D., Marinković, Aleksandar, Vujcić, Miroslava, Janović, Barbara, Malesević, Aleksandar, Begović, Nebojša, Sencanski, Milan, Minić, Dragica M., "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 . .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Bjelogrlić, Snežana
AU  - Marinković, Aleksandar
AU  - Verbić, Tatjana Z.
AU  - Cvijetić, Ilija N.
AU  - Sencanski, Milan
AU  - Rodić, Marko
AU  - Vujcić, Miroslava
AU  - Sladić, Dušan M.
AU  - Striković, Zlatko
AU  - Todorović, Tamara R.
AU  - Muller, Christian D.
PY  - 2015
UR  - http://aspace.agrif.bg.ac.rs/handle/123456789/3749
AB  - A new Zn(II)-based potential chemotherapeutic agent was synthesized from the ligand 2-quinolinecarboxaldehyde selenosemicarbazone (Hqasesc). Single crystal X-ray diffraction analysis showed that the Zn(II) complex consists of a cation [Zn(Hqasesc)(2)](2+), two perchlorate anions and one ethanol solvent molecule. The interaction of calf thymus (CT) DNA and human serum albumin (HSA) with the Zn(II) complex was explored using absorption and emission spectral methods, and also has been supported by molecular docking studies. The complex has more affinity to minor DNA groove than major, with no significant intercalation. The HSA interaction studies of the complex revealed the quenching of the intrinsic fluorescence of the HSA through a static quenching mechanism. The antitumor activity of the ligand and the complex against pancreatic adenocarcinoma cell line (AsPC-1) and acute monocytic leukemia (THP-1) cells was evaluated. Both compounds are strong concentration-dependent apoptosis inducers in THP-1 cells. While Hqasesc in AsPC-1 cells induces apoptosis only at the highest concentration, treatment with the Zn complex shows a concentration-dependent apoptotic response, where the treated cells are arrested in the G1-to-S phase accompanied with extensive activation of caspase-8 and -9. These results indicate that the ligand and Zn(II) complex display cell phenotype specific activity.
PB  - Royal Soc Chemistry, Cambridge
T2  - RSC Advances
T1  - Zn(II) complex with 2-quinolinecarboxaldehyde selenosemicarbazone: synthesis, structure, interaction studies with DNA/HSA, molecular docking and caspase-8 and-9 independent apoptose induction
EP  - 95211
IS  - 115
SP  - 95191
VL  - 5
DO  - 10.1039/c5ra19849f
ER  - 

@article{
author = "Filipović, Nenad and Bjelogrlić, Snežana and Marinković, Aleksandar and Verbić, Tatjana Z. and Cvijetić, Ilija N. and Sencanski, Milan and Rodić, Marko and Vujcić, Miroslava and Sladić, Dušan M. and Striković, Zlatko and Todorović, Tamara R. and Muller, Christian D.",
year = "2015",
abstract = "A new Zn(II)-based potential chemotherapeutic agent was synthesized from the ligand 2-quinolinecarboxaldehyde selenosemicarbazone (Hqasesc). Single crystal X-ray diffraction analysis showed that the Zn(II) complex consists of a cation [Zn(Hqasesc)(2)](2+), two perchlorate anions and one ethanol solvent molecule. The interaction of calf thymus (CT) DNA and human serum albumin (HSA) with the Zn(II) complex was explored using absorption and emission spectral methods, and also has been supported by molecular docking studies. The complex has more affinity to minor DNA groove than major, with no significant intercalation. The HSA interaction studies of the complex revealed the quenching of the intrinsic fluorescence of the HSA through a static quenching mechanism. The antitumor activity of the ligand and the complex against pancreatic adenocarcinoma cell line (AsPC-1) and acute monocytic leukemia (THP-1) cells was evaluated. Both compounds are strong concentration-dependent apoptosis inducers in THP-1 cells. While Hqasesc in AsPC-1 cells induces apoptosis only at the highest concentration, treatment with the Zn complex shows a concentration-dependent apoptotic response, where the treated cells are arrested in the G1-to-S phase accompanied with extensive activation of caspase-8 and -9. These results indicate that the ligand and Zn(II) complex display cell phenotype specific activity.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "RSC Advances",
title = "Zn(II) complex with 2-quinolinecarboxaldehyde selenosemicarbazone: synthesis, structure, interaction studies with DNA/HSA, molecular docking and caspase-8 and-9 independent apoptose induction",
pages = "95211-95191",
number = "115",
volume = "5",
doi = "10.1039/c5ra19849f"
}

Filipović, N., Bjelogrlić, S., Marinković, A., Verbić, T. Z., Cvijetić, I. N., Sencanski, M., Rodić, M., Vujcić, M., Sladić, D. M., Striković, Z., Todorović, T. R.,& Muller, C. D.. (2015). Zn(II) complex with 2-quinolinecarboxaldehyde selenosemicarbazone: synthesis, structure, interaction studies with DNA/HSA, molecular docking and caspase-8 and-9 independent apoptose induction. in RSC Advances
Royal Soc Chemistry, Cambridge., 5(115), 95191-95211.
https://doi.org/10.1039/c5ra19849f

Filipović N, Bjelogrlić S, Marinković A, Verbić TZ, Cvijetić IN, Sencanski M, Rodić M, Vujcić M, Sladić DM, Striković Z, Todorović TR, Muller CD. Zn(II) complex with 2-quinolinecarboxaldehyde selenosemicarbazone: synthesis, structure, interaction studies with DNA/HSA, molecular docking and caspase-8 and-9 independent apoptose induction. in RSC Advances. 2015;5(115):95191-95211.
doi:10.1039/c5ra19849f .

Filipović, Nenad, Bjelogrlić, Snežana, Marinković, Aleksandar, Verbić, Tatjana Z., Cvijetić, Ilija N., Sencanski, Milan, Rodić, Marko, Vujcić, Miroslava, Sladić, Dušan M., Striković, Zlatko, Todorović, Tamara R., Muller, Christian D., "Zn(II) complex with 2-quinolinecarboxaldehyde selenosemicarbazone: synthesis, structure, interaction studies with DNA/HSA, molecular docking and caspase-8 and-9 independent apoptose induction" in RSC Advances, 5, no. 115 (2015):95191-95211,
https://doi.org/10.1039/c5ra19849f . .