TY  - JOUR
AU  - Misirlić-Denčić, Sonja
AU  - Poljarević, Jelena
AU  - Isaković, Anđelka M.
AU  - Sabo, Tibor
AU  - Marković, Ivanka
AU  - Trajković, Vladimir S.
PY  - 2020
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5072
AB  - Background: The discovery of cisplatin and the subsequent research revealed the importance of dinitrogen-containing moiety for the anticancer action of metal complexes. Moreover, certain diamine ligands alone display cytotoxicity that contributes to the overall activity of corresponding complexes.

Objective: To summarize the current knowledge on the anticancer efficacy, selectivity, and the mechanisms of action of metal complexes with various types of diamine ligands.

Methods: The contribution of aliphatic acyclic, aliphatic cyclic, and aromatic diamine ligands to the anticancer activity and selectivity/toxicity of metal complexes with different metal ions were analyzed by comparison with organic ligand alone and/or conventional platinum-based chemotherapeutics.

Results: The aliphatic acyclic diamine ligands are present mostly in complexes with platinum. Aliphatic cyclic diamines are part of Pt(II), Ru(II) and Au(III) complexes, while aromatic diamine ligands are found in Pt(II), Ru(II), Pd(II) and Ir(III) complexes. The type and oxidation state of metal ions greatly influences the cytotoxicity of metal complexes with aliphatic acyclic diamine ligands. Lipophilicity of organic ligands, dependent on alkyl-side chain length and structure, determines their cellular uptake, with edda and eddp/eddip ligands being most useful in this regard. Aliphatic cyclic diamine ligands improved the activity/toxicity ratio of oxaliplatin-type complexes. The complexes with aromatic diamine ligands remain unexplored regarding their anticancer mechanism. The investigated complexes mainly caused apoptotic or necrotic cell death.

Conclusion: Metal complexes with diamine ligands are promising candidates for efficient and more selective alternatives to conventional platinum-based chemotherapeutics. Further research is required to reveal the chemico-physical properties and molecular mechanisms underlying their biological activity.
PB  - Bentham Science
T2  - Current Medicinal Chemistry
T1  - Current development of metal complexes with diamine ligands as potential anticancer agents
VL  - 27
IS  - 3
SP  - 380
EP  - 410
DO  - 10.2174/0929867325666181031114306
ER  - 

@article{
author = "Misirlić-Denčić, Sonja and Poljarević, Jelena and Isaković, Anđelka M. and Sabo, Tibor and Marković, Ivanka and Trajković, Vladimir S.",
year = "2020",
abstract = "Background: The discovery of cisplatin and the subsequent research revealed the importance of dinitrogen-containing moiety for the anticancer action of metal complexes. Moreover, certain diamine ligands alone display cytotoxicity that contributes to the overall activity of corresponding complexes.

Objective: To summarize the current knowledge on the anticancer efficacy, selectivity, and the mechanisms of action of metal complexes with various types of diamine ligands.

Methods: The contribution of aliphatic acyclic, aliphatic cyclic, and aromatic diamine ligands to the anticancer activity and selectivity/toxicity of metal complexes with different metal ions were analyzed by comparison with organic ligand alone and/or conventional platinum-based chemotherapeutics.

Results: The aliphatic acyclic diamine ligands are present mostly in complexes with platinum. Aliphatic cyclic diamines are part of Pt(II), Ru(II) and Au(III) complexes, while aromatic diamine ligands are found in Pt(II), Ru(II), Pd(II) and Ir(III) complexes. The type and oxidation state of metal ions greatly influences the cytotoxicity of metal complexes with aliphatic acyclic diamine ligands. Lipophilicity of organic ligands, dependent on alkyl-side chain length and structure, determines their cellular uptake, with edda and eddp/eddip ligands being most useful in this regard. Aliphatic cyclic diamine ligands improved the activity/toxicity ratio of oxaliplatin-type complexes. The complexes with aromatic diamine ligands remain unexplored regarding their anticancer mechanism. The investigated complexes mainly caused apoptotic or necrotic cell death.

Conclusion: Metal complexes with diamine ligands are promising candidates for efficient and more selective alternatives to conventional platinum-based chemotherapeutics. Further research is required to reveal the chemico-physical properties and molecular mechanisms underlying their biological activity.",
publisher = "Bentham Science",
journal = "Current Medicinal Chemistry",
title = "Current development of metal complexes with diamine ligands as potential anticancer agents",
volume = "27",
number = "3",
pages = "380-410",
doi = "10.2174/0929867325666181031114306"
}

Misirlić-Denčić, S., Poljarević, J., Isaković, A. M., Sabo, T., Marković, I.,& Trajković, V. S.. (2020). Current development of metal complexes with diamine ligands as potential anticancer agents. in Current Medicinal Chemistry
Bentham Science., 27(3), 380-410.
https://doi.org/10.2174/0929867325666181031114306

Misirlić-Denčić S, Poljarević J, Isaković AM, Sabo T, Marković I, Trajković VS. Current development of metal complexes with diamine ligands as potential anticancer agents. in Current Medicinal Chemistry. 2020;27(3):380-410.
doi:10.2174/0929867325666181031114306 .

Misirlić-Denčić, Sonja, Poljarević, Jelena, Isaković, Anđelka M., Sabo, Tibor, Marković, Ivanka, Trajković, Vladimir S., "Current development of metal complexes with diamine ligands as potential anticancer agents" in Current Medicinal Chemistry, 27, no. 3 (2020):380-410,
https://doi.org/10.2174/0929867325666181031114306 . .

TY  - JOUR
AU  - Isaković, Anđelka M.
AU  - Petričević, Saša
AU  - Ristić, Slavica M.
AU  - Popadić, Dušan
AU  - Kravić-Stevović, Tamara
AU  - Zogović, Nevena
AU  - Poljarević, Jelena
AU  - Živanović-Radnić, Tatjana
AU  - Sabo, Tibor
AU  - Isaković, Aleksandra J.
AU  - Marković, Ivanka
AU  - Trajković, Vladimir S.
AU  - Misirlić-Denčić, Sonja
PY  - 2018
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2086
AB  - Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O, O-diethyl-(S, S)-ethylenediamineN, N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspasedependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Melanoma Research
T1  - In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid
VL  - 28
IS  - 1
SP  - 8
EP  - 20
DO  - 10.1097/CMR.0000000000000409
ER  - 

@article{
author = "Isaković, Anđelka M. and Petričević, Saša and Ristić, Slavica M. and Popadić, Dušan and Kravić-Stevović, Tamara and Zogović, Nevena and Poljarević, Jelena and Živanović-Radnić, Tatjana and Sabo, Tibor and Isaković, Aleksandra J. and Marković, Ivanka and Trajković, Vladimir S. and Misirlić-Denčić, Sonja",
year = "2018",
abstract = "Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O, O-diethyl-(S, S)-ethylenediamineN, N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspasedependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Melanoma Research",
title = "In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid",
volume = "28",
number = "1",
pages = "8-20",
doi = "10.1097/CMR.0000000000000409"
}

Isaković, A. M., Petričević, S., Ristić, S. M., Popadić, D., Kravić-Stevović, T., Zogović, N., Poljarević, J., Živanović-Radnić, T., Sabo, T., Isaković, A. J., Marković, I., Trajković, V. S.,& Misirlić-Denčić, S.. (2018). In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid. in Melanoma Research
Lippincott Williams & Wilkins, Philadelphia., 28(1), 8-20.
https://doi.org/10.1097/CMR.0000000000000409

Isaković AM, Petričević S, Ristić SM, Popadić D, Kravić-Stevović T, Zogović N, Poljarević J, Živanović-Radnić T, Sabo T, Isaković AJ, Marković I, Trajković VS, Misirlić-Denčić S. In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid. in Melanoma Research. 2018;28(1):8-20.
doi:10.1097/CMR.0000000000000409 .

Isaković, Anđelka M., Petričević, Saša, Ristić, Slavica M., Popadić, Dušan, Kravić-Stevović, Tamara, Zogović, Nevena, Poljarević, Jelena, Živanović-Radnić, Tatjana, Sabo, Tibor, Isaković, Aleksandra J., Marković, Ivanka, Trajković, Vladimir S., Misirlić-Denčić, Sonja, "In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid" in Melanoma Research, 28, no. 1 (2018):8-20,
https://doi.org/10.1097/CMR.0000000000000409 . .

TY  - JOUR
AU  - Misirlić-Denčić, Sonja
AU  - Poljarević, Jelena
AU  - Isaković, Anđelka M.
AU  - Marković, Ivanka
AU  - Sabo, Tibor
AU  - Grgurić-Šipka, Sanja
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3120
AB  - This study presents the synthesis, characterization, and antitumor action of five new Pt(II) halogenido, chlorido, and iodido complexes with edda type of ligands. (S,S)-Ethylenediamine-N,N-di-2-(3-cyclohexyl)propanoic acid dihydrochloride and its methyl, ethyl, and n-propyl esters were prepared according to the previously reported procedure. All investigated complexes were characterized by IR, ESI-MS (H-1, C-13, and HMBC) NMR spectroscopy, and elemental analysis. Their cytotoxic action was investigated in four human tumor cell lines: promyelocytic (HL-60) and lymphocytic (REH) leukemia, glioma (U251), and lung carcinoma (H460). Cell viability was assessed by acid phosphatase and LDH assay, while oxidative stress and cell death parameters were analyzed by flow cytometry. The results showed that novel Pt(II) complexes exhibited antitumor action superior to precursor ligands, with iodido complexes being more efficient than corresponding chlorido complexes. Human promyelocytic cell line (HL-60) was the most sensitive to antitumor action of all investigated substances and was used for investigation of the underlying mode of antileukemic action. The investigated Pt(II) complexes showed more potent antileukemic action than corresponding Pt(IV) complex, through induction of oxidative stress and apoptosis, evidenced by caspase (8, 9, and 3) activation and phosphatidylserine externalization.
PB  - Wiley, Hoboken
T2  - Chemical Biology and Drug Design
T1  - Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex
VL  - 90
IS  - 2
SP  - 262
EP  - 271
DO  - 10.1111/cbdd.12945
ER  - 

@article{
author = "Misirlić-Denčić, Sonja and Poljarević, Jelena and Isaković, Anđelka M. and Marković, Ivanka and Sabo, Tibor and Grgurić-Šipka, Sanja",
year = "2017",
abstract = "This study presents the synthesis, characterization, and antitumor action of five new Pt(II) halogenido, chlorido, and iodido complexes with edda type of ligands. (S,S)-Ethylenediamine-N,N-di-2-(3-cyclohexyl)propanoic acid dihydrochloride and its methyl, ethyl, and n-propyl esters were prepared according to the previously reported procedure. All investigated complexes were characterized by IR, ESI-MS (H-1, C-13, and HMBC) NMR spectroscopy, and elemental analysis. Their cytotoxic action was investigated in four human tumor cell lines: promyelocytic (HL-60) and lymphocytic (REH) leukemia, glioma (U251), and lung carcinoma (H460). Cell viability was assessed by acid phosphatase and LDH assay, while oxidative stress and cell death parameters were analyzed by flow cytometry. The results showed that novel Pt(II) complexes exhibited antitumor action superior to precursor ligands, with iodido complexes being more efficient than corresponding chlorido complexes. Human promyelocytic cell line (HL-60) was the most sensitive to antitumor action of all investigated substances and was used for investigation of the underlying mode of antileukemic action. The investigated Pt(II) complexes showed more potent antileukemic action than corresponding Pt(IV) complex, through induction of oxidative stress and apoptosis, evidenced by caspase (8, 9, and 3) activation and phosphatidylserine externalization.",
publisher = "Wiley, Hoboken",
journal = "Chemical Biology and Drug Design",
title = "Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex",
volume = "90",
number = "2",
pages = "262-271",
doi = "10.1111/cbdd.12945"
}

Misirlić-Denčić, S., Poljarević, J., Isaković, A. M., Marković, I., Sabo, T.,& Grgurić-Šipka, S.. (2017). Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex. in Chemical Biology and Drug Design
Wiley, Hoboken., 90(2), 262-271.
https://doi.org/10.1111/cbdd.12945

Misirlić-Denčić S, Poljarević J, Isaković AM, Marković I, Sabo T, Grgurić-Šipka S. Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex. in Chemical Biology and Drug Design. 2017;90(2):262-271.
doi:10.1111/cbdd.12945 .

Misirlić-Denčić, Sonja, Poljarević, Jelena, Isaković, Anđelka M., Marković, Ivanka, Sabo, Tibor, Grgurić-Šipka, Sanja, "Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex" in Chemical Biology and Drug Design, 90, no. 2 (2017):262-271,
https://doi.org/10.1111/cbdd.12945 . .

TY  - DATA
AU  - Misirlić-Denčić, Sonja
AU  - Poljarević, Jelena
AU  - Isaković, Anđelka M.
AU  - Marković, Ivanka
AU  - Sabo, Tibor
AU  - Grgurić-Šipka, Sanja
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3121
PB  - Wiley, Hoboken
T2  - Chemical Biology and Drug Design
T1  - Supplementary data for article:           Misirlić Denčić, S.; Poljarević, J.; Isakovic, A. M.; Marković, I.; Sabo, T. J.; Grgurić-Šipka, S. Antileukemic Action of Novel Diamine Pt(II) Halogenido Complexes: Comparison of the Representative Novel Pt(II) with Corresponding Pt(IV) Complex. Chemical Biology and Drug Design 2017, 90 (2), 262–271. https://doi.org/10.1111/cbdd.12945
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3121
ER  - 

@misc{
author = "Misirlić-Denčić, Sonja and Poljarević, Jelena and Isaković, Anđelka M. and Marković, Ivanka and Sabo, Tibor and Grgurić-Šipka, Sanja",
year = "2017",
publisher = "Wiley, Hoboken",
journal = "Chemical Biology and Drug Design",
title = "Supplementary data for article:           Misirlić Denčić, S.; Poljarević, J.; Isakovic, A. M.; Marković, I.; Sabo, T. J.; Grgurić-Šipka, S. Antileukemic Action of Novel Diamine Pt(II) Halogenido Complexes: Comparison of the Representative Novel Pt(II) with Corresponding Pt(IV) Complex. Chemical Biology and Drug Design 2017, 90 (2), 262–271. https://doi.org/10.1111/cbdd.12945",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3121"
}

Misirlić-Denčić, S., Poljarević, J., Isaković, A. M., Marković, I., Sabo, T.,& Grgurić-Šipka, S.. (2017). Supplementary data for article:           Misirlić Denčić, S.; Poljarević, J.; Isakovic, A. M.; Marković, I.; Sabo, T. J.; Grgurić-Šipka, S. Antileukemic Action of Novel Diamine Pt(II) Halogenido Complexes: Comparison of the Representative Novel Pt(II) with Corresponding Pt(IV) Complex. Chemical Biology and Drug Design 2017, 90 (2), 262–271. https://doi.org/10.1111/cbdd.12945. in Chemical Biology and Drug Design
Wiley, Hoboken..
https://hdl.handle.net/21.15107/rcub_cherry_3121

Misirlić-Denčić S, Poljarević J, Isaković AM, Marković I, Sabo T, Grgurić-Šipka S. Supplementary data for article:           Misirlić Denčić, S.; Poljarević, J.; Isakovic, A. M.; Marković, I.; Sabo, T. J.; Grgurić-Šipka, S. Antileukemic Action of Novel Diamine Pt(II) Halogenido Complexes: Comparison of the Representative Novel Pt(II) with Corresponding Pt(IV) Complex. Chemical Biology and Drug Design 2017, 90 (2), 262–271. https://doi.org/10.1111/cbdd.12945. in Chemical Biology and Drug Design. 2017;.
https://hdl.handle.net/21.15107/rcub_cherry_3121 .

Misirlić-Denčić, Sonja, Poljarević, Jelena, Isaković, Anđelka M., Marković, Ivanka, Sabo, Tibor, Grgurić-Šipka, Sanja, "Supplementary data for article:           Misirlić Denčić, S.; Poljarević, J.; Isakovic, A. M.; Marković, I.; Sabo, T. J.; Grgurić-Šipka, S. Antileukemic Action of Novel Diamine Pt(II) Halogenido Complexes: Comparison of the Representative Novel Pt(II) with Corresponding Pt(IV) Complex. Chemical Biology and Drug Design 2017, 90 (2), 262–271. https://doi.org/10.1111/cbdd.12945" in Chemical Biology and Drug Design (2017),
https://hdl.handle.net/21.15107/rcub_cherry_3121 .

TY  - JOUR
AU  - Misirlić-Denčić, Sonja
AU  - Poljarević, Jelena
AU  - Isaković, Anđelka M.
AU  - Marković, Ivanka
AU  - Sabo, Tibor
AU  - Grgurić-Šipka, Sanja
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2483
AB  - This study presents the synthesis, characterization, and antitumor action of five new Pt(II) halogenido, chlorido, and iodido complexes with edda type of ligands. (S,S)-Ethylenediamine-N,N-di-2-(3-cyclohexyl)propanoic acid dihydrochloride and its methyl, ethyl, and n-propyl esters were prepared according to the previously reported procedure. All investigated complexes were characterized by IR, ESI-MS (H-1, C-13, and HMBC) NMR spectroscopy, and elemental analysis. Their cytotoxic action was investigated in four human tumor cell lines: promyelocytic (HL-60) and lymphocytic (REH) leukemia, glioma (U251), and lung carcinoma (H460). Cell viability was assessed by acid phosphatase and LDH assay, while oxidative stress and cell death parameters were analyzed by flow cytometry. The results showed that novel Pt(II) complexes exhibited antitumor action superior to precursor ligands, with iodido complexes being more efficient than corresponding chlorido complexes. Human promyelocytic cell line (HL-60) was the most sensitive to antitumor action of all investigated substances and was used for investigation of the underlying mode of antileukemic action. The investigated Pt(II) complexes showed more potent antileukemic action than corresponding Pt(IV) complex, through induction of oxidative stress and apoptosis, evidenced by caspase (8, 9, and 3) activation and phosphatidylserine externalization.
PB  - Wiley, Hoboken
T2  - Chemical Biology and Drug Design
T1  - Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex
VL  - 90
IS  - 2
SP  - 262
EP  - 271
DO  - 10.1111/cbdd.12945
ER  - 

@article{
author = "Misirlić-Denčić, Sonja and Poljarević, Jelena and Isaković, Anđelka M. and Marković, Ivanka and Sabo, Tibor and Grgurić-Šipka, Sanja",
year = "2017",
abstract = "This study presents the synthesis, characterization, and antitumor action of five new Pt(II) halogenido, chlorido, and iodido complexes with edda type of ligands. (S,S)-Ethylenediamine-N,N-di-2-(3-cyclohexyl)propanoic acid dihydrochloride and its methyl, ethyl, and n-propyl esters were prepared according to the previously reported procedure. All investigated complexes were characterized by IR, ESI-MS (H-1, C-13, and HMBC) NMR spectroscopy, and elemental analysis. Their cytotoxic action was investigated in four human tumor cell lines: promyelocytic (HL-60) and lymphocytic (REH) leukemia, glioma (U251), and lung carcinoma (H460). Cell viability was assessed by acid phosphatase and LDH assay, while oxidative stress and cell death parameters were analyzed by flow cytometry. The results showed that novel Pt(II) complexes exhibited antitumor action superior to precursor ligands, with iodido complexes being more efficient than corresponding chlorido complexes. Human promyelocytic cell line (HL-60) was the most sensitive to antitumor action of all investigated substances and was used for investigation of the underlying mode of antileukemic action. The investigated Pt(II) complexes showed more potent antileukemic action than corresponding Pt(IV) complex, through induction of oxidative stress and apoptosis, evidenced by caspase (8, 9, and 3) activation and phosphatidylserine externalization.",
publisher = "Wiley, Hoboken",
journal = "Chemical Biology and Drug Design",
title = "Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex",
volume = "90",
number = "2",
pages = "262-271",
doi = "10.1111/cbdd.12945"
}

Misirlić-Denčić, S., Poljarević, J., Isaković, A. M., Marković, I., Sabo, T.,& Grgurić-Šipka, S.. (2017). Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex. in Chemical Biology and Drug Design
Wiley, Hoboken., 90(2), 262-271.
https://doi.org/10.1111/cbdd.12945

Misirlić-Denčić S, Poljarević J, Isaković AM, Marković I, Sabo T, Grgurić-Šipka S. Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex. in Chemical Biology and Drug Design. 2017;90(2):262-271.
doi:10.1111/cbdd.12945 .

Misirlić-Denčić, Sonja, Poljarević, Jelena, Isaković, Anđelka M., Marković, Ivanka, Sabo, Tibor, Grgurić-Šipka, Sanja, "Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex" in Chemical Biology and Drug Design, 90, no. 2 (2017):262-271,
https://doi.org/10.1111/cbdd.12945 . .

TY  - JOUR
AU  - Todorović, Tamara
AU  - Grubišić, Sonja
AU  - Pregelj, Matej
AU  - Jagodić, Marko
AU  - Misirlić-Denčić, Sonja
AU  - Dulović, Marija
AU  - Marković, Ivanka
AU  - Klisurić, Olivera
AU  - Malešević, Aleksandar
AU  - Mitić, Dragana
AU  - Anđelković, Katarina K.
AU  - Filipović, Nenad R.
PY  - 2015
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1753
AB  - Copper(II) complexes with the condensation derivative of methyl hydrazinoacetate and 2-acetylpyridine were synthesized. The X-ray crystal structures for both complexes revealed that they are polymerized isomers. A common feature of both complexes is the bidentate coordination of the ligand by one hydrazone and one pyridine nitrogen atom. In the monomeric complex, the copper(II) center is tetracoordinate, whereas dimerization through chlorido bridges results in a pentacoordinate arrangement about the metal ions in the dimer. The electronic and magnetic properties of both complexes are discussed on the basis of their X-ray structures, electron paramagnetic resonance (EPR) spectroscopy studies, and superconducting quantum interference device (SQUID) magnetization measurements combined with DFT calculations. Magnetostructural comparisons with structurally similar copper(II) complexes are also provided, and a possible correlation has been established. The antitumor activities of the Cu-II complexes were investigated against six different cancer cell lines, and the results suggest that the antiglioma action of the dimeric species is based on oxidative-stress-mediated phosphatidylserine externalization and caspase activation, which indicate apoptosis.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - European Journal of Inorganic Chemistry
T1  - Structural, Magnetic, DFT, and Biological Studies of Mononuclear and Dinuclear Cu-II Complexes with Bidentate N-Heteroaromatic Schiff Base Ligands
IS  - 23
SP  - 3921
EP  - 3931
DO  - 10.1002/ejic.201500349
ER  - 

@article{
author = "Todorović, Tamara and Grubišić, Sonja and Pregelj, Matej and Jagodić, Marko and Misirlić-Denčić, Sonja and Dulović, Marija and Marković, Ivanka and Klisurić, Olivera and Malešević, Aleksandar and Mitić, Dragana and Anđelković, Katarina K. and Filipović, Nenad R.",
year = "2015",
abstract = "Copper(II) complexes with the condensation derivative of methyl hydrazinoacetate and 2-acetylpyridine were synthesized. The X-ray crystal structures for both complexes revealed that they are polymerized isomers. A common feature of both complexes is the bidentate coordination of the ligand by one hydrazone and one pyridine nitrogen atom. In the monomeric complex, the copper(II) center is tetracoordinate, whereas dimerization through chlorido bridges results in a pentacoordinate arrangement about the metal ions in the dimer. The electronic and magnetic properties of both complexes are discussed on the basis of their X-ray structures, electron paramagnetic resonance (EPR) spectroscopy studies, and superconducting quantum interference device (SQUID) magnetization measurements combined with DFT calculations. Magnetostructural comparisons with structurally similar copper(II) complexes are also provided, and a possible correlation has been established. The antitumor activities of the Cu-II complexes were investigated against six different cancer cell lines, and the results suggest that the antiglioma action of the dimeric species is based on oxidative-stress-mediated phosphatidylserine externalization and caspase activation, which indicate apoptosis.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "European Journal of Inorganic Chemistry",
title = "Structural, Magnetic, DFT, and Biological Studies of Mononuclear and Dinuclear Cu-II Complexes with Bidentate N-Heteroaromatic Schiff Base Ligands",
number = "23",
pages = "3921-3931",
doi = "10.1002/ejic.201500349"
}

Todorović, T., Grubišić, S., Pregelj, M., Jagodić, M., Misirlić-Denčić, S., Dulović, M., Marković, I., Klisurić, O., Malešević, A., Mitić, D., Anđelković, K. K.,& Filipović, N. R.. (2015). Structural, Magnetic, DFT, and Biological Studies of Mononuclear and Dinuclear Cu-II Complexes with Bidentate N-Heteroaromatic Schiff Base Ligands. in European Journal of Inorganic Chemistry
Wiley-V C H Verlag Gmbh, Weinheim.(23), 3921-3931.
https://doi.org/10.1002/ejic.201500349

Todorović T, Grubišić S, Pregelj M, Jagodić M, Misirlić-Denčić S, Dulović M, Marković I, Klisurić O, Malešević A, Mitić D, Anđelković KK, Filipović NR. Structural, Magnetic, DFT, and Biological Studies of Mononuclear and Dinuclear Cu-II Complexes with Bidentate N-Heteroaromatic Schiff Base Ligands. in European Journal of Inorganic Chemistry. 2015;(23):3921-3931.
doi:10.1002/ejic.201500349 .

Todorović, Tamara, Grubišić, Sonja, Pregelj, Matej, Jagodić, Marko, Misirlić-Denčić, Sonja, Dulović, Marija, Marković, Ivanka, Klisurić, Olivera, Malešević, Aleksandar, Mitić, Dragana, Anđelković, Katarina K., Filipović, Nenad R., "Structural, Magnetic, DFT, and Biological Studies of Mononuclear and Dinuclear Cu-II Complexes with Bidentate N-Heteroaromatic Schiff Base Ligands" in European Journal of Inorganic Chemistry, no. 23 (2015):3921-3931,
https://doi.org/10.1002/ejic.201500349 . .

TY  - DATA
AU  - Todorović, Tamara
AU  - Grubišić, Sonja
AU  - Pregelj, Matej
AU  - Jagodić, Marko
AU  - Misirlić-Denčić, Sonja
AU  - Dulović, Marija
AU  - Marković, Ivanka
AU  - Klisurić, Olivera
AU  - Malešević, Aleksandar
AU  - Mitić, Dragana
AU  - Anđelković, Katarina K.
AU  - Filipović, Nenad R.
PY  - 2015
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3431
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - European Journal of Inorganic Chemistry
T1  - Supplementary data for article: Todorovic, T.; Grubišic, S.; Pregelj, M.; Jagodič, M.; Misirlic-Denčic, S.; Dulovic, M.; Markovic, I.; Klisuric, O.; Maleševic, A.; Mitic, D.; et al. Structural, Magnetic, DFT, and Biological Studies of Mononuclear and Dinuclear CuII Complexes with Bidentate N-Heteroaromatic Schiff Base Ligands. European Journal of Inorganic Chemistry 2015, 2015 (23), 3921–3931. https://doi.org/10.1002/ejic.201500349
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3431
ER  - 

@misc{
author = "Todorović, Tamara and Grubišić, Sonja and Pregelj, Matej and Jagodić, Marko and Misirlić-Denčić, Sonja and Dulović, Marija and Marković, Ivanka and Klisurić, Olivera and Malešević, Aleksandar and Mitić, Dragana and Anđelković, Katarina K. and Filipović, Nenad R.",
year = "2015",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "European Journal of Inorganic Chemistry",
title = "Supplementary data for article: Todorovic, T.; Grubišic, S.; Pregelj, M.; Jagodič, M.; Misirlic-Denčic, S.; Dulovic, M.; Markovic, I.; Klisuric, O.; Maleševic, A.; Mitic, D.; et al. Structural, Magnetic, DFT, and Biological Studies of Mononuclear and Dinuclear CuII Complexes with Bidentate N-Heteroaromatic Schiff Base Ligands. European Journal of Inorganic Chemistry 2015, 2015 (23), 3921–3931. https://doi.org/10.1002/ejic.201500349",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3431"
}

Todorović, T., Grubišić, S., Pregelj, M., Jagodić, M., Misirlić-Denčić, S., Dulović, M., Marković, I., Klisurić, O., Malešević, A., Mitić, D., Anđelković, K. K.,& Filipović, N. R.. (2015). Supplementary data for article: Todorovic, T.; Grubišic, S.; Pregelj, M.; Jagodič, M.; Misirlic-Denčic, S.; Dulovic, M.; Markovic, I.; Klisuric, O.; Maleševic, A.; Mitic, D.; et al. Structural, Magnetic, DFT, and Biological Studies of Mononuclear and Dinuclear CuII Complexes with Bidentate N-Heteroaromatic Schiff Base Ligands. European Journal of Inorganic Chemistry 2015, 2015 (23), 3921–3931. https://doi.org/10.1002/ejic.201500349. in European Journal of Inorganic Chemistry
Wiley-V C H Verlag Gmbh, Weinheim..
https://hdl.handle.net/21.15107/rcub_cherry_3431

Todorović T, Grubišić S, Pregelj M, Jagodić M, Misirlić-Denčić S, Dulović M, Marković I, Klisurić O, Malešević A, Mitić D, Anđelković KK, Filipović NR. Supplementary data for article: Todorovic, T.; Grubišic, S.; Pregelj, M.; Jagodič, M.; Misirlic-Denčic, S.; Dulovic, M.; Markovic, I.; Klisuric, O.; Maleševic, A.; Mitic, D.; et al. Structural, Magnetic, DFT, and Biological Studies of Mononuclear and Dinuclear CuII Complexes with Bidentate N-Heteroaromatic Schiff Base Ligands. European Journal of Inorganic Chemistry 2015, 2015 (23), 3921–3931. https://doi.org/10.1002/ejic.201500349. in European Journal of Inorganic Chemistry. 2015;.
https://hdl.handle.net/21.15107/rcub_cherry_3431 .

Todorović, Tamara, Grubišić, Sonja, Pregelj, Matej, Jagodić, Marko, Misirlić-Denčić, Sonja, Dulović, Marija, Marković, Ivanka, Klisurić, Olivera, Malešević, Aleksandar, Mitić, Dragana, Anđelković, Katarina K., Filipović, Nenad R., "Supplementary data for article: Todorovic, T.; Grubišic, S.; Pregelj, M.; Jagodič, M.; Misirlic-Denčic, S.; Dulovic, M.; Markovic, I.; Klisuric, O.; Maleševic, A.; Mitic, D.; et al. Structural, Magnetic, DFT, and Biological Studies of Mononuclear and Dinuclear CuII Complexes with Bidentate N-Heteroaromatic Schiff Base Ligands. European Journal of Inorganic Chemistry 2015, 2015 (23), 3921–3931. https://doi.org/10.1002/ejic.201500349" in European Journal of Inorganic Chemistry (2015),
https://hdl.handle.net/21.15107/rcub_cherry_3431 .

TY  - JOUR
AU  - Filipović, Nenad R.
AU  - Polović, Natalija
AU  - Rašković, Brankica
AU  - Misirlić-Denčić, Sonja
AU  - Dulović, Marija
AU  - Savić, Milena
AU  - Nikšić, Miomir
AU  - Mitić, Dragana
AU  - Anđelković, Katarina K.
AU  - Todorović, Tamara
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1787
AB  - New square-planar Pd(II) and Pt(II) complexes with 8-quinolinecarboxaldehyde selenosemicarbazone have been synthesized and characterized by use of elemental analysis, molar conductivity measurements, and IR and NMR spectroscopy. The cytotoxic activity of the ligand, new Pt(II) and Pd(II) compounds, and previously synthesized Pd(II), Pt(II), Cd(II), and Ni(II) complexes with the analogous ligand, 2-quinolinecarboxaldehyde selenosemicarbazone, was tested against two human cancer cell lines: lung carcinoma (H460) and glioma (U251). The potential of these compounds to induce perturbations of the H460 cell cycle was also evaluated. These substances had an excellent radical-scavenging effect against ABTS radical cations. The best antimicrobial activity, among two yeasts and eight bacterial strains tested, was against Bacillus cereus.
PB  - Springer Wien, Wien
T2  - Monatshefte Fur Chemie
T1  - Biological activity of two isomeric N-heteroaromatic selenosemicarbazones and their metal complexes
VL  - 145
IS  - 7
SP  - 1089
EP  - 1099
DO  - 10.1007/s00706-014-1197-6
ER  - 

@article{
author = "Filipović, Nenad R. and Polović, Natalija and Rašković, Brankica and Misirlić-Denčić, Sonja and Dulović, Marija and Savić, Milena and Nikšić, Miomir and Mitić, Dragana and Anđelković, Katarina K. and Todorović, Tamara",
year = "2014",
abstract = "New square-planar Pd(II) and Pt(II) complexes with 8-quinolinecarboxaldehyde selenosemicarbazone have been synthesized and characterized by use of elemental analysis, molar conductivity measurements, and IR and NMR spectroscopy. The cytotoxic activity of the ligand, new Pt(II) and Pd(II) compounds, and previously synthesized Pd(II), Pt(II), Cd(II), and Ni(II) complexes with the analogous ligand, 2-quinolinecarboxaldehyde selenosemicarbazone, was tested against two human cancer cell lines: lung carcinoma (H460) and glioma (U251). The potential of these compounds to induce perturbations of the H460 cell cycle was also evaluated. These substances had an excellent radical-scavenging effect against ABTS radical cations. The best antimicrobial activity, among two yeasts and eight bacterial strains tested, was against Bacillus cereus.",
publisher = "Springer Wien, Wien",
journal = "Monatshefte Fur Chemie",
title = "Biological activity of two isomeric N-heteroaromatic selenosemicarbazones and their metal complexes",
volume = "145",
number = "7",
pages = "1089-1099",
doi = "10.1007/s00706-014-1197-6"
}

Filipović, N. R., Polović, N., Rašković, B., Misirlić-Denčić, S., Dulović, M., Savić, M., Nikšić, M., Mitić, D., Anđelković, K. K.,& Todorović, T.. (2014). Biological activity of two isomeric N-heteroaromatic selenosemicarbazones and their metal complexes. in Monatshefte Fur Chemie
Springer Wien, Wien., 145(7), 1089-1099.
https://doi.org/10.1007/s00706-014-1197-6

Filipović NR, Polović N, Rašković B, Misirlić-Denčić S, Dulović M, Savić M, Nikšić M, Mitić D, Anđelković KK, Todorović T. Biological activity of two isomeric N-heteroaromatic selenosemicarbazones and their metal complexes. in Monatshefte Fur Chemie. 2014;145(7):1089-1099.
doi:10.1007/s00706-014-1197-6 .

Filipović, Nenad R., Polović, Natalija, Rašković, Brankica, Misirlić-Denčić, Sonja, Dulović, Marija, Savić, Milena, Nikšić, Miomir, Mitić, Dragana, Anđelković, Katarina K., Todorović, Tamara, "Biological activity of two isomeric N-heteroaromatic selenosemicarbazones and their metal complexes" in Monatshefte Fur Chemie, 145, no. 7 (2014):1089-1099,
https://doi.org/10.1007/s00706-014-1197-6 . .

TY  - DATA
AU  - Filipović, Nenad R.
AU  - Polović, Natalija
AU  - Rašković, Brankica
AU  - Misirlić-Denčić, Sonja
AU  - Dulović, Marija
AU  - Savić, Milena
AU  - Nikšić, Miomir
AU  - Mitić, Dragana
AU  - Anđelković, Katarina K.
AU  - Todorović, Tamara
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3683
PB  - Springer Wien, Wien
T2  - Monatshefte Fur Chemie
T1  - Supplementary data for the article: Filipović, N.; Polović, N.; Rašković, B.; Misirlić-Denčić, S.; Dulović, M.; Savić, M.; Nikšić, M.; Mitić, D.; Ancrossed D Signelković, K.; Todorović, T. Biological Activity of Two Isomeric N-Heteroaromatic Selenosemicarbazones and Their Metal Complexes. Monatshefte fur Chemie 2014, 145 (7), 1089–1099. https://doi.org/10.1007/s00706-014-1197-6
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3683
ER  - 

@misc{
author = "Filipović, Nenad R. and Polović, Natalija and Rašković, Brankica and Misirlić-Denčić, Sonja and Dulović, Marija and Savić, Milena and Nikšić, Miomir and Mitić, Dragana and Anđelković, Katarina K. and Todorović, Tamara",
year = "2014",
publisher = "Springer Wien, Wien",
journal = "Monatshefte Fur Chemie",
title = "Supplementary data for the article: Filipović, N.; Polović, N.; Rašković, B.; Misirlić-Denčić, S.; Dulović, M.; Savić, M.; Nikšić, M.; Mitić, D.; Ancrossed D Signelković, K.; Todorović, T. Biological Activity of Two Isomeric N-Heteroaromatic Selenosemicarbazones and Their Metal Complexes. Monatshefte fur Chemie 2014, 145 (7), 1089–1099. https://doi.org/10.1007/s00706-014-1197-6",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3683"
}

Filipović, N. R., Polović, N., Rašković, B., Misirlić-Denčić, S., Dulović, M., Savić, M., Nikšić, M., Mitić, D., Anđelković, K. K.,& Todorović, T.. (2014). Supplementary data for the article: Filipović, N.; Polović, N.; Rašković, B.; Misirlić-Denčić, S.; Dulović, M.; Savić, M.; Nikšić, M.; Mitić, D.; Ancrossed D Signelković, K.; Todorović, T. Biological Activity of Two Isomeric N-Heteroaromatic Selenosemicarbazones and Their Metal Complexes. Monatshefte fur Chemie 2014, 145 (7), 1089–1099. https://doi.org/10.1007/s00706-014-1197-6. in Monatshefte Fur Chemie
Springer Wien, Wien..
https://hdl.handle.net/21.15107/rcub_cherry_3683

Filipović NR, Polović N, Rašković B, Misirlić-Denčić S, Dulović M, Savić M, Nikšić M, Mitić D, Anđelković KK, Todorović T. Supplementary data for the article: Filipović, N.; Polović, N.; Rašković, B.; Misirlić-Denčić, S.; Dulović, M.; Savić, M.; Nikšić, M.; Mitić, D.; Ancrossed D Signelković, K.; Todorović, T. Biological Activity of Two Isomeric N-Heteroaromatic Selenosemicarbazones and Their Metal Complexes. Monatshefte fur Chemie 2014, 145 (7), 1089–1099. https://doi.org/10.1007/s00706-014-1197-6. in Monatshefte Fur Chemie. 2014;.
https://hdl.handle.net/21.15107/rcub_cherry_3683 .

Filipović, Nenad R., Polović, Natalija, Rašković, Brankica, Misirlić-Denčić, Sonja, Dulović, Marija, Savić, Milena, Nikšić, Miomir, Mitić, Dragana, Anđelković, Katarina K., Todorović, Tamara, "Supplementary data for the article: Filipović, N.; Polović, N.; Rašković, B.; Misirlić-Denčić, S.; Dulović, M.; Savić, M.; Nikšić, M.; Mitić, D.; Ancrossed D Signelković, K.; Todorović, T. Biological Activity of Two Isomeric N-Heteroaromatic Selenosemicarbazones and Their Metal Complexes. Monatshefte fur Chemie 2014, 145 (7), 1089–1099. https://doi.org/10.1007/s00706-014-1197-6" in Monatshefte Fur Chemie (2014),
https://hdl.handle.net/21.15107/rcub_cherry_3683 .

TY  - JOUR
AU  - Savić, Aleksandar
AU  - Misirlić-Denčić, Sonja
AU  - Dulović, Marija
AU  - Mihajlović-Lalić, Ljiljana
AU  - Jovanović, Maja
AU  - Grgurić-Šipka, Sanja
AU  - Marković, Ivanka
AU  - Sabo, Tibor
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1811
AB  - This study involves the synthesis and characterization of novel cyclohexyl 1,3-propanediamine-N, N'-diacetate molecules as well as investigation of their cytotoxic action. New acid 1a was synthesized by reaction between (S)-2-amino-3-cyclohexylpropanoic acid and 1,3-dibromopropane, while the esters (1b-1e) derived from this acid were obtained by reaction of the corresponding absolute alcohol, thionyl chloride and synthesized acid. All compounds were characterized by IR, ESI-MS, (H-1, C-13 and HSQC) NMR spectroscopy and elemental analysis. The cytotoxic activity of all compounds was tested on several tumour cell lines: human (U251) and rat (C6) glioma, human promyelocytic leukaemia (HL-60), human neuroblastoma (SHSY-5Y) and mouse fibrosarcoma (L929) as well as primary rat astrocytes. The present study reveals potent antitumour activity of novel purely organic compounds (1a-1e), which was most pronounced in human glioma (U251) cells. The esterification is required for the novel compounds' cytotoxic action since the n-butyl ester 1e was the most efficient compound. Importantly, n-butyl ester 1e was more toxic to glioma cells in comparison to rat astrocytes, with 24-h IC50 values lower than those for cisplatin. n-Butyl ester 1e induced production of reactive oxygen species (ROS) and caused an oxidative- stress-derived accumulation of glioma cells in the G(0)/G(1) phase of the cell cycle, as well as caspase activation and DNA fragmentation, suggesting that apoptosis induction plays an important role in the novel compounds' antiglioma action. (C) 2014 Elsevier Inc. All rights reserved.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Bioorganic Chemistry
T1  - Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters
VL  - 54
SP  - 73
EP  - 80
DO  - 10.1016/j.bioorg.2014.04.006
ER  - 

@article{
author = "Savić, Aleksandar and Misirlić-Denčić, Sonja and Dulović, Marija and Mihajlović-Lalić, Ljiljana and Jovanović, Maja and Grgurić-Šipka, Sanja and Marković, Ivanka and Sabo, Tibor",
year = "2014",
abstract = "This study involves the synthesis and characterization of novel cyclohexyl 1,3-propanediamine-N, N'-diacetate molecules as well as investigation of their cytotoxic action. New acid 1a was synthesized by reaction between (S)-2-amino-3-cyclohexylpropanoic acid and 1,3-dibromopropane, while the esters (1b-1e) derived from this acid were obtained by reaction of the corresponding absolute alcohol, thionyl chloride and synthesized acid. All compounds were characterized by IR, ESI-MS, (H-1, C-13 and HSQC) NMR spectroscopy and elemental analysis. The cytotoxic activity of all compounds was tested on several tumour cell lines: human (U251) and rat (C6) glioma, human promyelocytic leukaemia (HL-60), human neuroblastoma (SHSY-5Y) and mouse fibrosarcoma (L929) as well as primary rat astrocytes. The present study reveals potent antitumour activity of novel purely organic compounds (1a-1e), which was most pronounced in human glioma (U251) cells. The esterification is required for the novel compounds' cytotoxic action since the n-butyl ester 1e was the most efficient compound. Importantly, n-butyl ester 1e was more toxic to glioma cells in comparison to rat astrocytes, with 24-h IC50 values lower than those for cisplatin. n-Butyl ester 1e induced production of reactive oxygen species (ROS) and caused an oxidative- stress-derived accumulation of glioma cells in the G(0)/G(1) phase of the cell cycle, as well as caspase activation and DNA fragmentation, suggesting that apoptosis induction plays an important role in the novel compounds' antiglioma action. (C) 2014 Elsevier Inc. All rights reserved.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Bioorganic Chemistry",
title = "Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters",
volume = "54",
pages = "73-80",
doi = "10.1016/j.bioorg.2014.04.006"
}

Savić, A., Misirlić-Denčić, S., Dulović, M., Mihajlović-Lalić, L., Jovanović, M., Grgurić-Šipka, S., Marković, I.,& Sabo, T.. (2014). Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters. in Bioorganic Chemistry
Academic Press Inc Elsevier Science, San Diego., 54, 73-80.
https://doi.org/10.1016/j.bioorg.2014.04.006

Savić A, Misirlić-Denčić S, Dulović M, Mihajlović-Lalić L, Jovanović M, Grgurić-Šipka S, Marković I, Sabo T. Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters. in Bioorganic Chemistry. 2014;54:73-80.
doi:10.1016/j.bioorg.2014.04.006 .

Savić, Aleksandar, Misirlić-Denčić, Sonja, Dulović, Marija, Mihajlović-Lalić, Ljiljana, Jovanović, Maja, Grgurić-Šipka, Sanja, Marković, Ivanka, Sabo, Tibor, "Synthesis, characterization and ROS-mediated cytotoxic action of novel (S, S)-1,3-propanediamine-N,N '-di-2-(3-cyclohexyl)propanoic acid and corresponding esters" in Bioorganic Chemistry, 54 (2014):73-80,
https://doi.org/10.1016/j.bioorg.2014.04.006 . .

TY  - JOUR
AU  - Misirlić-Denčić, Sonja
AU  - Poljarević, Jelena
AU  - Vilimanovich, Urosh
AU  - Bogdanović, Andrija
AU  - Isaković, Aleksandra J.
AU  - Kravić-Stevović, Tamara
AU  - Dulović, Marija
AU  - Zogović, Nevena
AU  - Isaković, Anđelka M.
AU  - Grgurić-Šipka, Sanja
AU  - Bumbasirevic, Vladimir
AU  - Sabo, Tibor
AU  - Trajković, Vladimir S.
AU  - Marković, Ivanka
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1279
AB  - We investigated the cytotoxicity of recently synthesized (S,S)-ethyleridiamine-N,N'-di-2-(3-cyclohexyl)propanoic acid esters toward human leukemic cell lines and healthy blood mononuclear cells. Cell viability was assessed by acid phosphatase assay, apoptosis, and differentiation were analyzed by flow cytometry and electron microscopy, while intracellular localization of apoptosis-inducing factor (AIF) was determined by immunoblotting. It was demonstrated that methyl, ethyl, and n-propyl esters were toxic to HL-60, REH, MOLT-4, KG-1, JVM-2, and K-562 leukemic cell lines, while the nonesterified parental compound and n-butyl ester were devoid of cytotoxic action. The ethyl ester exhibited the highest cytotoxic activity (IC50 10.7 mu M-45.4 mu M), which was comparable to that of the prototypical anticancer drug cisplatin. The observed cytotoxic effect in HL-60 cells was associated with an increase in superoxide production and mitochondrial membrane depolarization, leading to apoptotic cell death characterized by phosphatidylserine externalization and DNA fragmentation in the absence of autophagic response. DNA fragmentation preceded caspase activation and followed AIF translocation from mitochondria to nucleus, which was indicative of caspase-independent apoptotic cell death. HL-60 cells treated with subtoxic concentration of the compound displayed morphological signs of granulocytic differentiation (nuclear indentations and presence of cytoplasmic primary granules), as well as an increased expression of differentiation markers CD11b and CD15. The cyclohexyl analogues of ethylenediamine dipropanoic acid were also toxic to peripheral blood mononuclear cells of both healthy controls and leukemic patients, the latter being more sensitive. Our data demonstrate that the toxicity of the investigated cyclohexyl compounds against leukemic cell lines is mediated by caspase-independent apoptosis associated with oxidative stress, mitochondrial dysfunction, and AIF translocation.
PB  - Amer Chemical Soc, Washington
T2  - Chemical Research in Toxicology
T1  - Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells
VL  - 25
IS  - 4
SP  - 931
EP  - 939
DO  - 10.1021/tx3000329
ER  - 

@article{
author = "Misirlić-Denčić, Sonja and Poljarević, Jelena and Vilimanovich, Urosh and Bogdanović, Andrija and Isaković, Aleksandra J. and Kravić-Stevović, Tamara and Dulović, Marija and Zogović, Nevena and Isaković, Anđelka M. and Grgurić-Šipka, Sanja and Bumbasirevic, Vladimir and Sabo, Tibor and Trajković, Vladimir S. and Marković, Ivanka",
year = "2012",
abstract = "We investigated the cytotoxicity of recently synthesized (S,S)-ethyleridiamine-N,N'-di-2-(3-cyclohexyl)propanoic acid esters toward human leukemic cell lines and healthy blood mononuclear cells. Cell viability was assessed by acid phosphatase assay, apoptosis, and differentiation were analyzed by flow cytometry and electron microscopy, while intracellular localization of apoptosis-inducing factor (AIF) was determined by immunoblotting. It was demonstrated that methyl, ethyl, and n-propyl esters were toxic to HL-60, REH, MOLT-4, KG-1, JVM-2, and K-562 leukemic cell lines, while the nonesterified parental compound and n-butyl ester were devoid of cytotoxic action. The ethyl ester exhibited the highest cytotoxic activity (IC50 10.7 mu M-45.4 mu M), which was comparable to that of the prototypical anticancer drug cisplatin. The observed cytotoxic effect in HL-60 cells was associated with an increase in superoxide production and mitochondrial membrane depolarization, leading to apoptotic cell death characterized by phosphatidylserine externalization and DNA fragmentation in the absence of autophagic response. DNA fragmentation preceded caspase activation and followed AIF translocation from mitochondria to nucleus, which was indicative of caspase-independent apoptotic cell death. HL-60 cells treated with subtoxic concentration of the compound displayed morphological signs of granulocytic differentiation (nuclear indentations and presence of cytoplasmic primary granules), as well as an increased expression of differentiation markers CD11b and CD15. The cyclohexyl analogues of ethylenediamine dipropanoic acid were also toxic to peripheral blood mononuclear cells of both healthy controls and leukemic patients, the latter being more sensitive. Our data demonstrate that the toxicity of the investigated cyclohexyl compounds against leukemic cell lines is mediated by caspase-independent apoptosis associated with oxidative stress, mitochondrial dysfunction, and AIF translocation.",
publisher = "Amer Chemical Soc, Washington",
journal = "Chemical Research in Toxicology",
title = "Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells",
volume = "25",
number = "4",
pages = "931-939",
doi = "10.1021/tx3000329"
}

Misirlić-Denčić, S., Poljarević, J., Vilimanovich, U., Bogdanović, A., Isaković, A. J., Kravić-Stevović, T., Dulović, M., Zogović, N., Isaković, A. M., Grgurić-Šipka, S., Bumbasirevic, V., Sabo, T., Trajković, V. S.,& Marković, I.. (2012). Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells. in Chemical Research in Toxicology
Amer Chemical Soc, Washington., 25(4), 931-939.
https://doi.org/10.1021/tx3000329

Misirlić-Denčić S, Poljarević J, Vilimanovich U, Bogdanović A, Isaković AJ, Kravić-Stevović T, Dulović M, Zogović N, Isaković AM, Grgurić-Šipka S, Bumbasirevic V, Sabo T, Trajković VS, Marković I. Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells. in Chemical Research in Toxicology. 2012;25(4):931-939.
doi:10.1021/tx3000329 .

Misirlić-Denčić, Sonja, Poljarević, Jelena, Vilimanovich, Urosh, Bogdanović, Andrija, Isaković, Aleksandra J., Kravić-Stevović, Tamara, Dulović, Marija, Zogović, Nevena, Isaković, Anđelka M., Grgurić-Šipka, Sanja, Bumbasirevic, Vladimir, Sabo, Tibor, Trajković, Vladimir S., Marković, Ivanka, "Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells" in Chemical Research in Toxicology, 25, no. 4 (2012):931-939,
https://doi.org/10.1021/tx3000329 . .

TY  - JOUR
AU  - Savić, Aleksandar
AU  - Dulović, Marija
AU  - Poljarević, Jelena
AU  - Misirlić-Denčić, Sonja
AU  - Jovanović, Maja
AU  - Bogdanović, Andrija
AU  - Trajković, Vladimir S.
AU  - Sabo, Tibor
AU  - Grgurić-Šipka, Sanja
AU  - Marković, Ivanka
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1215
AB  - Herein we describe the synthesis, characterization, and anticancer activity of novel p-cymeneruthenium(II) complexes containing methyl, ethyl, n-propyl, and n-butyl esters of (S, S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid. The results of IR, UV/Vis, ESIMS, (1)H, and (13)C NMR characterization reveal that ligand coordination occurs through nitrogen donor atoms of the ester ligands, with the organoruthenium moiety being kept in complex. These ruthenium(II) complexes are cytotoxic toward various cancer cell lines including leukemic HL-60, K562, and REH cells (IC(50) : 1.0-20.2 mu m), with the n-butyl ester complex being the most effective. It causes apoptotic cell death associated with mitochondrial depolarization, caspase activation, phosphatidylserine exposure, and DNA fragmentation. Importantly, the n-butyl ester complex is more effective against leukemic patients' blood mononuclear cells relative to those from healthy control subjects, thus indicating a fairly selective antileukemic action of Ru(II)-based compounds.
PB  - Wiley-Blackwell, Malden
T2  - ChemMedChem
T1  - Synthesis and in vitro Anticancer Activity of Ruthenium-Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-diacetate-Type Ligands
VL  - 6
IS  - 10
SP  - 1884
EP  - 1891
DO  - 10.1002/cmdc.201100232
ER  - 

@article{
author = "Savić, Aleksandar and Dulović, Marija and Poljarević, Jelena and Misirlić-Denčić, Sonja and Jovanović, Maja and Bogdanović, Andrija and Trajković, Vladimir S. and Sabo, Tibor and Grgurić-Šipka, Sanja and Marković, Ivanka",
year = "2011",
abstract = "Herein we describe the synthesis, characterization, and anticancer activity of novel p-cymeneruthenium(II) complexes containing methyl, ethyl, n-propyl, and n-butyl esters of (S, S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid. The results of IR, UV/Vis, ESIMS, (1)H, and (13)C NMR characterization reveal that ligand coordination occurs through nitrogen donor atoms of the ester ligands, with the organoruthenium moiety being kept in complex. These ruthenium(II) complexes are cytotoxic toward various cancer cell lines including leukemic HL-60, K562, and REH cells (IC(50) : 1.0-20.2 mu m), with the n-butyl ester complex being the most effective. It causes apoptotic cell death associated with mitochondrial depolarization, caspase activation, phosphatidylserine exposure, and DNA fragmentation. Importantly, the n-butyl ester complex is more effective against leukemic patients' blood mononuclear cells relative to those from healthy control subjects, thus indicating a fairly selective antileukemic action of Ru(II)-based compounds.",
publisher = "Wiley-Blackwell, Malden",
journal = "ChemMedChem",
title = "Synthesis and in vitro Anticancer Activity of Ruthenium-Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-diacetate-Type Ligands",
volume = "6",
number = "10",
pages = "1884-1891",
doi = "10.1002/cmdc.201100232"
}

Savić, A., Dulović, M., Poljarević, J., Misirlić-Denčić, S., Jovanović, M., Bogdanović, A., Trajković, V. S., Sabo, T., Grgurić-Šipka, S.,& Marković, I.. (2011). Synthesis and in vitro Anticancer Activity of Ruthenium-Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-diacetate-Type Ligands. in ChemMedChem
Wiley-Blackwell, Malden., 6(10), 1884-1891.
https://doi.org/10.1002/cmdc.201100232

Savić A, Dulović M, Poljarević J, Misirlić-Denčić S, Jovanović M, Bogdanović A, Trajković VS, Sabo T, Grgurić-Šipka S, Marković I. Synthesis and in vitro Anticancer Activity of Ruthenium-Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-diacetate-Type Ligands. in ChemMedChem. 2011;6(10):1884-1891.
doi:10.1002/cmdc.201100232 .

Savić, Aleksandar, Dulović, Marija, Poljarević, Jelena, Misirlić-Denčić, Sonja, Jovanović, Maja, Bogdanović, Andrija, Trajković, Vladimir S., Sabo, Tibor, Grgurić-Šipka, Sanja, Marković, Ivanka, "Synthesis and in vitro Anticancer Activity of Ruthenium-Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-diacetate-Type Ligands" in ChemMedChem, 6, no. 10 (2011):1884-1891,
https://doi.org/10.1002/cmdc.201100232 . .