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  - Trifunović, Snežana S.
AU  - Isaković, Anđelka M.
AU  - Isaković, Aleksandra J.
AU  - Vučković, Ivan M.
AU  - Mandić, Boris
AU  - Novaković, Miroslav M.
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan M.
AU  - Trajković, Vladimir S.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1511
AB  - Further phytochemical investigation of the aerial parts of Achillea clavennae has resulted in the isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and the iso-seco-guaianolide 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known compounds were also found, of which 9-acetoxycanin (5), sintenin (6), and oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were elucidated by combined spectroscopic methods (1D and 2DNMR, HRESIMS, CIMS, and FTIR). While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Planta Medica
T1  - Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae
VL  - 80
IS  - 4
SP  - 297
EP  - 305
DO  - 10.1055/s-0033-1360312
ER  - 

@article{
author = "Trifunović, Snežana S. and Isaković, Anđelka M. and Isaković, Aleksandra J. and Vučković, Ivan M. and Mandić, Boris and Novaković, Miroslav M. and Vajs, Vlatka and Milosavljević, Slobodan M. and Trajković, Vladimir S.",
year = "2014",
abstract = "Further phytochemical investigation of the aerial parts of Achillea clavennae has resulted in the isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and the iso-seco-guaianolide 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known compounds were also found, of which 9-acetoxycanin (5), sintenin (6), and oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were elucidated by combined spectroscopic methods (1D and 2DNMR, HRESIMS, CIMS, and FTIR). While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Planta Medica",
title = "Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae",
volume = "80",
number = "4",
pages = "297-305",
doi = "10.1055/s-0033-1360312"
}

Trifunović, S. S., Isaković, A. M., Isaković, A. J., Vučković, I. M., Mandić, B., Novaković, M. M., Vajs, V., Milosavljević, S. M.,& Trajković, V. S.. (2014). Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae. in Planta Medica
Georg Thieme Verlag Kg, Stuttgart., 80(4), 297-305.
https://doi.org/10.1055/s-0033-1360312

Trifunović SS, Isaković AM, Isaković AJ, Vučković IM, Mandić B, Novaković MM, Vajs V, Milosavljević SM, Trajković VS. Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae. in Planta Medica. 2014;80(4):297-305.
doi:10.1055/s-0033-1360312 .

Trifunović, Snežana S., Isaković, Anđelka M., Isaković, Aleksandra J., Vučković, Ivan M., Mandić, Boris, Novaković, Miroslav M., Vajs, Vlatka, Milosavljević, Slobodan M., Trajković, Vladimir S., "Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae" in Planta Medica, 80, no. 4 (2014):297-305,
https://doi.org/10.1055/s-0033-1360312 . .

TY  - JOUR
AU  - Trifunović, Snežana S.
AU  - Isaković, Anđelka M.
AU  - Isaković, Aleksandra J.
AU  - Vučković, Ivan M.
AU  - Mandić, Boris
AU  - Novaković, Miroslav M.
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan M.
AU  - Trajković, Vladimir S.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2816
AB  - Further phytochemical investigation into the aerial parts of Achillea clavennae has resulted in the 3 
isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and 4 
the iso-seco-guaianolide, 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known 5 
compounds were also found in this plant species, of which 9 α -acetoxycanin (5), sintenin (6) and 6 
oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were 7 
elucidated by combined spectroscopic methods (1D and 2D NMR, HRESIMS, CIMS, FTIR). 8 
While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-9 
seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone 10 
apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.
PB  - Georg Thieme Verlag
T2  - Planta medica
T1  - Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae
VL  - 80
IS  - 4
SP  - 275
EP  - 305
DO  - 10.1055/s-0033-1360312
ER  - 

@article{
author = "Trifunović, Snežana S. and Isaković, Anđelka M. and Isaković, Aleksandra J. and Vučković, Ivan M. and Mandić, Boris and Novaković, Miroslav M. and Vajs, Vlatka and Milosavljević, Slobodan M. and Trajković, Vladimir S.",
year = "2014",
abstract = "Further phytochemical investigation into the aerial parts of Achillea clavennae has resulted in the 3 
isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and 4 
the iso-seco-guaianolide, 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known 5 
compounds were also found in this plant species, of which 9 α -acetoxycanin (5), sintenin (6) and 6 
oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were 7 
elucidated by combined spectroscopic methods (1D and 2D NMR, HRESIMS, CIMS, FTIR). 8 
While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-9 
seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone 10 
apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.",
publisher = "Georg Thieme Verlag",
journal = "Planta medica",
title = "Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae",
volume = "80",
number = "4",
pages = "275-305",
doi = "10.1055/s-0033-1360312"
}

Trifunović, S. S., Isaković, A. M., Isaković, A. J., Vučković, I. M., Mandić, B., Novaković, M. M., Vajs, V., Milosavljević, S. M.,& Trajković, V. S.. (2014). Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae. in Planta medica
Georg Thieme Verlag., 80(4), 275-305.
https://doi.org/10.1055/s-0033-1360312

Trifunović SS, Isaković AM, Isaković AJ, Vučković IM, Mandić B, Novaković MM, Vajs V, Milosavljević SM, Trajković VS. Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae. in Planta medica. 2014;80(4):275-305.
doi:10.1055/s-0033-1360312 .

Trifunović, Snežana S., Isaković, Anđelka M., Isaković, Aleksandra J., Vučković, Ivan M., Mandić, Boris, Novaković, Miroslav M., Vajs, Vlatka, Milosavljević, Slobodan M., Trajković, Vladimir S., "Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae" in Planta medica, 80, no. 4 (2014):275-305,
https://doi.org/10.1055/s-0033-1360312 . .

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 . .