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  - Lakić, Mladen
AU  - Sabo, Ljubica
AU  - Ristić, Slavica
AU  - Savić, Aleksandar
AU  - Petričević, Saša
AU  - Nikolić, Nadežda
AU  - Vukadinović, Aleksandar
AU  - Janković, Drina
AU  - Sabo, Tibor
AU  - Vranješ-Đurić, Sanja
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2045
AB  - The extensive development of radiopharmaceuticals towards early tumour detection and treatment has increased the demand for new ligands with higher tumour selectivity. Research has been done on the potential of the novel O,O'-diethylethylenediamine-N,N'-di-3-propanoate (L) ligand as a radionuclide vehicle for tumour targeting. Under alkaline conditions, L hydrolyses and produces half ester ligand (L') and diacid ligand (L"), with characteristic donor atom array N, N, O. Ligand L was successfully labelled with Tc-99m at pH=9 by coordination with the octahedral fac-[Tc-99m(CO)(3)(H2O)(3)](+) intermediate, forming the main radioproduct fac-[(TcL)-Tc-99m'(CO)(3)] (Tc1). The Tc-99m complex showed a low lipophilic character (log P = 0.48) and low binding affinity to human serum albumin (2.51 +/- 0.48%). In vitro stability studies in saline and human plasma, as well as challenge studies with cysteine and histidine, revealed high stability of the complex during 24 h. Biodistribution studies of Tc1 in female C57BL/6 mice bearing B16/F1 melanoma metastases showed significant tumour uptake: 9.81 +/- 1.19% ID g(-1) in the liver, 5.87 +/- 0.54% ID g(-1) in the lungs and 3.17 +/- 0.33% ID g(-1) in the ovary at 30 min post-injection. Favourable physicochemical properties, satisfactory in vitro/in vivo stability and biodistribution profile in the experimental metastatic melanoma model indicate the possible application of the radiolabelled ligand in tumour diagnosis. Copyright (C) 2015 John Wiley & Sons, Ltd.
PB  - Wiley, Hoboken
T2  - Applied Organometallic Chemistry
T1  - Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O '-diethylethylenediamine-N,N '-di-3-propanoate as potential tumour diagnostic agent
VL  - 30
IS  - 2
SP  - 81
EP  - 88
DO  - 10.1002/aoc.3401
ER  - 

@article{
author = "Lakić, Mladen and Sabo, Ljubica and Ristić, Slavica and Savić, Aleksandar and Petričević, Saša and Nikolić, Nadežda and Vukadinović, Aleksandar and Janković, Drina and Sabo, Tibor and Vranješ-Đurić, Sanja",
year = "2016",
abstract = "The extensive development of radiopharmaceuticals towards early tumour detection and treatment has increased the demand for new ligands with higher tumour selectivity. Research has been done on the potential of the novel O,O'-diethylethylenediamine-N,N'-di-3-propanoate (L) ligand as a radionuclide vehicle for tumour targeting. Under alkaline conditions, L hydrolyses and produces half ester ligand (L') and diacid ligand (L"), with characteristic donor atom array N, N, O. Ligand L was successfully labelled with Tc-99m at pH=9 by coordination with the octahedral fac-[Tc-99m(CO)(3)(H2O)(3)](+) intermediate, forming the main radioproduct fac-[(TcL)-Tc-99m'(CO)(3)] (Tc1). The Tc-99m complex showed a low lipophilic character (log P = 0.48) and low binding affinity to human serum albumin (2.51 +/- 0.48%). In vitro stability studies in saline and human plasma, as well as challenge studies with cysteine and histidine, revealed high stability of the complex during 24 h. Biodistribution studies of Tc1 in female C57BL/6 mice bearing B16/F1 melanoma metastases showed significant tumour uptake: 9.81 +/- 1.19% ID g(-1) in the liver, 5.87 +/- 0.54% ID g(-1) in the lungs and 3.17 +/- 0.33% ID g(-1) in the ovary at 30 min post-injection. Favourable physicochemical properties, satisfactory in vitro/in vivo stability and biodistribution profile in the experimental metastatic melanoma model indicate the possible application of the radiolabelled ligand in tumour diagnosis. Copyright (C) 2015 John Wiley & Sons, Ltd.",
publisher = "Wiley, Hoboken",
journal = "Applied Organometallic Chemistry",
title = "Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O '-diethylethylenediamine-N,N '-di-3-propanoate as potential tumour diagnostic agent",
volume = "30",
number = "2",
pages = "81-88",
doi = "10.1002/aoc.3401"
}

Lakić, M., Sabo, L., Ristić, S., Savić, A., Petričević, S., Nikolić, N., Vukadinović, A., Janković, D., Sabo, T.,& Vranješ-Đurić, S.. (2016). Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O '-diethylethylenediamine-N,N '-di-3-propanoate as potential tumour diagnostic agent. in Applied Organometallic Chemistry
Wiley, Hoboken., 30(2), 81-88.
https://doi.org/10.1002/aoc.3401

Lakić M, Sabo L, Ristić S, Savić A, Petričević S, Nikolić N, Vukadinović A, Janković D, Sabo T, Vranješ-Đurić S. Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O '-diethylethylenediamine-N,N '-di-3-propanoate as potential tumour diagnostic agent. in Applied Organometallic Chemistry. 2016;30(2):81-88.
doi:10.1002/aoc.3401 .

Lakić, Mladen, Sabo, Ljubica, Ristić, Slavica, Savić, Aleksandar, Petričević, Saša, Nikolić, Nadežda, Vukadinović, Aleksandar, Janković, Drina, Sabo, Tibor, Vranješ-Đurić, Sanja, "Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O '-diethylethylenediamine-N,N '-di-3-propanoate as potential tumour diagnostic agent" in Applied Organometallic Chemistry, 30, no. 2 (2016):81-88,
https://doi.org/10.1002/aoc.3401 . .