TY  - JOUR
AU  - Zmejkovski, Bojana
AU  - Pantelic, Nebojsa
AU  - Filipovic, Lana
AU  - Arandelovic, Sandra
AU  - Radulovic, Sinisa
AU  - Sabo, Tibor
AU  - Kaluđerović, Goran N.
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2132
AB  - Aims: Platinum(II) and platinum(IV) complexes [PtCln{(S,S)-(i-Am)(2)eddip}] (n = 2, 4: 1, 2, respectively; (S,S)-(i-Am)(2)eddip = O,O'-diisoamyl-(S,S)-ethylenediamine-N,N'-di-2-propanoate) were synthesized and characterized by elemental analysis, IR, H-1 and C-13 NMR spectroscopy and mass spectrometry. Method: Quantum chemical calculations were used to predict formed isomers of 1 and 2. Furthermore, reduction of 2 with ascorbic acid was followed by time-dependant C-13 NMR spectroscopy in order to enable assignation of the formed isomers for complex 1. In vitro cytotoxic activity was determined for 1 and 2 on a panel of five human tumor cell lines derived from cervix adenocarcinoma (HeLa), alveolar basal adenocarcinoma (A549), breast adenocarcinoma (MDA-453), colorectal cancer (LS 174), erythromyeloblastoid leukemia (K562), as well as one non-malignant human lung fibroblast cell line (MRC-5), using MTT assay. Result: Both complexes exhibited high (2 against K562: IC50 = 5.4 mu M), more active than cisplatin, to moderate activity (1). Both complexes caused considerable decrease of cell number in K562 cells in G1, S and G2 phases, concordantly increasing subpopulation in sub-G1 fraction. Morphological analysis of K562 cell death induced by platinum(II/IV) complexes indicate apoptosis.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Anti-Cancer Agents in Medicinal Chemistry
T1  - In Vitro Anticancer Evaluation of Platinum(II/IV) Complexes with Diisoamyl Ester of (S,S)-ethylenediamine-N,N'-di-2-propanoic Acid
VL  - 17
IS  - 8
SP  - 1136
EP  - 1143
DO  - 10.2174/1871520616666161207155634
ER  - 

@article{
author = "Zmejkovski, Bojana and Pantelic, Nebojsa and Filipovic, Lana and Arandelovic, Sandra and Radulovic, Sinisa and Sabo, Tibor and Kaluđerović, Goran N.",
year = "2017",
abstract = "Aims: Platinum(II) and platinum(IV) complexes [PtCln{(S,S)-(i-Am)(2)eddip}] (n = 2, 4: 1, 2, respectively; (S,S)-(i-Am)(2)eddip = O,O'-diisoamyl-(S,S)-ethylenediamine-N,N'-di-2-propanoate) were synthesized and characterized by elemental analysis, IR, H-1 and C-13 NMR spectroscopy and mass spectrometry. Method: Quantum chemical calculations were used to predict formed isomers of 1 and 2. Furthermore, reduction of 2 with ascorbic acid was followed by time-dependant C-13 NMR spectroscopy in order to enable assignation of the formed isomers for complex 1. In vitro cytotoxic activity was determined for 1 and 2 on a panel of five human tumor cell lines derived from cervix adenocarcinoma (HeLa), alveolar basal adenocarcinoma (A549), breast adenocarcinoma (MDA-453), colorectal cancer (LS 174), erythromyeloblastoid leukemia (K562), as well as one non-malignant human lung fibroblast cell line (MRC-5), using MTT assay. Result: Both complexes exhibited high (2 against K562: IC50 = 5.4 mu M), more active than cisplatin, to moderate activity (1). Both complexes caused considerable decrease of cell number in K562 cells in G1, S and G2 phases, concordantly increasing subpopulation in sub-G1 fraction. Morphological analysis of K562 cell death induced by platinum(II/IV) complexes indicate apoptosis.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Anti-Cancer Agents in Medicinal Chemistry",
title = "In Vitro Anticancer Evaluation of Platinum(II/IV) Complexes with Diisoamyl Ester of (S,S)-ethylenediamine-N,N'-di-2-propanoic Acid",
volume = "17",
number = "8",
pages = "1136-1143",
doi = "10.2174/1871520616666161207155634"
}

Zmejkovski, B., Pantelic, N., Filipovic, L., Arandelovic, S., Radulovic, S., Sabo, T.,& Kaluđerović, G. N.. (2017). In Vitro Anticancer Evaluation of Platinum(II/IV) Complexes with Diisoamyl Ester of (S,S)-ethylenediamine-N,N'-di-2-propanoic Acid. in Anti-Cancer Agents in Medicinal Chemistry
Bentham Science Publ Ltd, Sharjah., 17(8), 1136-1143.
https://doi.org/10.2174/1871520616666161207155634

Zmejkovski B, Pantelic N, Filipovic L, Arandelovic S, Radulovic S, Sabo T, Kaluđerović GN. In Vitro Anticancer Evaluation of Platinum(II/IV) Complexes with Diisoamyl Ester of (S,S)-ethylenediamine-N,N'-di-2-propanoic Acid. in Anti-Cancer Agents in Medicinal Chemistry. 2017;17(8):1136-1143.
doi:10.2174/1871520616666161207155634 .

Zmejkovski, Bojana, Pantelic, Nebojsa, Filipovic, Lana, Arandelovic, Sandra, Radulovic, Sinisa, Sabo, Tibor, Kaluđerović, Goran N., "In Vitro Anticancer Evaluation of Platinum(II/IV) Complexes with Diisoamyl Ester of (S,S)-ethylenediamine-N,N'-di-2-propanoic Acid" in Anti-Cancer Agents in Medicinal Chemistry, 17, no. 8 (2017):1136-1143,
https://doi.org/10.2174/1871520616666161207155634 . .

TY  - JOUR
AU  - Kuhn, Paul-Steffen
AU  - Cremer, Laura
AU  - Gavriluta, Anatolie
AU  - Jovanovic, Katarina K
AU  - Filipovic, Lana
AU  - Hummer, Alfred A
AU  - Buechel, Gabriel E
AU  - Dojčinović, Biljana
AU  - Meier, Samuel M
AU  - Rompel, Annette
AU  - Radulovic, Sinisa
AU  - Tommasino, Jean Bernard
AU  - Luneau, Dominique
AU  - Arion, Vladimir B
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1680
AB  - A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d-4f) metal complexes of the general formula (nBu(4)N)(5)[Ln{RuCl3(-ox)(NO)}(4)], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu(4)N)(2)[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by (CNMR)-C-13 spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)](2-) are coordinated to Y-III and Dy-III, respectively, with formation of [Ln{RuCl3(-ox)(NO)}(4)](5-) (Ln=Y, Dy). While Y-III is eight-coordinate in 2, Dy-III is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu(4)N(+) ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2-5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d-4f) analogues (nBu(4)N)(5)[Ln{OsCl3(ox)(NO)}(4)] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2-5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d-4f metal complexes 6-9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4M was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Chemistry-A European Journal
T1  - Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity
VL  - 21
IS  - 39
SP  - 13703
EP  - 13713
DO  - 10.1002/chem.201502026
ER  - 

@article{
author = "Kuhn, Paul-Steffen and Cremer, Laura and Gavriluta, Anatolie and Jovanovic, Katarina K and Filipovic, Lana and Hummer, Alfred A and Buechel, Gabriel E and Dojčinović, Biljana and Meier, Samuel M and Rompel, Annette and Radulovic, Sinisa and Tommasino, Jean Bernard and Luneau, Dominique and Arion, Vladimir B",
year = "2015",
abstract = "A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d-4f) metal complexes of the general formula (nBu(4)N)(5)[Ln{RuCl3(-ox)(NO)}(4)], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu(4)N)(2)[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by (CNMR)-C-13 spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)](2-) are coordinated to Y-III and Dy-III, respectively, with formation of [Ln{RuCl3(-ox)(NO)}(4)](5-) (Ln=Y, Dy). While Y-III is eight-coordinate in 2, Dy-III is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu(4)N(+) ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2-5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d-4f) analogues (nBu(4)N)(5)[Ln{OsCl3(ox)(NO)}(4)] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2-5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d-4f metal complexes 6-9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4M was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Chemistry-A European Journal",
title = "Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity",
volume = "21",
number = "39",
pages = "13703-13713",
doi = "10.1002/chem.201502026"
}

Kuhn, P., Cremer, L., Gavriluta, A., Jovanovic, K. K., Filipovic, L., Hummer, A. A., Buechel, G. E., Dojčinović, B., Meier, S. M., Rompel, A., Radulovic, S., Tommasino, J. B., Luneau, D.,& Arion, V. B.. (2015). Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity. in Chemistry-A European Journal
Wiley-V C H Verlag Gmbh, Weinheim., 21(39), 13703-13713.
https://doi.org/10.1002/chem.201502026

Kuhn P, Cremer L, Gavriluta A, Jovanovic KK, Filipovic L, Hummer AA, Buechel GE, Dojčinović B, Meier SM, Rompel A, Radulovic S, Tommasino JB, Luneau D, Arion VB. Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity. in Chemistry-A European Journal. 2015;21(39):13703-13713.
doi:10.1002/chem.201502026 .

Kuhn, Paul-Steffen, Cremer, Laura, Gavriluta, Anatolie, Jovanovic, Katarina K, Filipovic, Lana, Hummer, Alfred A, Buechel, Gabriel E, Dojčinović, Biljana, Meier, Samuel M, Rompel, Annette, Radulovic, Sinisa, Tommasino, Jean Bernard, Luneau, Dominique, Arion, Vladimir B, "Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity" in Chemistry-A European Journal, 21, no. 39 (2015):13703-13713,
https://doi.org/10.1002/chem.201502026 . .

TY  - JOUR
AU  - Savic, Aleksandar
AU  - Filipovic, Lana
AU  - Arandelovic, Sandra
AU  - Dojčinović, Biljana
AU  - Radulovic, Sinisa
AU  - Sabo, Tibor
AU  - Grgurić-Šipka, Sanja
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1593
AB  - Novel Pt(II) complexes of general formula [PtI2(L1-3)], (C1-C3): where L1-3 are isobutyl, n-pentyl and isopentyl esters of (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid has been synthesized and characterized by elemental analysis, UV/Vis, IR, (H-1, C-13 and HSQC, Pt) NMR spectroscopy and ESI mass spectrometry. Spectroscopic data and computational studies have shown the usual square planar coordination geometry of synthesized complexes, with coordination of ligands via nitrogen donor atoms. The cytotoxic activity of novel ligands and corresponding complexes were investigated on a palette of different cells line. Complexes C1-C3 exhibited activity comparable to cisplatin, with IC50 values (04) ranging from 4.6 +/- 0.6 to 17.2 +/- 2, and showed the highest potential in HeLa, LS-174 and EA.hy.926 cells. Ligands L1-L3 exhibited two- to four-times less activity than corresponding complexes. Analysis of the mode of action in HeLa cells, by ICP-MS study, showed markedly higher intracellular accumulation and DNA binding affinity of C1-C3 versus cisplatin, after 4 h and 20 h post-treatment. Annexin-V-FITC assay, flow cytometry and fluorescence microscopy study demonstrated occurrence of cell death through both apoptotic and necrotic changes. Tested complexes, at corresponding IC50 concentrations, caused considerable "sub-G1" peak, without other substantial alterations of cell cycle, while only Cl induced higher level of phosphatidylserine externalization (11.7%), comparing to ligand L1 (4.9%) and cisplatin (8.4%). Structure-activity comparison indicated variations of C1-C3 cytotoxicity, related to the drug/ligand lipophilicity (C log P value), while intracellular platinum content and DNA platination increased on increase of length and branching of ester chain, in sequence: Cl (isobutyl)  LT  C2 (n-pentyl)  LT  C3 (isopentyl).
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2  - European Journal of Medicinal Chemistry
T1  - Synthesis, characterization and cytotoxic activity of novel platinum(II) iodido complexes
VL  - 82
SP  - 372
EP  - 384
DO  - 10.1016/j.ejmech.2014.05.060
ER  - 

@article{
author = "Savic, Aleksandar and Filipovic, Lana and Arandelovic, Sandra and Dojčinović, Biljana and Radulovic, Sinisa and Sabo, Tibor and Grgurić-Šipka, Sanja",
year = "2014",
abstract = "Novel Pt(II) complexes of general formula [PtI2(L1-3)], (C1-C3): where L1-3 are isobutyl, n-pentyl and isopentyl esters of (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid has been synthesized and characterized by elemental analysis, UV/Vis, IR, (H-1, C-13 and HSQC, Pt) NMR spectroscopy and ESI mass spectrometry. Spectroscopic data and computational studies have shown the usual square planar coordination geometry of synthesized complexes, with coordination of ligands via nitrogen donor atoms. The cytotoxic activity of novel ligands and corresponding complexes were investigated on a palette of different cells line. Complexes C1-C3 exhibited activity comparable to cisplatin, with IC50 values (04) ranging from 4.6 +/- 0.6 to 17.2 +/- 2, and showed the highest potential in HeLa, LS-174 and EA.hy.926 cells. Ligands L1-L3 exhibited two- to four-times less activity than corresponding complexes. Analysis of the mode of action in HeLa cells, by ICP-MS study, showed markedly higher intracellular accumulation and DNA binding affinity of C1-C3 versus cisplatin, after 4 h and 20 h post-treatment. Annexin-V-FITC assay, flow cytometry and fluorescence microscopy study demonstrated occurrence of cell death through both apoptotic and necrotic changes. Tested complexes, at corresponding IC50 concentrations, caused considerable "sub-G1" peak, without other substantial alterations of cell cycle, while only Cl induced higher level of phosphatidylserine externalization (11.7%), comparing to ligand L1 (4.9%) and cisplatin (8.4%). Structure-activity comparison indicated variations of C1-C3 cytotoxicity, related to the drug/ligand lipophilicity (C log P value), while intracellular platinum content and DNA platination increased on increase of length and branching of ester chain, in sequence: Cl (isobutyl)  LT  C2 (n-pentyl)  LT  C3 (isopentyl).",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "Synthesis, characterization and cytotoxic activity of novel platinum(II) iodido complexes",
volume = "82",
pages = "372-384",
doi = "10.1016/j.ejmech.2014.05.060"
}

Savic, A., Filipovic, L., Arandelovic, S., Dojčinović, B., Radulovic, S., Sabo, T.,& Grgurić-Šipka, S.. (2014). Synthesis, characterization and cytotoxic activity of novel platinum(II) iodido complexes. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 82, 372-384.
https://doi.org/10.1016/j.ejmech.2014.05.060

Savic A, Filipovic L, Arandelovic S, Dojčinović B, Radulovic S, Sabo T, Grgurić-Šipka S. Synthesis, characterization and cytotoxic activity of novel platinum(II) iodido complexes. in European Journal of Medicinal Chemistry. 2014;82:372-384.
doi:10.1016/j.ejmech.2014.05.060 .

Savic, Aleksandar, Filipovic, Lana, Arandelovic, Sandra, Dojčinović, Biljana, Radulovic, Sinisa, Sabo, Tibor, Grgurić-Šipka, Sanja, "Synthesis, characterization and cytotoxic activity of novel platinum(II) iodido complexes" in European Journal of Medicinal Chemistry, 82 (2014):372-384,
https://doi.org/10.1016/j.ejmech.2014.05.060 . .