TY  - JOUR
AU  - Ćoćić, Dušan
AU  - Jovanović, Snežana
AU  - Nišavić, Marija
AU  - Baskic, Dejan
AU  - Todorović, Danijela V.
AU  - Popovic, Suzana
AU  - Bugarčić, Živadin D.
AU  - Petrović, Biljana
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1758
AB  - Six new dinuclear Pd(II) complexes, [{Pd(2,2-bipy)Cl}(2)(mu-pz)](ClO4)2 (Pd1), [{Pd(dach)Cl}(2)(mu-pz)](ClO4)(2) (Pd2), [{Pd(en)Cl}(2)(mu-pz)] (ClO4)(2) (Pd3), [{Pd(2,2-bipy)Cl}(2)(mu-4,4-bipy)](ClO4)(2) (Pd4), [{Pd(dach)Cl}(2)(mu-4,4-bipy)] (ClO4)(2) (Pd5) and [{Pd(en)Cl-2(mu-4,4-bipy)](ClO4)(2) (Pd6) (where 2,2-bipy = 2,2-bipyridyl, pz = pyrazine, dach = trans-(+/-)-1,2-diaminocyclohexane, en = ethylenediamine, 4,4-bipy = 4,4-bipyridyl) have been synthesized and characterized by elemental microanalysis, IR, H-1 NMR and MALDI-TOF mass spectrometry. The pK(a) values of corresponding diaqua complexes were determined by spectrophotometric pH titration. Substitution reactions with thiourea (Tu), L-methionine (L-Met), L-cysteine (L-Cys), L-histidine (L-His) and guanosine-5-monophosphate (5-GMP) were studied under the pseudo-first order conditions at pH 7.2. Reactions of Pdl with Tu, L-Met and L-Cys were followed by decomposition of complexes, while structures of dinuclear complexes were preserved during the substitution with nitrogen donors. Interactions with calf-thymus DNA (CT DNA) were followed by absorption spectroscopy and fluorescence quenching measurements. All complexes can bind to CT-DNA exhibiting high intrinsic binding constants (K-b = 10(4)-10(5) M-1). Competitive studies with ethidium bromide (EB) have shown that complexes can displace DNA-bound EB. High values of binding constants towards bovine serum albumin protein (BSA) indicate good binding affinity. Finally, all complexes showed moderate to high cytotoxic activity against HeLa (human cervical epithelial carcinoma cell lines) and MDA-MB-231 (human breast epithelial carcinoma cell lines) tumor cell lines inducing apoptotic type cell death, whereas normal fibroblasts were significantly less sensitive. The impact on cell cycle of these cells was distinctive, where Pd4, Pd5 and Pd6 showed the most prominent effect arresting MDA-MB-231 (human lung fibroblast cell lines) cell in G1/S phase of cell cycle.
T2  - Journal of Inorganic Biochemistry
T1  - New dinuclear palladium(II) complexes: Studies of the nucleophilic substitution reactions, DNA/BSA interactions and cytotoxic activity
VL  - 175
SP  - 67
EP  - 79
DO  - 10.1016/j.jinorgbio.2017.07.009
ER  - 

@article{
author = "Ćoćić, Dušan and Jovanović, Snežana and Nišavić, Marija and Baskic, Dejan and Todorović, Danijela V. and Popovic, Suzana and Bugarčić, Živadin D. and Petrović, Biljana",
year = "2017",
abstract = "Six new dinuclear Pd(II) complexes, [{Pd(2,2-bipy)Cl}(2)(mu-pz)](ClO4)2 (Pd1), [{Pd(dach)Cl}(2)(mu-pz)](ClO4)(2) (Pd2), [{Pd(en)Cl}(2)(mu-pz)] (ClO4)(2) (Pd3), [{Pd(2,2-bipy)Cl}(2)(mu-4,4-bipy)](ClO4)(2) (Pd4), [{Pd(dach)Cl}(2)(mu-4,4-bipy)] (ClO4)(2) (Pd5) and [{Pd(en)Cl-2(mu-4,4-bipy)](ClO4)(2) (Pd6) (where 2,2-bipy = 2,2-bipyridyl, pz = pyrazine, dach = trans-(+/-)-1,2-diaminocyclohexane, en = ethylenediamine, 4,4-bipy = 4,4-bipyridyl) have been synthesized and characterized by elemental microanalysis, IR, H-1 NMR and MALDI-TOF mass spectrometry. The pK(a) values of corresponding diaqua complexes were determined by spectrophotometric pH titration. Substitution reactions with thiourea (Tu), L-methionine (L-Met), L-cysteine (L-Cys), L-histidine (L-His) and guanosine-5-monophosphate (5-GMP) were studied under the pseudo-first order conditions at pH 7.2. Reactions of Pdl with Tu, L-Met and L-Cys were followed by decomposition of complexes, while structures of dinuclear complexes were preserved during the substitution with nitrogen donors. Interactions with calf-thymus DNA (CT DNA) were followed by absorption spectroscopy and fluorescence quenching measurements. All complexes can bind to CT-DNA exhibiting high intrinsic binding constants (K-b = 10(4)-10(5) M-1). Competitive studies with ethidium bromide (EB) have shown that complexes can displace DNA-bound EB. High values of binding constants towards bovine serum albumin protein (BSA) indicate good binding affinity. Finally, all complexes showed moderate to high cytotoxic activity against HeLa (human cervical epithelial carcinoma cell lines) and MDA-MB-231 (human breast epithelial carcinoma cell lines) tumor cell lines inducing apoptotic type cell death, whereas normal fibroblasts were significantly less sensitive. The impact on cell cycle of these cells was distinctive, where Pd4, Pd5 and Pd6 showed the most prominent effect arresting MDA-MB-231 (human lung fibroblast cell lines) cell in G1/S phase of cell cycle.",
journal = "Journal of Inorganic Biochemistry",
title = "New dinuclear palladium(II) complexes: Studies of the nucleophilic substitution reactions, DNA/BSA interactions and cytotoxic activity",
volume = "175",
pages = "67-79",
doi = "10.1016/j.jinorgbio.2017.07.009"
}

Ćoćić, D., Jovanović, S., Nišavić, M., Baskic, D., Todorović, D. V., Popovic, S., Bugarčić, Ž. D.,& Petrović, B.. (2017). New dinuclear palladium(II) complexes: Studies of the nucleophilic substitution reactions, DNA/BSA interactions and cytotoxic activity. in Journal of Inorganic Biochemistry, 175, 67-79.
https://doi.org/10.1016/j.jinorgbio.2017.07.009

Ćoćić D, Jovanović S, Nišavić M, Baskic D, Todorović DV, Popovic S, Bugarčić ŽD, Petrović B. New dinuclear palladium(II) complexes: Studies of the nucleophilic substitution reactions, DNA/BSA interactions and cytotoxic activity. in Journal of Inorganic Biochemistry. 2017;175:67-79.
doi:10.1016/j.jinorgbio.2017.07.009 .

Ćoćić, Dušan, Jovanović, Snežana, Nišavić, Marija, Baskic, Dejan, Todorović, Danijela V., Popovic, Suzana, Bugarčić, Živadin D., Petrović, Biljana, "New dinuclear palladium(II) complexes: Studies of the nucleophilic substitution reactions, DNA/BSA interactions and cytotoxic activity" in Journal of Inorganic Biochemistry, 175 (2017):67-79,
https://doi.org/10.1016/j.jinorgbio.2017.07.009 . .

TY  - JOUR
AU  - Joksimović, Nenad
AU  - Baskic, Dejan
AU  - Popovic, Suzana
AU  - Zarić, Milan
AU  - Kosanić, Marijana
AU  - Ranković, Branislav
AU  - Stanojković, Tatjana P.
AU  - Novaković, Slađana B.
AU  - Davidovic, Goran
AU  - Bugarčič, Zorica M.
AU  - Janković, Nenad
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1269
AB  - A serie of novel square pyramidal copper(II) complexes [Cu(L)(2)H2O] (3a-d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4-hydroxy-3-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth micro-dilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL(-1)) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 mu g mL(-1). The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB-DNA complex through intercalation suggesting strong competition with EB [K-sv = (1.4 +/- 0.2) and (2.9 +/- 0.1) x 10(4) M-1, respectively]. K-sv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [K-a = (2.9 +/- 0.2) x 10(6) and (2.5 +/- 0.2) x 10(5) M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d- and 3e-BSA complexes. The obtained K-a values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells.
T2  - Dalton Transactions
T1  - Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate
VL  - 45
IS  - 38
SP  - 15067
EP  - 15077
DO  - 10.1039/c6dt02257j
ER  - 

@article{
author = "Joksimović, Nenad and Baskic, Dejan and Popovic, Suzana and Zarić, Milan and Kosanić, Marijana and Ranković, Branislav and Stanojković, Tatjana P. and Novaković, Slađana B. and Davidovic, Goran and Bugarčič, Zorica M. and Janković, Nenad",
year = "2016",
abstract = "A serie of novel square pyramidal copper(II) complexes [Cu(L)(2)H2O] (3a-d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4-hydroxy-3-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth micro-dilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL(-1)) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 mu g mL(-1). The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB-DNA complex through intercalation suggesting strong competition with EB [K-sv = (1.4 +/- 0.2) and (2.9 +/- 0.1) x 10(4) M-1, respectively]. K-sv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [K-a = (2.9 +/- 0.2) x 10(6) and (2.5 +/- 0.2) x 10(5) M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d- and 3e-BSA complexes. The obtained K-a values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells.",
journal = "Dalton Transactions",
title = "Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate",
volume = "45",
number = "38",
pages = "15067-15077",
doi = "10.1039/c6dt02257j"
}

Joksimović, N., Baskic, D., Popovic, S., Zarić, M., Kosanić, M., Ranković, B., Stanojković, T. P., Novaković, S. B., Davidovic, G., Bugarčič, Z. M.,& Janković, N.. (2016). Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate. in Dalton Transactions, 45(38), 15067-15077.
https://doi.org/10.1039/c6dt02257j

Joksimović N, Baskic D, Popovic S, Zarić M, Kosanić M, Ranković B, Stanojković TP, Novaković SB, Davidovic G, Bugarčič ZM, Janković N. Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate. in Dalton Transactions. 2016;45(38):15067-15077.
doi:10.1039/c6dt02257j .

Joksimović, Nenad, Baskic, Dejan, Popovic, Suzana, Zarić, Milan, Kosanić, Marijana, Ranković, Branislav, Stanojković, Tatjana P., Novaković, Slađana B., Davidovic, Goran, Bugarčič, Zorica M., Janković, Nenad, "Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate" in Dalton Transactions, 45, no. 38 (2016):15067-15077,
https://doi.org/10.1039/c6dt02257j . .