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 . .