TY  - JOUR
AU  - Joksimović, Nenad
AU  - Petronijević, Jelena
AU  - Radisavljević, Snežana
AU  - Petrović, Biljana
AU  - Mihajlović, Kristina
AU  - Janković, Nenad
AU  - Milović, Emilija
AU  - Milivojević, Dušan
AU  - Ilić, Bojana
AU  - Đurić, Ana
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10518
AB  - Considering the urgency of finding a cure for vicious diseases such as tumors, we have synthesized and characterized a small series of new copper(ii) complexes with biologically important ligands such as acylpyruvate. In addition to this, we used another four copper(ii) complexes, with ligands of the same type to examine the antitumor potential. The antitumor potential of the copper(ii) complexes was examined on three tumor cell lines and one normal human cell line using the MTT assay. All seven tested complexes showed very good cytotoxic effects. Two copper complexes that showed the best antitumor potential were selected for further testing that showed the best potential for potential application in the future. The mechanism of activity of these complexes was examined in detail using tests such as cell cycle, ROS level, oxidative DNA damage, and proteins related to hypoxia analysis. In addition, we examined the binding abilities of these complexes with biomolecules (Guo, Ino, 5′-GMP, BSA, and DNA). The results showed that the tested compounds bind strongly to DNA molecules through intercalation. Also, it has been shown that the tested compounds adequately bind to the BSA molecule, which indicates an even greater potential for some future application of these compounds in clinical practice. © 2022 The Royal Society of Chemistry.
T2  - RSC Advances
T1  - Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study
VL  - 12
IS  - 47
SP  - 30501
EP  - 30513
DO  - 10.1039/d2ra05797b
ER  - 

@article{
author = "Joksimović, Nenad and Petronijević, Jelena and Radisavljević, Snežana and Petrović, Biljana and Mihajlović, Kristina and Janković, Nenad and Milović, Emilija and Milivojević, Dušan and Ilić, Bojana and Đurić, Ana",
year = "2022",
abstract = "Considering the urgency of finding a cure for vicious diseases such as tumors, we have synthesized and characterized a small series of new copper(ii) complexes with biologically important ligands such as acylpyruvate. In addition to this, we used another four copper(ii) complexes, with ligands of the same type to examine the antitumor potential. The antitumor potential of the copper(ii) complexes was examined on three tumor cell lines and one normal human cell line using the MTT assay. All seven tested complexes showed very good cytotoxic effects. Two copper complexes that showed the best antitumor potential were selected for further testing that showed the best potential for potential application in the future. The mechanism of activity of these complexes was examined in detail using tests such as cell cycle, ROS level, oxidative DNA damage, and proteins related to hypoxia analysis. In addition, we examined the binding abilities of these complexes with biomolecules (Guo, Ino, 5′-GMP, BSA, and DNA). The results showed that the tested compounds bind strongly to DNA molecules through intercalation. Also, it has been shown that the tested compounds adequately bind to the BSA molecule, which indicates an even greater potential for some future application of these compounds in clinical practice. © 2022 The Royal Society of Chemistry.",
journal = "RSC Advances",
title = "Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study",
volume = "12",
number = "47",
pages = "30501-30513",
doi = "10.1039/d2ra05797b"
}

Joksimović, N., Petronijević, J., Radisavljević, S., Petrović, B., Mihajlović, K., Janković, N., Milović, E., Milivojević, D., Ilić, B.,& Đurić, A.. (2022). Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study. in RSC Advances, 12(47), 30501-30513.
https://doi.org/10.1039/d2ra05797b

Joksimović N, Petronijević J, Radisavljević S, Petrović B, Mihajlović K, Janković N, Milović E, Milivojević D, Ilić B, Đurić A. Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study. in RSC Advances. 2022;12(47):30501-30513.
doi:10.1039/d2ra05797b .

Joksimović, Nenad, Petronijević, Jelena, Radisavljević, Snežana, Petrović, Biljana, Mihajlović, Kristina, Janković, Nenad, Milović, Emilija, Milivojević, Dušan, Ilić, Bojana, Đurić, Ana, "Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study" in RSC Advances, 12, no. 47 (2022):30501-30513,
https://doi.org/10.1039/d2ra05797b . .

TY  - JOUR
AU  - Radisavljević, Snežana
AU  - Ćoćić, Dušan
AU  - Jovanović, Snežana
AU  - Šmit, Biljana
AU  - Petković, Marijana
AU  - Milivojević, Nevena
AU  - Planojević, Nevena
AU  - Marković, Snežana D.
AU  - Petrović, Biljana V.
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8592
AB  - Abstract: In this study, we have synthesized a series of dinuclear and trinuclear gold(III) complexes of the general formula [Au2(N–N)Cl6] (1–3) for dinuclear and [Au3(N–N)2Cl8]+ (4–6) for trinuclear compounds, respectively, in which N–N is a bidentate ligand (1,4-diaminobutane; 1,6-diaminohexane or 1,8-diaminooctane). These complexes were characterized by elemental analysis, molar conductivity, and spectroscopic techniques (IR, UV–Vis, 1H NMR, ESI–MS). We performed DFT calculations to get insight into the geometry of the studies complexes. DNA-binding studies were performed by UV–Vis spectrophotometry and fluorescence spectroscopy. The results of competitive reactions between gold(III) complexes and ethidium bromide (EB) towards DNA have shown that selected complexes can displace EB from DNA-EB adduct. In addition, these experiments confirm that polynuclear gold(III) complexes interact with DNA covalently or via intercalation. Furthermore, high values of binding constants of gold(III) complexes towards bovine serum albumin (BSA) protein indicate good binding affinity. In addition, redox stability of complexes in the presence of DNA/BSA was confirmed by cyclic voltammetry. Results of the interactions between gold(III) complexes with DNA/BSA were discussed in reference to molecular docking data obtain by Molegro virtual docker. The cytotoxic activity of synthesized gold(III) complexes was evaluated on human breast cancer cell line (MDA-MB-231), human colorectal cancer cell line (HCT-116), and normal human lung fibroblast cell line (MRC-5). All complexes dose-dependently reduced cancer and normal cells viabilities, with significant cytotoxic effects (IC50 < 25 μM) for trinuclear gold(III) complexes (4, 5) on HCT-116 cells. Graphic abstract: [Figure not available: see fulltext.].
T2  - JBIC Journal of Biological Inorganic Chemistry
T1  - Synthesis, characterization, DFT study, DNA/BSA-binding affinity, and cytotoxicity of some dinuclear and trinuclear gold(III) complexes
VL  - 24
IS  - 7
SP  - 1057
EP  - 1076
DO  - 10.1007/s00775-019-01716-8
ER  - 

@article{
author = "Radisavljević, Snežana and Ćoćić, Dušan and Jovanović, Snežana and Šmit, Biljana and Petković, Marijana and Milivojević, Nevena and Planojević, Nevena and Marković, Snežana D. and Petrović, Biljana V.",
year = "2019",
abstract = "Abstract: In this study, we have synthesized a series of dinuclear and trinuclear gold(III) complexes of the general formula [Au2(N–N)Cl6] (1–3) for dinuclear and [Au3(N–N)2Cl8]+ (4–6) for trinuclear compounds, respectively, in which N–N is a bidentate ligand (1,4-diaminobutane; 1,6-diaminohexane or 1,8-diaminooctane). These complexes were characterized by elemental analysis, molar conductivity, and spectroscopic techniques (IR, UV–Vis, 1H NMR, ESI–MS). We performed DFT calculations to get insight into the geometry of the studies complexes. DNA-binding studies were performed by UV–Vis spectrophotometry and fluorescence spectroscopy. The results of competitive reactions between gold(III) complexes and ethidium bromide (EB) towards DNA have shown that selected complexes can displace EB from DNA-EB adduct. In addition, these experiments confirm that polynuclear gold(III) complexes interact with DNA covalently or via intercalation. Furthermore, high values of binding constants of gold(III) complexes towards bovine serum albumin (BSA) protein indicate good binding affinity. In addition, redox stability of complexes in the presence of DNA/BSA was confirmed by cyclic voltammetry. Results of the interactions between gold(III) complexes with DNA/BSA were discussed in reference to molecular docking data obtain by Molegro virtual docker. The cytotoxic activity of synthesized gold(III) complexes was evaluated on human breast cancer cell line (MDA-MB-231), human colorectal cancer cell line (HCT-116), and normal human lung fibroblast cell line (MRC-5). All complexes dose-dependently reduced cancer and normal cells viabilities, with significant cytotoxic effects (IC50 < 25 μM) for trinuclear gold(III) complexes (4, 5) on HCT-116 cells. Graphic abstract: [Figure not available: see fulltext.].",
journal = "JBIC Journal of Biological Inorganic Chemistry",
title = "Synthesis, characterization, DFT study, DNA/BSA-binding affinity, and cytotoxicity of some dinuclear and trinuclear gold(III) complexes",
volume = "24",
number = "7",
pages = "1057-1076",
doi = "10.1007/s00775-019-01716-8"
}

Radisavljević, S., Ćoćić, D., Jovanović, S., Šmit, B., Petković, M., Milivojević, N., Planojević, N., Marković, S. D.,& Petrović, B. V.. (2019). Synthesis, characterization, DFT study, DNA/BSA-binding affinity, and cytotoxicity of some dinuclear and trinuclear gold(III) complexes. in JBIC Journal of Biological Inorganic Chemistry, 24(7), 1057-1076.
https://doi.org/10.1007/s00775-019-01716-8

Radisavljević S, Ćoćić D, Jovanović S, Šmit B, Petković M, Milivojević N, Planojević N, Marković SD, Petrović BV. Synthesis, characterization, DFT study, DNA/BSA-binding affinity, and cytotoxicity of some dinuclear and trinuclear gold(III) complexes. in JBIC Journal of Biological Inorganic Chemistry. 2019;24(7):1057-1076.
doi:10.1007/s00775-019-01716-8 .

Radisavljević, Snežana, Ćoćić, Dušan, Jovanović, Snežana, Šmit, Biljana, Petković, Marijana, Milivojević, Nevena, Planojević, Nevena, Marković, Snežana D., Petrović, Biljana V., "Synthesis, characterization, DFT study, DNA/BSA-binding affinity, and cytotoxicity of some dinuclear and trinuclear gold(III) complexes" in JBIC Journal of Biological Inorganic Chemistry, 24, no. 7 (2019):1057-1076,
https://doi.org/10.1007/s00775-019-01716-8 . .

TY  - JOUR
AU  - Radisavljević, Snežana
AU  - Bratsos, Ioannis
AU  - Scheurer, Andreas
AU  - Korzekwa, Jana
AU  - Masnikosa, Romana
AU  - Tot, Aleksandar
AU  - Gligorijević, Nevenka N.
AU  - Radulović, Siniša S.
AU  - Rilak Simović, Ana
PY  - 2018
UR  - http://xlink.rsc.org/?DOI=C8DT02903B
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7894
AB  - With the aim of assessing whether Au(iii) compounds with pincer type ligands might be utilized as potential antitumor agents, three new monofunctional Au(iii) complexes of the general formula [Au(N-N'-N)Cl]Cl-2, where N-N'-N = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine (H2LtBu, 1), 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine (Me2LtBu, 2) or 2,6-bis((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine (Me-2*L, 3) were synthesized. All complexes were characterized by elemental analysis, spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR) and mass spectrometry (MALDI TOF MS). The chemical behavior of the complexes under physiological conditions was studied by UV-Vis spectroscopy, which showed that all compounds were remarkably stable and that the gold center remained in the 3+ oxidation state. The kinetics and the mechanism of the reaction of complexes 1-3 with guanine derivatives (i.e. guanosine (Guo) and guanosine-5-monophosphate (5-GMP)) and calf thymus DNA (CT DNA) were studied by stopped-flow spectroscopy. The three complexes displayed moderately different rate constants in their reactions with Guo, 5-GMP and CT DNA, which can be explained by the steric hindrance and sigma-donicity of the methyl substituent on the bis-pyrazolylpyridine fragment in complexes 2 and 3. The measured enthalpies and entropies of activation (Delta H-not equal > 0, Delta S-not equal < 0) supported an associative mechanism for the substitution process. The interaction of the newly synthesized complexes 1-3 with CT DNA was investigated by UV-Vis and fluorescence spectroscopy, and also by viscosity measurements, which all indicated that complexes 1-3 bound to CT DNA with moderate binding affinity (K-b = 1.6-5.7 x 10(3) M-1) and stabilized the duplex of CT DNA. Molecular docking indicated that complexes 1-3 interacted with DNA via intercalation. Complex 1 reduced the cell survival of all the investigated cell lines (A549, A375, and LS-174) with IC50 values being up to 20 mu M. We have shown that 1 induced perturbations of the cell cycle and led to apoptosis in human melanoma A375 cells. Complex 1 also affected the level of reactive oxygen species (ROS) in the same cells. However, pre-treatment of A375 cells with NAC (ROS scavenger) reversed the effect of 1 on their survival.
T2  - Dalton Transactions
T1  - New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity
VL  - 47
IS  - 38
SP  - 13696
EP  - 13712
DO  - 10.1039/C8DT02903B
ER  - 

@article{
author = "Radisavljević, Snežana and Bratsos, Ioannis and Scheurer, Andreas and Korzekwa, Jana and Masnikosa, Romana and Tot, Aleksandar and Gligorijević, Nevenka N. and Radulović, Siniša S. and Rilak Simović, Ana",
year = "2018",
abstract = "With the aim of assessing whether Au(iii) compounds with pincer type ligands might be utilized as potential antitumor agents, three new monofunctional Au(iii) complexes of the general formula [Au(N-N'-N)Cl]Cl-2, where N-N'-N = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine (H2LtBu, 1), 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine (Me2LtBu, 2) or 2,6-bis((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine (Me-2*L, 3) were synthesized. All complexes were characterized by elemental analysis, spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR) and mass spectrometry (MALDI TOF MS). The chemical behavior of the complexes under physiological conditions was studied by UV-Vis spectroscopy, which showed that all compounds were remarkably stable and that the gold center remained in the 3+ oxidation state. The kinetics and the mechanism of the reaction of complexes 1-3 with guanine derivatives (i.e. guanosine (Guo) and guanosine-5-monophosphate (5-GMP)) and calf thymus DNA (CT DNA) were studied by stopped-flow spectroscopy. The three complexes displayed moderately different rate constants in their reactions with Guo, 5-GMP and CT DNA, which can be explained by the steric hindrance and sigma-donicity of the methyl substituent on the bis-pyrazolylpyridine fragment in complexes 2 and 3. The measured enthalpies and entropies of activation (Delta H-not equal > 0, Delta S-not equal < 0) supported an associative mechanism for the substitution process. The interaction of the newly synthesized complexes 1-3 with CT DNA was investigated by UV-Vis and fluorescence spectroscopy, and also by viscosity measurements, which all indicated that complexes 1-3 bound to CT DNA with moderate binding affinity (K-b = 1.6-5.7 x 10(3) M-1) and stabilized the duplex of CT DNA. Molecular docking indicated that complexes 1-3 interacted with DNA via intercalation. Complex 1 reduced the cell survival of all the investigated cell lines (A549, A375, and LS-174) with IC50 values being up to 20 mu M. We have shown that 1 induced perturbations of the cell cycle and led to apoptosis in human melanoma A375 cells. Complex 1 also affected the level of reactive oxygen species (ROS) in the same cells. However, pre-treatment of A375 cells with NAC (ROS scavenger) reversed the effect of 1 on their survival.",
journal = "Dalton Transactions",
title = "New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity",
volume = "47",
number = "38",
pages = "13696-13712",
doi = "10.1039/C8DT02903B"
}

Radisavljević, S., Bratsos, I., Scheurer, A., Korzekwa, J., Masnikosa, R., Tot, A., Gligorijević, N. N., Radulović, S. S.,& Rilak Simović, A.. (2018). New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity. in Dalton Transactions, 47(38), 13696-13712.
https://doi.org/10.1039/C8DT02903B

Radisavljević S, Bratsos I, Scheurer A, Korzekwa J, Masnikosa R, Tot A, Gligorijević NN, Radulović SS, Rilak Simović A. New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity. in Dalton Transactions. 2018;47(38):13696-13712.
doi:10.1039/C8DT02903B .

Radisavljević, Snežana, Bratsos, Ioannis, Scheurer, Andreas, Korzekwa, Jana, Masnikosa, Romana, Tot, Aleksandar, Gligorijević, Nevenka N., Radulović, Siniša S., Rilak Simović, Ana, "New gold pincer-type complexes: synthesis, characterization, DNA binding studies and cytotoxicity" in Dalton Transactions, 47, no. 38 (2018):13696-13712,
https://doi.org/10.1039/C8DT02903B . .