TY  - JOUR
AU  - Jovanović-Stević, Snežana
AU  - Radisavljević, Snežana
AU  - Scheurer, Andreas
AU  - Ćoćić, Dušan
AU  - Šmit, Biljana
AU  - Petković, Marijana
AU  - Živanović, Marko N.
AU  - Virijević, Katarina
AU  - Petrović, Biljana
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13318
AB  - Four new complexes of Pt(II) and Pd(II), [Pd(L1)Cl]Cl 1, [Pd(L2)Cl]Cl 2, [Pt(L1)Cl]Cl 3 and [Pt(L2)Cl]Cl 4 (where L1 = 2,6-bis(5,6-diphenyl-1,2,4-triazin-3-yl)pyridine and L2 = 2,6-bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine), were synthesized. Characterization of the complexes was performed using elemental analysis, IR, 1H NMR spectroscopy and MALDI-TOF mass spectrometry. The substitution reactions of 1-4 complexes with L-methionine (L-met), L-cysteine (L-cys) and guanosine-5'-monophosphate (5'-GMP), were studied spectrophotometrically at physiological conditions. Complexes with ligand L1 (1 or 3) were more reactive than those with ligand L2 (2 or 4) by a factor ranging up to 1.57 and 3.71, respectively. The order of reactivity of the nucleophiles was: L-met > L-cys > 5'-GMP. The interactions of complexes with calf thymus-DNA (CT-DNA) and human serum albumin (HSA) were studied by Uv-Vis absorption and fluorescence emission spectroscopy. Competitive binding studies with intercalative agent ethidium bromide (EB) and minor groove binder Hoechst 33258 were performed as well. All studied complexes can interact with DNA through the intercalation and minor groove binding, where the latter was preferred. The binding constants (103 and 104 M-1) for the interaction of complexes with HSA indicate the moderate binding affinity of complexes 1-4 to protein. The trends in the experimental results of binding studies between complexes 3 and 4 with DNA and HSA were compared to those obtained from the molecular docking study. Biological evaluation of cytotoxicity of 1 and 2 on HCT-116 and MDA-MB-231 cell lines showed significant cytotoxic and prooxidative character, while 2 also exerted extraordinary selectivity towards colon cancer in comparison to breast cancer cells. The nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity of bis(triazinyl)pyridine complexes of Pt(II) and Pd(II) were studied.
T2  - JBIC Journal of Biological Inorganic Chemistry
T1  - Bis(triazinyl)pyridine complexes of Pt(II) and Pd(II): studies of the nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity
VL  - 26
IS  - 5
SP  - 625
EP  - 637
DO  - 10.1007/s00775-021-01879-3
ER  - 

@article{
author = "Jovanović-Stević, Snežana and Radisavljević, Snežana and Scheurer, Andreas and Ćoćić, Dušan and Šmit, Biljana and Petković, Marijana and Živanović, Marko N. and Virijević, Katarina and Petrović, Biljana",
year = "2021",
abstract = "Four new complexes of Pt(II) and Pd(II), [Pd(L1)Cl]Cl 1, [Pd(L2)Cl]Cl 2, [Pt(L1)Cl]Cl 3 and [Pt(L2)Cl]Cl 4 (where L1 = 2,6-bis(5,6-diphenyl-1,2,4-triazin-3-yl)pyridine and L2 = 2,6-bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine), were synthesized. Characterization of the complexes was performed using elemental analysis, IR, 1H NMR spectroscopy and MALDI-TOF mass spectrometry. The substitution reactions of 1-4 complexes with L-methionine (L-met), L-cysteine (L-cys) and guanosine-5'-monophosphate (5'-GMP), were studied spectrophotometrically at physiological conditions. Complexes with ligand L1 (1 or 3) were more reactive than those with ligand L2 (2 or 4) by a factor ranging up to 1.57 and 3.71, respectively. The order of reactivity of the nucleophiles was: L-met > L-cys > 5'-GMP. The interactions of complexes with calf thymus-DNA (CT-DNA) and human serum albumin (HSA) were studied by Uv-Vis absorption and fluorescence emission spectroscopy. Competitive binding studies with intercalative agent ethidium bromide (EB) and minor groove binder Hoechst 33258 were performed as well. All studied complexes can interact with DNA through the intercalation and minor groove binding, where the latter was preferred. The binding constants (103 and 104 M-1) for the interaction of complexes with HSA indicate the moderate binding affinity of complexes 1-4 to protein. The trends in the experimental results of binding studies between complexes 3 and 4 with DNA and HSA were compared to those obtained from the molecular docking study. Biological evaluation of cytotoxicity of 1 and 2 on HCT-116 and MDA-MB-231 cell lines showed significant cytotoxic and prooxidative character, while 2 also exerted extraordinary selectivity towards colon cancer in comparison to breast cancer cells. The nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity of bis(triazinyl)pyridine complexes of Pt(II) and Pd(II) were studied.",
journal = "JBIC Journal of Biological Inorganic Chemistry",
title = "Bis(triazinyl)pyridine complexes of Pt(II) and Pd(II): studies of the nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity",
volume = "26",
number = "5",
pages = "625-637",
doi = "10.1007/s00775-021-01879-3"
}

Jovanović-Stević, S., Radisavljević, S., Scheurer, A., Ćoćić, D., Šmit, B., Petković, M., Živanović, M. N., Virijević, K.,& Petrović, B.. (2021). Bis(triazinyl)pyridine complexes of Pt(II) and Pd(II): studies of the nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity. in JBIC Journal of Biological Inorganic Chemistry, 26(5), 625-637.
https://doi.org/10.1007/s00775-021-01879-3

Jovanović-Stević S, Radisavljević S, Scheurer A, Ćoćić D, Šmit B, Petković M, Živanović MN, Virijević K, Petrović B. Bis(triazinyl)pyridine complexes of Pt(II) and Pd(II): studies of the nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity. in JBIC Journal of Biological Inorganic Chemistry. 2021;26(5):625-637.
doi:10.1007/s00775-021-01879-3 .

Jovanović-Stević, Snežana, Radisavljević, Snežana, Scheurer, Andreas, Ćoćić, Dušan, Šmit, Biljana, Petković, Marijana, Živanović, Marko N., Virijević, Katarina, Petrović, Biljana, "Bis(triazinyl)pyridine complexes of Pt(II) and Pd(II): studies of the nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity" in JBIC Journal of Biological Inorganic Chemistry, 26, no. 5 (2021):625-637,
https://doi.org/10.1007/s00775-021-01879-3 . .

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 . .