TY  - JOUR
AU  - Rilak Simović, Ana
AU  - Masnikosa, Romana
AU  - Bratsos, Ioannis
AU  - Alessio, Enzo
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8433
AB  - In this review we summarize our work on development of Ru complexes with potential antitumor activity, which was performed over the last few years. In order to establish the structure-activity relationship for Ru(II) compounds, we have designed, synthesized and thoroughly studied several Ru(II) complexes, which were divided in three main groups: i) organometallic Ru(II)-arene complexes, ii) Ru(II) half-sandwich coordination complexes bearing neutral face-capping macrocyclic ligands, such as 1,4,7-trithiacyclononane ([9]aneS3) and 1,4,7-triazacyclononane ([9]aneN3), and iii) Ru(II)-polypyridyl complexes. Our most recent experiments moved toward synthesis, chemistry and reactivity of the heteronuclear ruthenium(II)/ferrocene complexes. The first part of the present review gives a brief overview of the structural features and anticancer activity of ruthenium complexes. The second part is focused mainly on the results obtained from the kinetic and mechanistic studies of the reactions between Ru(II) complexes and guanine derivatives, such as 9-methylguanine (9MeG), guanosine (Guo) and guanosine-5′-monophosphate (5′-GMP), as well as on structural characterization of the final products of these reactions. In the final part we deal with the reactions of Ru(II) complexes with DNA, which is widely accepted as a potential target for cytotoxic ruthenium compounds. We have also described the interactions of Ru(II) compounds with the most abundant transport proteins from human serum: human serum albumin (HSA) and transferrin (Tf). We believe that a systematic review of the aforementioned studies will not only contribute to the future development of ruthenium complexes as potential antitumor agents, but will also help to understand the potential toxicity of ruthenium-based drugs. © 2019 Elsevier B.V.
T2  - Coordination Chemistry Reviews
T1  - Chemistry and reactivity of ruthenium(II) complexes: DNA/protein binding mode and anticancer activity are related to the complex structure
VL  - 398
SP  - 113011
DO  - 10.1016/j.ccr.2019.07.008
ER  - 

@article{
author = "Rilak Simović, Ana and Masnikosa, Romana and Bratsos, Ioannis and Alessio, Enzo",
year = "2019",
abstract = "In this review we summarize our work on development of Ru complexes with potential antitumor activity, which was performed over the last few years. In order to establish the structure-activity relationship for Ru(II) compounds, we have designed, synthesized and thoroughly studied several Ru(II) complexes, which were divided in three main groups: i) organometallic Ru(II)-arene complexes, ii) Ru(II) half-sandwich coordination complexes bearing neutral face-capping macrocyclic ligands, such as 1,4,7-trithiacyclononane ([9]aneS3) and 1,4,7-triazacyclononane ([9]aneN3), and iii) Ru(II)-polypyridyl complexes. Our most recent experiments moved toward synthesis, chemistry and reactivity of the heteronuclear ruthenium(II)/ferrocene complexes. The first part of the present review gives a brief overview of the structural features and anticancer activity of ruthenium complexes. The second part is focused mainly on the results obtained from the kinetic and mechanistic studies of the reactions between Ru(II) complexes and guanine derivatives, such as 9-methylguanine (9MeG), guanosine (Guo) and guanosine-5′-monophosphate (5′-GMP), as well as on structural characterization of the final products of these reactions. In the final part we deal with the reactions of Ru(II) complexes with DNA, which is widely accepted as a potential target for cytotoxic ruthenium compounds. We have also described the interactions of Ru(II) compounds with the most abundant transport proteins from human serum: human serum albumin (HSA) and transferrin (Tf). We believe that a systematic review of the aforementioned studies will not only contribute to the future development of ruthenium complexes as potential antitumor agents, but will also help to understand the potential toxicity of ruthenium-based drugs. © 2019 Elsevier B.V.",
journal = "Coordination Chemistry Reviews",
title = "Chemistry and reactivity of ruthenium(II) complexes: DNA/protein binding mode and anticancer activity are related to the complex structure",
volume = "398",
pages = "113011",
doi = "10.1016/j.ccr.2019.07.008"
}

Rilak Simović, A., Masnikosa, R., Bratsos, I.,& Alessio, E.. (2019). Chemistry and reactivity of ruthenium(II) complexes: DNA/protein binding mode and anticancer activity are related to the complex structure. in Coordination Chemistry Reviews, 398, 113011.
https://doi.org/10.1016/j.ccr.2019.07.008

Rilak Simović A, Masnikosa R, Bratsos I, Alessio E. Chemistry and reactivity of ruthenium(II) complexes: DNA/protein binding mode and anticancer activity are related to the complex structure. in Coordination Chemistry Reviews. 2019;398:113011.
doi:10.1016/j.ccr.2019.07.008 .

Rilak Simović, Ana, Masnikosa, Romana, Bratsos, Ioannis, Alessio, Enzo, "Chemistry and reactivity of ruthenium(II) complexes: DNA/protein binding mode and anticancer activity are related to the complex structure" in Coordination Chemistry Reviews, 398 (2019):113011,
https://doi.org/10.1016/j.ccr.2019.07.008 . .

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 . .