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  - Nišavić, Marija
AU  - Stoiljković, Milovan
AU  - Crnolatac, Ivo
AU  - Milošević, Maja
AU  - Rilak, Ana
AU  - Masnikosa, Romana
PY  - 2018
UR  - http://linkinghub.elsevier.com/retrieve/pii/S1878535216301198
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7665
AB  - Three coordination compounds of ruthenium(II), belonging to a recently synthesised series of water-soluble compounds of general formula mer-{[}Ru(L3)(N-N) Cl] Cl, where L3 = 4'-chloro2,2': 6', 200-terpyridine (Cl-tpy), N-N= ethylenediamine (en), 1,2-diaminocyclohexane (dach) or 2,2'bipyridine (bpy), have shown strong binding to calf thymus DNA and moderate in vitro cytotoxicity towards cancer cell lines. Knowing that serum proteins play a crucial role in the transport and deactivation of ruthenium drugs, we have conducted a detailed study of their interactions with two major metal-transporting serum proteins, albumin and transferrin, and it is presented herein. Ruthenated protein adducts were formed with various concentrations of the three compounds and then separated from the unbound portions by ultrafiltration through 10 kDa cut-off centrifugal filter units. The stoichiometry of binding was determined using inductively coupled plasma optical emission spectrometry. One mol of albumin bound up to 7, 8.5 and 1.5 mol of compound 1 ({[}Ru(Cltpy)(en) Cl]{[}Cl]), 2 ({[}Ru(Cl-tpy)(dach) Cl]{[}Cl] and 3 ({[}Ru(Cl-tpy)(bpy) Cl]{[}Cl]), respectively. One mol of transferrin bound up to 3, 3.5 and 0.4 mol of 1, 2 and 3, respectively. The affinity of albumin and transferrin for the three ruthenium compounds was evaluated using fluorescence quenching. The binding constants for 1 and 2 lay within the range 10(4) -10(5) M - 1, suggesting moderate-to-strong attachment to albumin. Both compounds showed much lower affinity for transferrin (10(2) -10(3) M - 1). Compound 3 bound weakly to each studied protein. High resolution ESI qTOF mass spectra of albumin before and after binding of 1 revealed the high stoichiometry of binding. Although the binding of the compounds 1-3 to albumin and transferrin did not affect proteins' secondary structure much, their tertiary structures underwent some alterations, as deduced from the circular dichroism study. Changes in the stability of albumin, after binding to compounds 1-3 were examined by differential scanning calorimetry. (C) 2016 The Authors. Production and hosting by Elsevier B. V. on behalf of King Saud University. This is an open access article under theCCBY-NC-NDlicense.
T2  - Arabian Journal of Chemistry
T1  - Highly water-soluble ruthenium(II) terpyridine coordination compounds form stable adducts with blood-borne metal transporting proteins
VL  - 11
IS  - 3
SP  - 291
EP  - 304
DO  - 10.1016/j.arabjc.2016.07.021
ER  - 

@article{
author = "Nišavić, Marija and Stoiljković, Milovan and Crnolatac, Ivo and Milošević, Maja and Rilak, Ana and Masnikosa, Romana",
year = "2018",
abstract = "Three coordination compounds of ruthenium(II), belonging to a recently synthesised series of water-soluble compounds of general formula mer-{[}Ru(L3)(N-N) Cl] Cl, where L3 = 4'-chloro2,2': 6', 200-terpyridine (Cl-tpy), N-N= ethylenediamine (en), 1,2-diaminocyclohexane (dach) or 2,2'bipyridine (bpy), have shown strong binding to calf thymus DNA and moderate in vitro cytotoxicity towards cancer cell lines. Knowing that serum proteins play a crucial role in the transport and deactivation of ruthenium drugs, we have conducted a detailed study of their interactions with two major metal-transporting serum proteins, albumin and transferrin, and it is presented herein. Ruthenated protein adducts were formed with various concentrations of the three compounds and then separated from the unbound portions by ultrafiltration through 10 kDa cut-off centrifugal filter units. The stoichiometry of binding was determined using inductively coupled plasma optical emission spectrometry. One mol of albumin bound up to 7, 8.5 and 1.5 mol of compound 1 ({[}Ru(Cltpy)(en) Cl]{[}Cl]), 2 ({[}Ru(Cl-tpy)(dach) Cl]{[}Cl] and 3 ({[}Ru(Cl-tpy)(bpy) Cl]{[}Cl]), respectively. One mol of transferrin bound up to 3, 3.5 and 0.4 mol of 1, 2 and 3, respectively. The affinity of albumin and transferrin for the three ruthenium compounds was evaluated using fluorescence quenching. The binding constants for 1 and 2 lay within the range 10(4) -10(5) M - 1, suggesting moderate-to-strong attachment to albumin. Both compounds showed much lower affinity for transferrin (10(2) -10(3) M - 1). Compound 3 bound weakly to each studied protein. High resolution ESI qTOF mass spectra of albumin before and after binding of 1 revealed the high stoichiometry of binding. Although the binding of the compounds 1-3 to albumin and transferrin did not affect proteins' secondary structure much, their tertiary structures underwent some alterations, as deduced from the circular dichroism study. Changes in the stability of albumin, after binding to compounds 1-3 were examined by differential scanning calorimetry. (C) 2016 The Authors. Production and hosting by Elsevier B. V. on behalf of King Saud University. This is an open access article under theCCBY-NC-NDlicense.",
journal = "Arabian Journal of Chemistry",
title = "Highly water-soluble ruthenium(II) terpyridine coordination compounds form stable adducts with blood-borne metal transporting proteins",
volume = "11",
number = "3",
pages = "291-304",
doi = "10.1016/j.arabjc.2016.07.021"
}

Nišavić, M., Stoiljković, M., Crnolatac, I., Milošević, M., Rilak, A.,& Masnikosa, R.. (2018). Highly water-soluble ruthenium(II) terpyridine coordination compounds form stable adducts with blood-borne metal transporting proteins. in Arabian Journal of Chemistry, 11(3), 291-304.
https://doi.org/10.1016/j.arabjc.2016.07.021

Nišavić M, Stoiljković M, Crnolatac I, Milošević M, Rilak A, Masnikosa R. Highly water-soluble ruthenium(II) terpyridine coordination compounds form stable adducts with blood-borne metal transporting proteins. in Arabian Journal of Chemistry. 2018;11(3):291-304.
doi:10.1016/j.arabjc.2016.07.021 .

Nišavić, Marija, Stoiljković, Milovan, Crnolatac, Ivo, Milošević, Maja, Rilak, Ana, Masnikosa, Romana, "Highly water-soluble ruthenium(II) terpyridine coordination compounds form stable adducts with blood-borne metal transporting proteins" in Arabian Journal of Chemistry, 11, no. 3 (2018):291-304,
https://doi.org/10.1016/j.arabjc.2016.07.021 . .

TY  - JOUR
AU  - Milutinović, Milan M.
AU  - Čanović, Petar P.
AU  - Stevanović, Dragana D.
AU  - Masnikosa, Romana
AU  - Vraneš, Milan
AU  - Tot, Aleksandar
AU  - Zarić, Milan M.
AU  - Marković-Simović, Bojana
AU  - Misirkić-Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Savić, Maja
AU  - Jakovljević, Vladimir Lj.
AU  - Trajković, Vladimir S.
AU  - Volarević, Vladislav
AU  - Kanjevac, Tatjana
AU  - Rilak Simović, Ana
PY  - 2018
UR  - http://pubs.acs.org/doi/10.1021/acs.organomet.8b00604
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7967
AB  - The two new heterometallic Ru(II)-tpy/ferrocene complexes [Ru(tpy)Cl2(mtefc)] (1) and [Ru(tpy)Cl2(mtpfc)] (2) (where tpy = 2,2′:6′,2′′-terpyridine, mtefc = (2-(methylthio)ethyl)ferrocene, and mtpfc = (3-(methylthio)propyl)ferrocene) have been synthesized and then characterized through elemental analysis, followed by various spectroscopic (IR, UV-vis, 1D and 2D NMR) and mass spectrometric techniques (MALDI TOF and ESI Q-TOF MS). UV-vis and fluorescence spectroscopy and viscometry were employed to study the interactions of the complexes 1 and 2 with calf thymus DNA. Both 1 and 2 expelled ethidium bromide (EB) from the EB/DNA complex (Ksv = (1.5-1.8) × 104 M-1), which suggested that the complexes intercalated into the double helix of DNA. Both complexes strongly quenched the fluorescence of tryptophan residues in serum albumin through both static and dynamic quenching. Molecular docking confirmed the intercalative mode of complex interaction with DNA. The docking results implied that 1 and 2 interacted with hydrophobic residues of albumin, particularly with those lying in the proximity of Tyr 160. We here demonstrate the high cytotoxic potential of complexes 1 and 2 against the breast cancer cells that originated either from humans (MDA-MB-231) or from mice (4T1), with apoptosis being the main mechanism of complex-induced cell death. It is worth noting that both complexes promoted activation of innate and acquired antitumor immunity, which contributed to the reduced growth and progression of mammary carcinoma in vivo. Copyright © 2018 American Chemical Society.
T2  - Organometallics
T1  - Newly Synthesized Heteronuclear Ruthenium(II)/Ferrocene Complexes Suppress the Growth of Mammary Carcinoma in 4T1-Treated BALB/c Mice by Promoting Activation of Antitumor Immunity
VL  - 37
IS  - 22
SP  - 4250
EP  - 4266
DO  - 10.1021/acs.organomet.8b00604
ER  - 

@article{
author = "Milutinović, Milan M. and Čanović, Petar P. and Stevanović, Dragana D. and Masnikosa, Romana and Vraneš, Milan and Tot, Aleksandar and Zarić, Milan M. and Marković-Simović, Bojana and Misirkić-Marjanović, Maja and Vučićević, Ljubica and Savić, Maja and Jakovljević, Vladimir Lj. and Trajković, Vladimir S. and Volarević, Vladislav and Kanjevac, Tatjana and Rilak Simović, Ana",
year = "2018",
abstract = "The two new heterometallic Ru(II)-tpy/ferrocene complexes [Ru(tpy)Cl2(mtefc)] (1) and [Ru(tpy)Cl2(mtpfc)] (2) (where tpy = 2,2′:6′,2′′-terpyridine, mtefc = (2-(methylthio)ethyl)ferrocene, and mtpfc = (3-(methylthio)propyl)ferrocene) have been synthesized and then characterized through elemental analysis, followed by various spectroscopic (IR, UV-vis, 1D and 2D NMR) and mass spectrometric techniques (MALDI TOF and ESI Q-TOF MS). UV-vis and fluorescence spectroscopy and viscometry were employed to study the interactions of the complexes 1 and 2 with calf thymus DNA. Both 1 and 2 expelled ethidium bromide (EB) from the EB/DNA complex (Ksv = (1.5-1.8) × 104 M-1), which suggested that the complexes intercalated into the double helix of DNA. Both complexes strongly quenched the fluorescence of tryptophan residues in serum albumin through both static and dynamic quenching. Molecular docking confirmed the intercalative mode of complex interaction with DNA. The docking results implied that 1 and 2 interacted with hydrophobic residues of albumin, particularly with those lying in the proximity of Tyr 160. We here demonstrate the high cytotoxic potential of complexes 1 and 2 against the breast cancer cells that originated either from humans (MDA-MB-231) or from mice (4T1), with apoptosis being the main mechanism of complex-induced cell death. It is worth noting that both complexes promoted activation of innate and acquired antitumor immunity, which contributed to the reduced growth and progression of mammary carcinoma in vivo. Copyright © 2018 American Chemical Society.",
journal = "Organometallics",
title = "Newly Synthesized Heteronuclear Ruthenium(II)/Ferrocene Complexes Suppress the Growth of Mammary Carcinoma in 4T1-Treated BALB/c Mice by Promoting Activation of Antitumor Immunity",
volume = "37",
number = "22",
pages = "4250-4266",
doi = "10.1021/acs.organomet.8b00604"
}

Milutinović, M. M., Čanović, P. P., Stevanović, D. D., Masnikosa, R., Vraneš, M., Tot, A., Zarić, M. M., Marković-Simović, B., Misirkić-Marjanović, M., Vučićević, L., Savić, M., Jakovljević, V. Lj., Trajković, V. S., Volarević, V., Kanjevac, T.,& Rilak Simović, A.. (2018). Newly Synthesized Heteronuclear Ruthenium(II)/Ferrocene Complexes Suppress the Growth of Mammary Carcinoma in 4T1-Treated BALB/c Mice by Promoting Activation of Antitumor Immunity. in Organometallics, 37(22), 4250-4266.
https://doi.org/10.1021/acs.organomet.8b00604

Milutinović MM, Čanović PP, Stevanović DD, Masnikosa R, Vraneš M, Tot A, Zarić MM, Marković-Simović B, Misirkić-Marjanović M, Vučićević L, Savić M, Jakovljević VL, Trajković VS, Volarević V, Kanjevac T, Rilak Simović A. Newly Synthesized Heteronuclear Ruthenium(II)/Ferrocene Complexes Suppress the Growth of Mammary Carcinoma in 4T1-Treated BALB/c Mice by Promoting Activation of Antitumor Immunity. in Organometallics. 2018;37(22):4250-4266.
doi:10.1021/acs.organomet.8b00604 .

Milutinović, Milan M., Čanović, Petar P., Stevanović, Dragana D., Masnikosa, Romana, Vraneš, Milan, Tot, Aleksandar, Zarić, Milan M., Marković-Simović, Bojana, Misirkić-Marjanović, Maja, Vučićević, Ljubica, Savić, Maja, Jakovljević, Vladimir Lj., Trajković, Vladimir S., Volarević, Vladislav, Kanjevac, Tatjana, Rilak Simović, Ana, "Newly Synthesized Heteronuclear Ruthenium(II)/Ferrocene Complexes Suppress the Growth of Mammary Carcinoma in 4T1-Treated BALB/c Mice by Promoting Activation of Antitumor Immunity" in Organometallics, 37, no. 22 (2018):4250-4266,
https://doi.org/10.1021/acs.organomet.8b00604 . .

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 . .

TY  - JOUR
AU  - Nišavić, Marija
AU  - Masnikosa, Romana
AU  - Butorac, Ana
AU  - Perica, Kristina
AU  - Rilak, Ana
AU  - Korićanac, Lela
AU  - Hozić, Amela
AU  - Petković, Marijana
AU  - Cindrić, Mario
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1124
AB  - Hyphenated mass spectrometry (MS) techniques have attained an important position in analysis of covalent and non-covalent interactions of metal complexes with peptides and proteins. The aim of the present study was to qualitatively and quantitatively determine ruthenium binding sites on a protein using tandem mass spectrometry and allied techniques, i.e. liquid chromatography (LC) and inductively coupled plasma optical emission spectrometry (ICP-OES). For that purpose, two newly synthesized Ru(II) complexes of a meridional geometry, namely mer-[Ru(4 Cl-tpy)(en)Cl](+) (1) and mer-[Ru(4 Cl-tpy)(dach)Cl](+) (2) (where 4 Cl-tpy = 4-chloro-2,2:6,2 -terpyridine, en = 1,2-diaminoethane and dach = 1,2-diaminocyclohexane), and bovine serum albumin were used. The binding of the complexes to the protein was investigated by means of size exclusion- and reversed phase-LC, ICP OES, matrix-assisted laser desorption ionization MS and MS/MS. Ruthenated peptide sequence and a binding target amino acid were revealed through accurate elucidation of MS/MS spectra. The results obtained in this study suggest a high binding capacity of the protein towards both complexes, with up to 5.77 +/- 0.14 and 6.95 +/- 0.43 mol of 1 and 2 bound per mol of protein, respectively. The proposed binding mechanism for the selected complexes includes the release of Cl ligand, its replacement with water molecule and further coordination to electron donor histidine residue. (C) 2016 Elsevier Inc. All rights reserved.
T2  - Journal of Inorganic Biochemistry
T1  - Elucidation of the binding sites of two novel Ru(II) complexes on bovine serum albumin
VL  - 159
SP  - 89
EP  - 95
DO  - 10.1016/j.jinorgbio.2016.02.034
ER  - 

@article{
author = "Nišavić, Marija and Masnikosa, Romana and Butorac, Ana and Perica, Kristina and Rilak, Ana and Korićanac, Lela and Hozić, Amela and Petković, Marijana and Cindrić, Mario",
year = "2016",
abstract = "Hyphenated mass spectrometry (MS) techniques have attained an important position in analysis of covalent and non-covalent interactions of metal complexes with peptides and proteins. The aim of the present study was to qualitatively and quantitatively determine ruthenium binding sites on a protein using tandem mass spectrometry and allied techniques, i.e. liquid chromatography (LC) and inductively coupled plasma optical emission spectrometry (ICP-OES). For that purpose, two newly synthesized Ru(II) complexes of a meridional geometry, namely mer-[Ru(4 Cl-tpy)(en)Cl](+) (1) and mer-[Ru(4 Cl-tpy)(dach)Cl](+) (2) (where 4 Cl-tpy = 4-chloro-2,2:6,2 -terpyridine, en = 1,2-diaminoethane and dach = 1,2-diaminocyclohexane), and bovine serum albumin were used. The binding of the complexes to the protein was investigated by means of size exclusion- and reversed phase-LC, ICP OES, matrix-assisted laser desorption ionization MS and MS/MS. Ruthenated peptide sequence and a binding target amino acid were revealed through accurate elucidation of MS/MS spectra. The results obtained in this study suggest a high binding capacity of the protein towards both complexes, with up to 5.77 +/- 0.14 and 6.95 +/- 0.43 mol of 1 and 2 bound per mol of protein, respectively. The proposed binding mechanism for the selected complexes includes the release of Cl ligand, its replacement with water molecule and further coordination to electron donor histidine residue. (C) 2016 Elsevier Inc. All rights reserved.",
journal = "Journal of Inorganic Biochemistry",
title = "Elucidation of the binding sites of two novel Ru(II) complexes on bovine serum albumin",
volume = "159",
pages = "89-95",
doi = "10.1016/j.jinorgbio.2016.02.034"
}

Nišavić, M., Masnikosa, R., Butorac, A., Perica, K., Rilak, A., Korićanac, L., Hozić, A., Petković, M.,& Cindrić, M.. (2016). Elucidation of the binding sites of two novel Ru(II) complexes on bovine serum albumin. in Journal of Inorganic Biochemistry, 159, 89-95.
https://doi.org/10.1016/j.jinorgbio.2016.02.034

Nišavić M, Masnikosa R, Butorac A, Perica K, Rilak A, Korićanac L, Hozić A, Petković M, Cindrić M. Elucidation of the binding sites of two novel Ru(II) complexes on bovine serum albumin. in Journal of Inorganic Biochemistry. 2016;159:89-95.
doi:10.1016/j.jinorgbio.2016.02.034 .

Nišavić, Marija, Masnikosa, Romana, Butorac, Ana, Perica, Kristina, Rilak, Ana, Korićanac, Lela, Hozić, Amela, Petković, Marijana, Cindrić, Mario, "Elucidation of the binding sites of two novel Ru(II) complexes on bovine serum albumin" in Journal of Inorganic Biochemistry, 159 (2016):89-95,
https://doi.org/10.1016/j.jinorgbio.2016.02.034 . .