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 . .