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
Само за регистроване кориснике
2018
Аутори
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
Чланак у часопису (Објављена верзија)
,
© 2018 American Chemical Society
Метаподаци
Приказ свих података о документуАпстракт
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 an...d 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.
Извор:
Organometallics, 2018, 37, 22, 4250-4266Финансирање / пројекти:
- Испитивање механизма реакција комплекса јона прелазних метала са биолошки значајним молекулима (RS-MESTD-Basic Research (BR or ON)-172011)
- Молекулске детерминанте урођене имуности у аутоимунским болестима и канцерогенези (RS-MESTD-Basic Research (BR or ON)-175069)
- Развој инфраструктуре за приоритетна поља науке (RS-MESTD-Basic Research (BR or ON)-175103)
- Нове електрохемијске и хемијске методе у синтези органских једињења од интереса за медицину и хемију материјала (RS-MESTD-Basic Research (BR or ON)-172034)
- Faculty of Medical Sciences, University of Kragujevac [MP 01/18]
DOI: 10.1021/acs.organomet.8b00604
ISSN: 0276-7333; 1520-6041
WoS: 000451650200011
Scopus: 2-s2.0-85056723541
URI
http://pubs.acs.org/doi/10.1021/acs.organomet.8b00604https://vinar.vin.bg.ac.rs/handle/123456789/7967
Колекције
Институција/група
VinčaTY - 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 . .