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
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AuthorsMilutinović, Milan M.
Čanović, Petar P.
Stevanović, Dragana D.
Zarić, Milan M.
Jakovljević, Vladimir Lj.
Trajković, Vladimir S.
Rilak Simović, Ana
Article (Published version)
© 2018 American Chemical Society
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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.
Source:Organometallics, 2018, 37, 22, 4250-4266
- Mechanistic studies of the reactions of transition metal ion complexes with biologically relevant molecules (RS-172011)
- Molecular determinants of innate immunity in autoimmunity and tumorogenesis (RS-175069)
- Developing infrastructure for priority research fields (RS-175103)
- Novel Electrochemical and Chemical Methods in Synthesis of Organic Compounds of Interest for Medicine and Material Chemistry (RS-172034)
- Faculty of Medical Sciences, University of Kragujevac [MP 01/18]
ISSN: 0276-7333 (print); 1520-6041 (electrical)