TY  - JOUR
AU  - Savić, Aleksandar
AU  - Gligorijević, Nevenka
AU  - Aranđelović, Sandra
AU  - Dojčinović, Biljana P.
AU  - Kaczmarek, Anna M.
AU  - Radulović, Siniša
AU  - Van Deun, Rik
AU  - Van Hecke, Kristof
PY  - 2020
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3781
AB  - The monocationic chloro complexes containing chelating N∩N ligands: [(η6-p-cymene)Ru(L1–4)Cl]+ (1–4), where L1 = 4-methyl-1,10-phenantroline, L2 = dipyrido[3,2-a:2′,3′-c]phenazine, L3 = 11-chloro-dipyrido[3,2-a:2′,3′-c]phenazine, L4 = 11-nitro-dipyrido[3,2-a:2′,3′-c]phenazine; p-cymene = 1-methyl-4-isopropylbenzene) have been prepared and characterized as the hexafluorophosphate salts. The biological activity of 1–4 has been investigated in selected 2D monolayer cell cultures (A549, PANC-1, MDA-MB-231, MRC-5). All investigated ruthenium complexes showed similar or even better cytotoxicity to cisplatin. However, there was no significant reduction in growth of PANC-1 cells in a 3D cell culture of multicellular tumor spheroids (MCTS) after treatment with 2–4, while the cisplatin treatment induced retardation in MCTS growth. Flow cytometry analysis of the cell cycle of PANC-1 cells shows that 3 caused changes of cell cycle phase distribution characterized by slight accumulation of cells in the G2-M phase. Absence of the Sub-G1 phase in the cell cycle of the treated cells indicated that there was no fragmentation of DNA for the analyzed time intervals (48 and 72 h treatment). Fluorescent microscopy, after acridine orange/ethidium bromide staining, revealed that the investigated ruthenium complexes induced some characteristics of apoptotic morphology (shrinking and condensation of chromatin) with notably preserved integrity of the plasma membrane. Investigation of cellular uptake and DNA - fraction accumulation performed by inductively coupled plasma mass spectrometry in PANC-1 cells with equimolar concentrations (5 μM) of 2–4 and cisplatin showed more efficient cellular uptake and DNA - fraction accumulation of complex 3 compared to complexes 2 and 4.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - Antitumor activity of organoruthenium complexes with chelate aromatic ligands, derived from 1,10-phenantroline: Synthesis and biological activity
VL  - 202
SP  - 110869
DO  - 10.1016/j.jinorgbio.2019.110869
ER  - 

@article{
author = "Savić, Aleksandar and Gligorijević, Nevenka and Aranđelović, Sandra and Dojčinović, Biljana P. and Kaczmarek, Anna M. and Radulović, Siniša and Van Deun, Rik and Van Hecke, Kristof",
year = "2020",
abstract = "The monocationic chloro complexes containing chelating N∩N ligands: [(η6-p-cymene)Ru(L1–4)Cl]+ (1–4), where L1 = 4-methyl-1,10-phenantroline, L2 = dipyrido[3,2-a:2′,3′-c]phenazine, L3 = 11-chloro-dipyrido[3,2-a:2′,3′-c]phenazine, L4 = 11-nitro-dipyrido[3,2-a:2′,3′-c]phenazine; p-cymene = 1-methyl-4-isopropylbenzene) have been prepared and characterized as the hexafluorophosphate salts. The biological activity of 1–4 has been investigated in selected 2D monolayer cell cultures (A549, PANC-1, MDA-MB-231, MRC-5). All investigated ruthenium complexes showed similar or even better cytotoxicity to cisplatin. However, there was no significant reduction in growth of PANC-1 cells in a 3D cell culture of multicellular tumor spheroids (MCTS) after treatment with 2–4, while the cisplatin treatment induced retardation in MCTS growth. Flow cytometry analysis of the cell cycle of PANC-1 cells shows that 3 caused changes of cell cycle phase distribution characterized by slight accumulation of cells in the G2-M phase. Absence of the Sub-G1 phase in the cell cycle of the treated cells indicated that there was no fragmentation of DNA for the analyzed time intervals (48 and 72 h treatment). Fluorescent microscopy, after acridine orange/ethidium bromide staining, revealed that the investigated ruthenium complexes induced some characteristics of apoptotic morphology (shrinking and condensation of chromatin) with notably preserved integrity of the plasma membrane. Investigation of cellular uptake and DNA - fraction accumulation performed by inductively coupled plasma mass spectrometry in PANC-1 cells with equimolar concentrations (5 μM) of 2–4 and cisplatin showed more efficient cellular uptake and DNA - fraction accumulation of complex 3 compared to complexes 2 and 4.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "Antitumor activity of organoruthenium complexes with chelate aromatic ligands, derived from 1,10-phenantroline: Synthesis and biological activity",
volume = "202",
pages = "110869",
doi = "10.1016/j.jinorgbio.2019.110869"
}

Savić, A., Gligorijević, N., Aranđelović, S., Dojčinović, B. P., Kaczmarek, A. M., Radulović, S., Van Deun, R.,& Van Hecke, K.. (2020). Antitumor activity of organoruthenium complexes with chelate aromatic ligands, derived from 1,10-phenantroline: Synthesis and biological activity. in Journal of Inorganic Biochemistry
Elsevier., 202, 110869.
https://doi.org/10.1016/j.jinorgbio.2019.110869

Savić A, Gligorijević N, Aranđelović S, Dojčinović BP, Kaczmarek AM, Radulović S, Van Deun R, Van Hecke K. Antitumor activity of organoruthenium complexes with chelate aromatic ligands, derived from 1,10-phenantroline: Synthesis and biological activity. in Journal of Inorganic Biochemistry. 2020;202:110869.
doi:10.1016/j.jinorgbio.2019.110869 .

Savić, Aleksandar, Gligorijević, Nevenka, Aranđelović, Sandra, Dojčinović, Biljana P., Kaczmarek, Anna M., Radulović, Siniša, Van Deun, Rik, Van Hecke, Kristof, "Antitumor activity of organoruthenium complexes with chelate aromatic ligands, derived from 1,10-phenantroline: Synthesis and biological activity" in Journal of Inorganic Biochemistry, 202 (2020):110869,
https://doi.org/10.1016/j.jinorgbio.2019.110869 . .