Antitumor activity of organoruthenium complexes with chelate aromatic ligands, derived from 1,10-phenantroline: Synthesis and biological activity
Samo za registrovane korisnike
2020
Autori
Savić, Aleksandar
Gligorijević, Nevenka

Aranđelović, Sandra
Dojčinović, Biljana

Kaczmarek, Anna M.
Radulović, Siniša

Van Deun, Rik
Van Hecke, Kristof
Članak u časopisu (Objavljena verzija)

Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Ključne reči:
3D cell culture / Crystal structure / Cytotoxicity / Organoruthenium complexesIzvor:
Journal of Inorganic Biochemistry, 2020, 202, 110869-Izdavač:
- Elsevier
Finansiranje / projekti:
- Erasmus Mundus Basileus V project
- Hercules Foundation (project AUGE/11/029 “3D-SPACE: 3D Structural Platform Aiming for Chemical Excellence”)
- Special Research Fund (BOF) – UGent (project 01N03217)
- Racionalni dizajn i sinteza biološki aktivnih i koordinacionih jedinjenja i funkcionalnih materijala, relevantnih u (bio)nanotehnologiji (RS-172035)
- Farmakodinamska i farmakogenomska ispitivanja novijih lekova u lečenju solidnih tumora (RS-41026)
DOI: 10.1016/j.jinorgbio.2019.110869
ISSN: 0162-0134
WoS: 000502686300007
Scopus: 2-s2.0-85073921098
Institucija/grupa
IHTMTY - JOUR AU - Savić, Aleksandar AU - Gligorijević, Nevenka AU - Aranđelović, Sandra AU - Dojčinović, Biljana AU - Kaczmarek, Anna M. AU - Radulović, Siniša AU - Van Deun, Rik AU - Van Hecke, Kristof PY - 2020 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/3352 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 SP - 110869 DO - 10.1016/j.jinorgbio.2019.110869 ER -
@article{ author = "Savić, Aleksandar and Gligorijević, Nevenka and Aranđelović, Sandra and Dojčinović, Biljana 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 = "110869-110869", doi = "10.1016/j.jinorgbio.2019.110869" }
Savić, A., Gligorijević, N., Aranđelović, S., Dojčinović, B., 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 B, 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, 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 . .