Tumor Selective Ru(III) Schiff Bases Complexes with Strong In Vitro Activity Toward Cisplatin-Resistant MDA-MB-231 Breast Cancer Cells
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2023
Authors
Pavlović, Marijana
Kahrović, Emira
Aranđelović, Sandra

Radulović, Siniša
Ilich, Predrag-Peter
Grgurić-Šipka, Sanja

Ljubijankić, Nevzeta
Žilić, Dijana
Jurec, Jurica
Article (Published version)

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Show full item recordAbstract
Novel ruthenium(III) complexes of general formula Na[
RuCl2(L1−3-N,O)2] where L(
1–3) denote deprotonated Schiff bases
(
HL1-HL3) derived from 5-substituted salicyladehyde and alkylamine (propyl- or butylamine) were prepared and characterized
based on elemental analysis, mass spectra, infrared, electron spin/paramagnetic resonance (ESR/EPR) spectroscopy,
and cyclovoltammetric study. Optimization of five isomers of complex C1 was done by DFT calculation. The interaction
of C1–C3 complexes with DNA (Deoxyribonucleic acid) and BSA (Bovine serum albumin) was investigated by electron
spectroscopy and fluorescence quenching. The cytotoxic activity of C1–C3 was investigated in a panel of four human cancer
cell lines (K562, A549, EA.hy926, MDA-MB-231) and one human non-tumor cell line (MRC-5). Complexes displayed an
apparent cytoselective profile, with IC50
values in the low micromolar range from 1.6 ± 0.3 to 23.0 ± 0.1 μM. Cisplatinresistant
triple-negative breast cancer cells MDA...-MB-231 displayed the highest sensitivity to complexes, with Ru(III)
compound containing two chlorides and two deprotonated N-propyl-5-chloro-salicylidenimine (hereinafter C1) as the most
potent (
IC50 = 1.6 μM), and approximately ten times more active than cisplatin (
IC50 = 21.9 μM). MDA-MB-231 cells treated
for 24 h with C1 presented with apoptotic morphology, as seen by acridine orange/ethidium bromide staining, while 48 h of
treatment induced DNA fragmentation, and necrotic changes in cells, as seen by flow cytometry analysis. Drug-accumulation
study by inductively coupled plasma mass spectrometry (ICP-MS) demonstrated markedly higher intracellular accumulation
of C1 compared with cisplatin.
Keywords:
Schiff bases, Cytoselectivity, Breast cancer, Apoptosis / Schiff bases / Cytoselectivity / Breast cancerSource:
J. Biol. Inorg. Chem., 2023, 28, 263-284Publisher:
- Springer
Funding / projects:
- Federal Ministry of Education and Science of Bosnia and Herzegovina (Grant no. 05-39-2619-1/18)
- Pharmacodynamic and pharmacogenomic research of new drugs in the treatment of solid tumors (RS-41026)
- Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200043 (Institute of Oncology and Radiology of Serbia, Belgrade) (RS-200043)
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Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Pavlović, Marijana AU - Kahrović, Emira AU - Aranđelović, Sandra AU - Radulović, Siniša AU - Ilich, Predrag-Peter AU - Grgurić-Šipka, Sanja AU - Ljubijankić, Nevzeta AU - Žilić, Dijana AU - Jurec, Jurica PY - 2023 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5901 AB - Novel ruthenium(III) complexes of general formula Na[ RuCl2(L1−3-N,O)2] where L( 1–3) denote deprotonated Schiff bases ( HL1-HL3) derived from 5-substituted salicyladehyde and alkylamine (propyl- or butylamine) were prepared and characterized based on elemental analysis, mass spectra, infrared, electron spin/paramagnetic resonance (ESR/EPR) spectroscopy, and cyclovoltammetric study. Optimization of five isomers of complex C1 was done by DFT calculation. The interaction of C1–C3 complexes with DNA (Deoxyribonucleic acid) and BSA (Bovine serum albumin) was investigated by electron spectroscopy and fluorescence quenching. The cytotoxic activity of C1–C3 was investigated in a panel of four human cancer cell lines (K562, A549, EA.hy926, MDA-MB-231) and one human non-tumor cell line (MRC-5). Complexes displayed an apparent cytoselective profile, with IC50 values in the low micromolar range from 1.6 ± 0.3 to 23.0 ± 0.1 μM. Cisplatinresistant triple-negative breast cancer cells MDA-MB-231 displayed the highest sensitivity to complexes, with Ru(III) compound containing two chlorides and two deprotonated N-propyl-5-chloro-salicylidenimine (hereinafter C1) as the most potent ( IC50 = 1.6 μM), and approximately ten times more active than cisplatin ( IC50 = 21.9 μM). MDA-MB-231 cells treated for 24 h with C1 presented with apoptotic morphology, as seen by acridine orange/ethidium bromide staining, while 48 h of treatment induced DNA fragmentation, and necrotic changes in cells, as seen by flow cytometry analysis. Drug-accumulation study by inductively coupled plasma mass spectrometry (ICP-MS) demonstrated markedly higher intracellular accumulation of C1 compared with cisplatin. PB - Springer T2 - J. Biol. Inorg. Chem. T1 - Tumor Selective Ru(III) Schiff Bases Complexes with Strong In Vitro Activity Toward Cisplatin-Resistant MDA-MB-231 Breast Cancer Cells VL - 28 SP - 263 EP - 284 DO - 10.1007/s00775-023-01989-0 ER -
@article{ author = "Pavlović, Marijana and Kahrović, Emira and Aranđelović, Sandra and Radulović, Siniša and Ilich, Predrag-Peter and Grgurić-Šipka, Sanja and Ljubijankić, Nevzeta and Žilić, Dijana and Jurec, Jurica", year = "2023", abstract = "Novel ruthenium(III) complexes of general formula Na[ RuCl2(L1−3-N,O)2] where L( 1–3) denote deprotonated Schiff bases ( HL1-HL3) derived from 5-substituted salicyladehyde and alkylamine (propyl- or butylamine) were prepared and characterized based on elemental analysis, mass spectra, infrared, electron spin/paramagnetic resonance (ESR/EPR) spectroscopy, and cyclovoltammetric study. Optimization of five isomers of complex C1 was done by DFT calculation. The interaction of C1–C3 complexes with DNA (Deoxyribonucleic acid) and BSA (Bovine serum albumin) was investigated by electron spectroscopy and fluorescence quenching. The cytotoxic activity of C1–C3 was investigated in a panel of four human cancer cell lines (K562, A549, EA.hy926, MDA-MB-231) and one human non-tumor cell line (MRC-5). Complexes displayed an apparent cytoselective profile, with IC50 values in the low micromolar range from 1.6 ± 0.3 to 23.0 ± 0.1 μM. Cisplatinresistant triple-negative breast cancer cells MDA-MB-231 displayed the highest sensitivity to complexes, with Ru(III) compound containing two chlorides and two deprotonated N-propyl-5-chloro-salicylidenimine (hereinafter C1) as the most potent ( IC50 = 1.6 μM), and approximately ten times more active than cisplatin ( IC50 = 21.9 μM). MDA-MB-231 cells treated for 24 h with C1 presented with apoptotic morphology, as seen by acridine orange/ethidium bromide staining, while 48 h of treatment induced DNA fragmentation, and necrotic changes in cells, as seen by flow cytometry analysis. Drug-accumulation study by inductively coupled plasma mass spectrometry (ICP-MS) demonstrated markedly higher intracellular accumulation of C1 compared with cisplatin.", publisher = "Springer", journal = "J. Biol. Inorg. Chem.", title = "Tumor Selective Ru(III) Schiff Bases Complexes with Strong In Vitro Activity Toward Cisplatin-Resistant MDA-MB-231 Breast Cancer Cells", volume = "28", pages = "263-284", doi = "10.1007/s00775-023-01989-0" }
Pavlović, M., Kahrović, E., Aranđelović, S., Radulović, S., Ilich, P., Grgurić-Šipka, S., Ljubijankić, N., Žilić, D.,& Jurec, J.. (2023). Tumor Selective Ru(III) Schiff Bases Complexes with Strong In Vitro Activity Toward Cisplatin-Resistant MDA-MB-231 Breast Cancer Cells. in J. Biol. Inorg. Chem. Springer., 28, 263-284. https://doi.org/10.1007/s00775-023-01989-0
Pavlović M, Kahrović E, Aranđelović S, Radulović S, Ilich P, Grgurić-Šipka S, Ljubijankić N, Žilić D, Jurec J. Tumor Selective Ru(III) Schiff Bases Complexes with Strong In Vitro Activity Toward Cisplatin-Resistant MDA-MB-231 Breast Cancer Cells. in J. Biol. Inorg. Chem.. 2023;28:263-284. doi:10.1007/s00775-023-01989-0 .
Pavlović, Marijana, Kahrović, Emira, Aranđelović, Sandra, Radulović, Siniša, Ilich, Predrag-Peter, Grgurić-Šipka, Sanja, Ljubijankić, Nevzeta, Žilić, Dijana, Jurec, Jurica, "Tumor Selective Ru(III) Schiff Bases Complexes with Strong In Vitro Activity Toward Cisplatin-Resistant MDA-MB-231 Breast Cancer Cells" in J. Biol. Inorg. Chem., 28 (2023):263-284, https://doi.org/10.1007/s00775-023-01989-0 . .