Three Re(V) complexes of structural formulas [ReOCl2L(PPh3)], where L is pyridine-2-carboxylic acid (C1), 3-methyl-pyridine-2-carboxylic acid (C2) and 6-methyl-pyridine-2-carboxylic acid (C3) were synthesized andcharacterized using NMR, IR spectroscopy and mass spectrometry. Crystal structures of all three complexes havebeen additionally confirmed by X-ray analysis. The biological activity has been investigated in the panel of tumorcell lines A549, PANC-1, MDA-MB-231, MCF-7, LS-174, EAhy.926 and one in non-tumor cell line MRC-5. OnlyC1 showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cellsMDA-MB-231 with IC50 68.90 ± 1.73 μM and pancreatic adenocarcinoma cells PANC-1 with IC50 69.84 ± 2.3μM. Both cell lines are characterized by a highly invasive and resistant phenotype. Drug combination studies inPANC-1 cells with C1 and Verapamil hydrochloride (VRP), which is the established inhibitor of efflux transporterP-glycoprotein (Pgp), reveal...ed enhancement of antiproliferative action of the complex in a dose-dependentmanner, and slight arrest of cell cycle in the S phase. Also, a depletion of the glutathione (GSH) level by Lbuthionine-sulfoximine (L-BSO) at sub-toxic concentrations (100 μM) caused an increase of activity of C1 to theIC50 57.67 ± 6.51 (μM). A morphological analysis in PANC-1 cells by dual acridine orange/ethidium bromidestaining, revealed apoptotic potential of complex C1 and a slower kinetic of cell death induction, suggesting adifferent mechanism of action compared to cisplatin.
This is the peer-reviewed version of the following article: Petrović, T.; Gligorijević, N.; Belaj, F.; Aranđelović, S.; Mihajlović-Lalić, L. E.; Grgurić-Šipka, S.; Poljarević, J. Drug Combination Study of Novel Oxorhenium(V) Complexes. Journal of Inorganic Biochemistry 2022, 231, 111807. https://doi.org/10.1016/j.jinorgbio.2022.111807.
TY - JOUR
AU - Petrović, Tamara
AU - Gligorijević, Nevenka
AU - Belaj, Ferdinand
AU - Aranđelović, Sandra
AU - Mihajlović-Lalić, Ljiljana E.
AU - Grgurić-Šipka, Sanja
AU - Poljarević, Jelena
PY - 2022
UR - http://cherry.chem.bg.ac.rs/handle/123456789/5047
AB - Three Re(V) complexes of structural formulas [ReOCl2L(PPh3)], where L is pyridine-2-carboxylic acid (C1), 3-methyl-pyridine-2-carboxylic acid (C2) and 6-methyl-pyridine-2-carboxylic acid (C3) were synthesized andcharacterized using NMR, IR spectroscopy and mass spectrometry. Crystal structures of all three complexes havebeen additionally confirmed by X-ray analysis. The biological activity has been investigated in the panel of tumorcell lines A549, PANC-1, MDA-MB-231, MCF-7, LS-174, EAhy.926 and one in non-tumor cell line MRC-5. OnlyC1 showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cellsMDA-MB-231 with IC50 68.90 ± 1.73 μM and pancreatic adenocarcinoma cells PANC-1 with IC50 69.84 ± 2.3μM. Both cell lines are characterized by a highly invasive and resistant phenotype. Drug combination studies inPANC-1 cells with C1 and Verapamil hydrochloride (VRP), which is the established inhibitor of efflux transporterP-glycoprotein (Pgp), revealed enhancement of antiproliferative action of the complex in a dose-dependentmanner, and slight arrest of cell cycle in the S phase. Also, a depletion of the glutathione (GSH) level by Lbuthionine-sulfoximine (L-BSO) at sub-toxic concentrations (100 μM) caused an increase of activity of C1 to theIC50 57.67 ± 6.51 (μM). A morphological analysis in PANC-1 cells by dual acridine orange/ethidium bromidestaining, revealed apoptotic potential of complex C1 and a slower kinetic of cell death induction, suggesting adifferent mechanism of action compared to cisplatin.
PB - Elsevier
T2 - Journal of Inorganic Biochemistry
T1 - Drug combination study of novel oxorhenium(V) complexes
VL - 231
SP - 111807
DO - 10.1016/j.jinorgbio.2022.111807
ER -
@article{
author = "Petrović, Tamara and Gligorijević, Nevenka and Belaj, Ferdinand and Aranđelović, Sandra and Mihajlović-Lalić, Ljiljana E. and Grgurić-Šipka, Sanja and Poljarević, Jelena",
year = "2022",
abstract = "Three Re(V) complexes of structural formulas [ReOCl2L(PPh3)], where L is pyridine-2-carboxylic acid (C1), 3-methyl-pyridine-2-carboxylic acid (C2) and 6-methyl-pyridine-2-carboxylic acid (C3) were synthesized andcharacterized using NMR, IR spectroscopy and mass spectrometry. Crystal structures of all three complexes havebeen additionally confirmed by X-ray analysis. The biological activity has been investigated in the panel of tumorcell lines A549, PANC-1, MDA-MB-231, MCF-7, LS-174, EAhy.926 and one in non-tumor cell line MRC-5. OnlyC1 showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cellsMDA-MB-231 with IC50 68.90 ± 1.73 μM and pancreatic adenocarcinoma cells PANC-1 with IC50 69.84 ± 2.3μM. Both cell lines are characterized by a highly invasive and resistant phenotype. Drug combination studies inPANC-1 cells with C1 and Verapamil hydrochloride (VRP), which is the established inhibitor of efflux transporterP-glycoprotein (Pgp), revealed enhancement of antiproliferative action of the complex in a dose-dependentmanner, and slight arrest of cell cycle in the S phase. Also, a depletion of the glutathione (GSH) level by Lbuthionine-sulfoximine (L-BSO) at sub-toxic concentrations (100 μM) caused an increase of activity of C1 to theIC50 57.67 ± 6.51 (μM). A morphological analysis in PANC-1 cells by dual acridine orange/ethidium bromidestaining, revealed apoptotic potential of complex C1 and a slower kinetic of cell death induction, suggesting adifferent mechanism of action compared to cisplatin.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "Drug combination study of novel oxorhenium(V) complexes",
volume = "231",
pages = "111807",
doi = "10.1016/j.jinorgbio.2022.111807"
}
Petrović, T., Gligorijević, N., Belaj, F., Aranđelović, S., Mihajlović-Lalić, L. E., Grgurić-Šipka, S.,& Poljarević, J.. (2022). Drug combination study of novel oxorhenium(V) complexes. in Journal of Inorganic Biochemistry
Elsevier., 231, 111807.
https://doi.org/10.1016/j.jinorgbio.2022.111807
Petrović T, Gligorijević N, Belaj F, Aranđelović S, Mihajlović-Lalić LE, Grgurić-Šipka S, Poljarević J. Drug combination study of novel oxorhenium(V) complexes. in Journal of Inorganic Biochemistry. 2022;231:111807.
doi:10.1016/j.jinorgbio.2022.111807 .
Petrović, Tamara, Gligorijević, Nevenka, Belaj, Ferdinand, Aranđelović, Sandra, Mihajlović-Lalić, Ljiljana E., Grgurić-Šipka, Sanja, Poljarević, Jelena, "Drug combination study of novel oxorhenium(V) complexes" in Journal of Inorganic Biochemistry, 231 (2022):111807,
https://doi.org/10.1016/j.jinorgbio.2022.111807 . .
