TY  - JOUR
AU  - Jovanovic, Katarina K.
AU  - Tanic, Miljana
AU  - Ivanovic, Ivanka
AU  - Gligorijević, Nevenka
AU  - Dojčinović, Biljana
AU  - Radulovic, Sinisa
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4386
AB  - Ruthenium(II)-arene complexes are promising drug candidates for the therapy of solid tumors. In previous work, seven new compounds of the general formula [Ru(eta(6)-p-cymene)(L1-7)Cl] were synthesized and characterized, of which the complex with L = isoquinoline-3-carboxylic acid (RuT7) was two times as active on HeLa cells compared to normal cell line MRC-5, as indicated by ICso values determined after 48 h of incubation (45.4 +/- 3.0 vs. 842 +/- 5.7 mu M, respectively). In the present study, cell cycle analysis of HeLa cells treated with RuT7 showed S phase arrest and an increase in sub-G1 population. The apoptotic potential of the title compound was confirmed with the Annexin V-FITC/PI assay together with a morphological evaluation of cells using fluorescent microscopy. Analysis of the intracellular accumulation of ruthenium showed 8.9 ng Ru/10(6) cells after 6 h of incubation. To gain further insight in the molecular mechanism of action of RuT7 on HeLa cells, a whole-transcriptome microarray gene expression analysis was performed. Analysis of functional categories and signaling and biochemical pathways associated with the response of HeLa cells to treatment with RuT7 showed that it leads the cells through the intrinsic (mitochondrial) apoptotic pathway, via indirect DNA damage due to the action of reactive oxygen species, and through direct DNA binding of RuT7. Statistical analysis for enrichment of gene sets associated with known drug-induced toxicities identified fewer associated toxicity profiles in RuT7-treated cells compared to cisplatin treatment. Altogether these results provide the basis for further development of RuT7 in animal and pre-clinical studies as a potential drug candidate.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand
VL  - 163
SP  - 362
EP  - 373
DO  - 10.1016/j.jinorgbio.2016.04.011
ER  - 

@article{
author = "Jovanovic, Katarina K. and Tanic, Miljana and Ivanovic, Ivanka and Gligorijević, Nevenka and Dojčinović, Biljana and Radulovic, Sinisa",
year = "2016",
abstract = "Ruthenium(II)-arene complexes are promising drug candidates for the therapy of solid tumors. In previous work, seven new compounds of the general formula [Ru(eta(6)-p-cymene)(L1-7)Cl] were synthesized and characterized, of which the complex with L = isoquinoline-3-carboxylic acid (RuT7) was two times as active on HeLa cells compared to normal cell line MRC-5, as indicated by ICso values determined after 48 h of incubation (45.4 +/- 3.0 vs. 842 +/- 5.7 mu M, respectively). In the present study, cell cycle analysis of HeLa cells treated with RuT7 showed S phase arrest and an increase in sub-G1 population. The apoptotic potential of the title compound was confirmed with the Annexin V-FITC/PI assay together with a morphological evaluation of cells using fluorescent microscopy. Analysis of the intracellular accumulation of ruthenium showed 8.9 ng Ru/10(6) cells after 6 h of incubation. To gain further insight in the molecular mechanism of action of RuT7 on HeLa cells, a whole-transcriptome microarray gene expression analysis was performed. Analysis of functional categories and signaling and biochemical pathways associated with the response of HeLa cells to treatment with RuT7 showed that it leads the cells through the intrinsic (mitochondrial) apoptotic pathway, via indirect DNA damage due to the action of reactive oxygen species, and through direct DNA binding of RuT7. Statistical analysis for enrichment of gene sets associated with known drug-induced toxicities identified fewer associated toxicity profiles in RuT7-treated cells compared to cisplatin treatment. Altogether these results provide the basis for further development of RuT7 in animal and pre-clinical studies as a potential drug candidate.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand",
volume = "163",
pages = "362-373",
doi = "10.1016/j.jinorgbio.2016.04.011"
}

Jovanovic, K. K., Tanic, M., Ivanovic, I., Gligorijević, N., Dojčinović, B.,& Radulovic, S.. (2016). Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand. in Journal of Inorganic Biochemistry
Elsevier., 163, 362-373.
https://doi.org/10.1016/j.jinorgbio.2016.04.011

Jovanovic KK, Tanic M, Ivanovic I, Gligorijević N, Dojčinović B, Radulovic S. Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand. in Journal of Inorganic Biochemistry. 2016;163:362-373.
doi:10.1016/j.jinorgbio.2016.04.011 .

Jovanovic, Katarina K., Tanic, Miljana, Ivanovic, Ivanka, Gligorijević, Nevenka, Dojčinović, Biljana, Radulovic, Sinisa, "Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand" in Journal of Inorganic Biochemistry, 163 (2016):362-373,
https://doi.org/10.1016/j.jinorgbio.2016.04.011 . .

TY  - JOUR
AU  - Jovanovic, Katarina K.
AU  - Tanic, Miljana
AU  - Ivanovic, Ivanka
AU  - Gligorijević, Nevenka
AU  - Dojčinović, Biljana
AU  - Radulovic, Sinisa
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1984
AB  - Ruthenium(II)-arene complexes are promising drug candidates for the therapy of solid tumors. In previous work, seven new compounds of the general formula [Ru(eta(6)-p-cymene)(L1-7)Cl] were synthesized and characterized, of which the complex with L = isoquinoline-3-carboxylic acid (RuT7) was two times as active on HeLa cells compared to normal cell line MRC-5, as indicated by ICso values determined after 48 h of incubation (45.4 +/- 3.0 vs. 842 +/- 5.7 mu M, respectively). In the present study, cell cycle analysis of HeLa cells treated with RuT7 showed S phase arrest and an increase in sub-G1 population. The apoptotic potential of the title compound was confirmed with the Annexin V-FITC/PI assay together with a morphological evaluation of cells using fluorescent microscopy. Analysis of the intracellular accumulation of ruthenium showed 8.9 ng Ru/10(6) cells after 6 h of incubation. To gain further insight in the molecular mechanism of action of RuT7 on HeLa cells, a whole-transcriptome microarray gene expression analysis was performed. Analysis of functional categories and signaling and biochemical pathways associated with the response of HeLa cells to treatment with RuT7 showed that it leads the cells through the intrinsic (mitochondrial) apoptotic pathway, via indirect DNA damage due to the action of reactive oxygen species, and through direct DNA binding of RuT7. Statistical analysis for enrichment of gene sets associated with known drug-induced toxicities identified fewer associated toxicity profiles in RuT7-treated cells compared to cisplatin treatment. Altogether these results provide the basis for further development of RuT7 in animal and pre-clinical studies as a potential drug candidate.
PB  - Elsevier Science Inc, New York
T2  - Journal of Inorganic Biochemistry
T1  - Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand
VL  - 163
SP  - 362
EP  - 373
DO  - 10.1016/j.jinorgbio.2016.04.011
ER  - 

@article{
author = "Jovanovic, Katarina K. and Tanic, Miljana and Ivanovic, Ivanka and Gligorijević, Nevenka and Dojčinović, Biljana and Radulovic, Sinisa",
year = "2016",
abstract = "Ruthenium(II)-arene complexes are promising drug candidates for the therapy of solid tumors. In previous work, seven new compounds of the general formula [Ru(eta(6)-p-cymene)(L1-7)Cl] were synthesized and characterized, of which the complex with L = isoquinoline-3-carboxylic acid (RuT7) was two times as active on HeLa cells compared to normal cell line MRC-5, as indicated by ICso values determined after 48 h of incubation (45.4 +/- 3.0 vs. 842 +/- 5.7 mu M, respectively). In the present study, cell cycle analysis of HeLa cells treated with RuT7 showed S phase arrest and an increase in sub-G1 population. The apoptotic potential of the title compound was confirmed with the Annexin V-FITC/PI assay together with a morphological evaluation of cells using fluorescent microscopy. Analysis of the intracellular accumulation of ruthenium showed 8.9 ng Ru/10(6) cells after 6 h of incubation. To gain further insight in the molecular mechanism of action of RuT7 on HeLa cells, a whole-transcriptome microarray gene expression analysis was performed. Analysis of functional categories and signaling and biochemical pathways associated with the response of HeLa cells to treatment with RuT7 showed that it leads the cells through the intrinsic (mitochondrial) apoptotic pathway, via indirect DNA damage due to the action of reactive oxygen species, and through direct DNA binding of RuT7. Statistical analysis for enrichment of gene sets associated with known drug-induced toxicities identified fewer associated toxicity profiles in RuT7-treated cells compared to cisplatin treatment. Altogether these results provide the basis for further development of RuT7 in animal and pre-clinical studies as a potential drug candidate.",
publisher = "Elsevier Science Inc, New York",
journal = "Journal of Inorganic Biochemistry",
title = "Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand",
volume = "163",
pages = "362-373",
doi = "10.1016/j.jinorgbio.2016.04.011"
}

Jovanovic, K. K., Tanic, M., Ivanovic, I., Gligorijević, N., Dojčinović, B.,& Radulovic, S.. (2016). Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand. in Journal of Inorganic Biochemistry
Elsevier Science Inc, New York., 163, 362-373.
https://doi.org/10.1016/j.jinorgbio.2016.04.011

Jovanovic KK, Tanic M, Ivanovic I, Gligorijević N, Dojčinović B, Radulovic S. Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand. in Journal of Inorganic Biochemistry. 2016;163:362-373.
doi:10.1016/j.jinorgbio.2016.04.011 .

Jovanovic, Katarina K., Tanic, Miljana, Ivanovic, Ivanka, Gligorijević, Nevenka, Dojčinović, Biljana, Radulovic, Sinisa, "Cell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid ligand" in Journal of Inorganic Biochemistry, 163 (2016):362-373,
https://doi.org/10.1016/j.jinorgbio.2016.04.011 . .

TY  - JOUR
AU  - Grgurić-Šipka, Sanja
AU  - Ivanovic, Ivanka
AU  - Rakic, Gordana
AU  - Todorović, Nina
AU  - Gligorijević, Nevenka
AU  - Radulovic, Sinisa
AU  - Arion, Vladimir B.
AU  - Keppler, Bernhard K.
AU  - Tešić, Živoslav
PY  - 2010
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/646
AB  - Ruthenium(II)-arene complexes of general formulae [(eta(6)-p-cymene)Ru(L1-3)Cl-2], where L1-3 is 3-acetylpyridine (1), 4-acetylpyridine (2) and 2-amino-5-chloropyridine (3), Correspondingly, [(eta(6)-p-cymene)Ru(HL4,5)Cl-2], where HL4 and HL5 are respectively isonicotinic acid (4) and nicotinic acid (5) and [(eta(6)-p-cymene)Ru(HL6-9)Cl], where H2L6-9 represent 2,3-pyridinedicarboxylic acid (6), 2,4-pyidinedicarboxylic acid (7), 2,5-pyridinedicarboxylic acid (8) and 2,6-pyridinedicarboxylic acid (9), were prepared by the reaction of (eta(6)-p-cymene)(2)RuCl2](2) (10) with the corresponding ligand in 1:2 molar ratio in isopropanol. The complexes were characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopies. According to these data the molecules adopt the usual "three-leg piano-stool" geometry which is common for this type of complexes. The structures of I and 7 were determined by X-ray crystallography. The complexes revealed low antiproliferative activity in six investigated tumor cell lines (HeLa, B16, FemX, MDA-MB-361, MDA-MB-453 and LS-174). The reaction of 6 with 9-methyladenine was studied by H-1 NMR, H-1, H-1 COSY and H-1, H-1 NOESY spectroscopy.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
T2  - European Journal of Medicinal Chemistry
T1  - Ruthenium(II)-arene complexes with functionalized pyridines: Synthesis, characterization and cytotoxic activity
VL  - 45
IS  - 3
SP  - 1051
EP  - 1058
DO  - 10.1016/j.ejmech.2009.11.055
ER  - 

@article{
author = "Grgurić-Šipka, Sanja and Ivanovic, Ivanka and Rakic, Gordana and Todorović, Nina and Gligorijević, Nevenka and Radulovic, Sinisa and Arion, Vladimir B. and Keppler, Bernhard K. and Tešić, Živoslav",
year = "2010",
abstract = "Ruthenium(II)-arene complexes of general formulae [(eta(6)-p-cymene)Ru(L1-3)Cl-2], where L1-3 is 3-acetylpyridine (1), 4-acetylpyridine (2) and 2-amino-5-chloropyridine (3), Correspondingly, [(eta(6)-p-cymene)Ru(HL4,5)Cl-2], where HL4 and HL5 are respectively isonicotinic acid (4) and nicotinic acid (5) and [(eta(6)-p-cymene)Ru(HL6-9)Cl], where H2L6-9 represent 2,3-pyridinedicarboxylic acid (6), 2,4-pyidinedicarboxylic acid (7), 2,5-pyridinedicarboxylic acid (8) and 2,6-pyridinedicarboxylic acid (9), were prepared by the reaction of (eta(6)-p-cymene)(2)RuCl2](2) (10) with the corresponding ligand in 1:2 molar ratio in isopropanol. The complexes were characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopies. According to these data the molecules adopt the usual "three-leg piano-stool" geometry which is common for this type of complexes. The structures of I and 7 were determined by X-ray crystallography. The complexes revealed low antiproliferative activity in six investigated tumor cell lines (HeLa, B16, FemX, MDA-MB-361, MDA-MB-453 and LS-174). The reaction of 6 with 9-methyladenine was studied by H-1 NMR, H-1, H-1 COSY and H-1, H-1 NOESY spectroscopy.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux",
journal = "European Journal of Medicinal Chemistry",
title = "Ruthenium(II)-arene complexes with functionalized pyridines: Synthesis, characterization and cytotoxic activity",
volume = "45",
number = "3",
pages = "1051-1058",
doi = "10.1016/j.ejmech.2009.11.055"
}

Grgurić-Šipka, S., Ivanovic, I., Rakic, G., Todorović, N., Gligorijević, N., Radulovic, S., Arion, V. B., Keppler, B. K.,& Tešić, Ž.. (2010). Ruthenium(II)-arene complexes with functionalized pyridines: Synthesis, characterization and cytotoxic activity. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux., 45(3), 1051-1058.
https://doi.org/10.1016/j.ejmech.2009.11.055

Grgurić-Šipka S, Ivanovic I, Rakic G, Todorović N, Gligorijević N, Radulovic S, Arion VB, Keppler BK, Tešić Ž. Ruthenium(II)-arene complexes with functionalized pyridines: Synthesis, characterization and cytotoxic activity. in European Journal of Medicinal Chemistry. 2010;45(3):1051-1058.
doi:10.1016/j.ejmech.2009.11.055 .

Grgurić-Šipka, Sanja, Ivanovic, Ivanka, Rakic, Gordana, Todorović, Nina, Gligorijević, Nevenka, Radulovic, Sinisa, Arion, Vladimir B., Keppler, Bernhard K., Tešić, Živoslav, "Ruthenium(II)-arene complexes with functionalized pyridines: Synthesis, characterization and cytotoxic activity" in European Journal of Medicinal Chemistry, 45, no. 3 (2010):1051-1058,
https://doi.org/10.1016/j.ejmech.2009.11.055 . .