TY  - CONF
AU  - Čolović, Mirjana B.
AU  - Ma, Tian
AU  - Ma, Xiang
AU  - Isaković, Anđelka
AU  - Misirlić-Denčić, Sonja
AU  - Kortz, Urlich
AU  - Krstić, Danijela
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13018
AB  - Polyoxopalladates (POPs) are discrete, anionic palladium(II)- oxo nanoclusters combining properties of polyoxometalates and palladium(II), and thus are highly promising for the development of novel antitumor metallodrugs. The aim of this study was to investigate in vitro the influence of three POP salts with approved anti-neuroblastoma action, Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), and Na6[Pd13O8(PhAsO3)8]·23H2O (Pd13L), on E-NTPDase activity using rat synaptic plasma membranes (SPMs) isolated from Wistar brain as a model system. Dose-dependent inhibition of ENTPDases was obtained within concentration range 2 × 10-6 - 1 × 10-3 mol/L for all investigated POPs. Inhibition parameters, IC50 value and Hill's coefficient, nH, were determined by sigmoidal fitting the experimental results. The calculated IC50 values were (1.08 ± 0.25) × 10-4 , (1.19 ± 0.13) × 10-4 , and (2.06 ± 0.88) × 10-4 mol/L for Pd13, SrPd12, and Pd13L, respectively, indicating their similar inhibitory strengths. The nH values were determined to be < 1, indicating negatively cooperative binding for all POPs studied. The observed inhibitory effect of these anti-neuroblastoma POPs on ENTPDase activity suggest that the inhibition of E-NTPDases, the enzymes representing the major part of purinergic signaling, could be considered as a putative mechanism of antitumor action and a new strategy in the development of novel antitumor therapeutics.
PB  - Belgrade : Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Book of abstracts
T1  - Influence of polyoxopalladates(II) on ecto-nucleoside triphosphate diphosphohydrolases
SP  - 77
EP  - 77
UR  - https://hdl.handle.net/21.15107/rcub_vinar_13018
ER  - 

@conference{
author = "Čolović, Mirjana B. and Ma, Tian and Ma, Xiang and Isaković, Anđelka and Misirlić-Denčić, Sonja and Kortz, Urlich and Krstić, Danijela",
year = "2021",
abstract = "Polyoxopalladates (POPs) are discrete, anionic palladium(II)- oxo nanoclusters combining properties of polyoxometalates and palladium(II), and thus are highly promising for the development of novel antitumor metallodrugs. The aim of this study was to investigate in vitro the influence of three POP salts with approved anti-neuroblastoma action, Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), and Na6[Pd13O8(PhAsO3)8]·23H2O (Pd13L), on E-NTPDase activity using rat synaptic plasma membranes (SPMs) isolated from Wistar brain as a model system. Dose-dependent inhibition of ENTPDases was obtained within concentration range 2 × 10-6 - 1 × 10-3 mol/L for all investigated POPs. Inhibition parameters, IC50 value and Hill's coefficient, nH, were determined by sigmoidal fitting the experimental results. The calculated IC50 values were (1.08 ± 0.25) × 10-4 , (1.19 ± 0.13) × 10-4 , and (2.06 ± 0.88) × 10-4 mol/L for Pd13, SrPd12, and Pd13L, respectively, indicating their similar inhibitory strengths. The nH values were determined to be < 1, indicating negatively cooperative binding for all POPs studied. The observed inhibitory effect of these anti-neuroblastoma POPs on ENTPDase activity suggest that the inhibition of E-NTPDases, the enzymes representing the major part of purinergic signaling, could be considered as a putative mechanism of antitumor action and a new strategy in the development of novel antitumor therapeutics.",
publisher = "Belgrade : Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Book of abstracts",
title = "Influence of polyoxopalladates(II) on ecto-nucleoside triphosphate diphosphohydrolases",
pages = "77-77",
url = "https://hdl.handle.net/21.15107/rcub_vinar_13018"
}

Čolović, M. B., Ma, T., Ma, X., Isaković, A., Misirlić-Denčić, S., Kortz, U.,& Krstić, D.. (2021). Influence of polyoxopalladates(II) on ecto-nucleoside triphosphate diphosphohydrolases. in PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Book of abstracts
Belgrade : Society of Physical Chemists of Serbia., 77-77.
https://hdl.handle.net/21.15107/rcub_vinar_13018

Čolović MB, Ma T, Ma X, Isaković A, Misirlić-Denčić S, Kortz U, Krstić D. Influence of polyoxopalladates(II) on ecto-nucleoside triphosphate diphosphohydrolases. in PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Book of abstracts. 2021;:77-77.
https://hdl.handle.net/21.15107/rcub_vinar_13018 .

Čolović, Mirjana B., Ma, Tian, Ma, Xiang, Isaković, Anđelka, Misirlić-Denčić, Sonja, Kortz, Urlich, Krstić, Danijela, "Influence of polyoxopalladates(II) on ecto-nucleoside triphosphate diphosphohydrolases" in PHYSICAL CHEMISTRY 2021 : 15th international conference on fundamental and applied aspects of physical chemistry : Book of abstracts (2021):77-77,
https://hdl.handle.net/21.15107/rcub_vinar_13018 .

TY  - CONF
AU  - Čolović, Mirjana
AU  - Gajski, Goran
AU  - Ma, Tian
AU  - Isaković, Anđelka
AU  - Misirlić-Denčić, Sonja
AU  - Kortz, Urlich
AU  - Krstić, Danijela
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12963
AB  - Polyoxopalladates (POPs) are a subclass of polyoxometalates (POMs) comprising discrete, anionic palladium(II)-oxo complexes. Although numerous studies have been conducted on the biological activity of POMs, their toxicity (e.g. nonselectivity) is frequently a limitation for real-world biomedical applications. Thus, the aim of this study was to evaluate the in vitro safety of the three POPs Pd13 As8 , SrPd12 As6 , and Pd13 (PhAs)8 , which exhibited strong antitumour activity against human neuroblastoma cell line SH-SY5Y, by performing a cyto/genotoxicity study on human healthy blood. Blood samples obtained from a healthy female donor were treated with three different concentrations (12.5, 25, and 50 µmol/L) of the POPs, and incubated at 37 oC for 4 and 24 h. A cytotoxicity (cell viability) assay was performed on isolated human peripheral blood lymphocytes stained with acridine orange and ethidium bromide. A genotoxicity test was carried out on whole blood by alkaline comet assay (microgel electrophoresis), and the percentage of tail DNA was used to assess the level of DNA damage. Pd13 As8 did not affect neither cell viability nor DNA damage, related to the control, at either of the investigated concentrations (after both 4 and 24 h). On the contrary, higher concentrations (25 and 50 µmol/L) of both SrPd12 As6 and Pd13 (PhAs)8 induced a statistically significant decrease in cell viability after 24 h (up to 42 %), and a relative increase of tail DNA (up to 3×) was observed at 50 µmol/L, after 24 h. Therefore, Pd13 As8 could be regarded as non-toxic to human healthy cells, whereas SrPd12 As6 and Pd13 (PhAs)8 require additional toxicity analysis.
PB  - Zagreb, Croatia : Institute for Medical Research and Occupational Health
C3  - Archives of Industrial Hygiene and Toxicology
T1  - Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment
VL  - 72
IS  - Suppl. 1
SP  - 65
EP  - 65
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12963
ER  - 

@conference{
author = "Čolović, Mirjana and Gajski, Goran and Ma, Tian and Isaković, Anđelka and Misirlić-Denčić, Sonja and Kortz, Urlich and Krstić, Danijela",
year = "2021",
abstract = "Polyoxopalladates (POPs) are a subclass of polyoxometalates (POMs) comprising discrete, anionic palladium(II)-oxo complexes. Although numerous studies have been conducted on the biological activity of POMs, their toxicity (e.g. nonselectivity) is frequently a limitation for real-world biomedical applications. Thus, the aim of this study was to evaluate the in vitro safety of the three POPs Pd13 As8 , SrPd12 As6 , and Pd13 (PhAs)8 , which exhibited strong antitumour activity against human neuroblastoma cell line SH-SY5Y, by performing a cyto/genotoxicity study on human healthy blood. Blood samples obtained from a healthy female donor were treated with three different concentrations (12.5, 25, and 50 µmol/L) of the POPs, and incubated at 37 oC for 4 and 24 h. A cytotoxicity (cell viability) assay was performed on isolated human peripheral blood lymphocytes stained with acridine orange and ethidium bromide. A genotoxicity test was carried out on whole blood by alkaline comet assay (microgel electrophoresis), and the percentage of tail DNA was used to assess the level of DNA damage. Pd13 As8 did not affect neither cell viability nor DNA damage, related to the control, at either of the investigated concentrations (after both 4 and 24 h). On the contrary, higher concentrations (25 and 50 µmol/L) of both SrPd12 As6 and Pd13 (PhAs)8 induced a statistically significant decrease in cell viability after 24 h (up to 42 %), and a relative increase of tail DNA (up to 3×) was observed at 50 µmol/L, after 24 h. Therefore, Pd13 As8 could be regarded as non-toxic to human healthy cells, whereas SrPd12 As6 and Pd13 (PhAs)8 require additional toxicity analysis.",
publisher = "Zagreb, Croatia : Institute for Medical Research and Occupational Health",
journal = "Archives of Industrial Hygiene and Toxicology",
title = "Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment",
volume = "72",
number = "Suppl. 1",
pages = "65-65",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12963"
}

Čolović, M., Gajski, G., Ma, T., Isaković, A., Misirlić-Denčić, S., Kortz, U.,& Krstić, D.. (2021). Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment. in Archives of Industrial Hygiene and Toxicology
Zagreb, Croatia : Institute for Medical Research and Occupational Health., 72(Suppl. 1), 65-65.
https://hdl.handle.net/21.15107/rcub_vinar_12963

Čolović M, Gajski G, Ma T, Isaković A, Misirlić-Denčić S, Kortz U, Krstić D. Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment. in Archives of Industrial Hygiene and Toxicology. 2021;72(Suppl. 1):65-65.
https://hdl.handle.net/21.15107/rcub_vinar_12963 .

Čolović, Mirjana, Gajski, Goran, Ma, Tian, Isaković, Anđelka, Misirlić-Denčić, Sonja, Kortz, Urlich, Krstić, Danijela, "Polyoxopalladates as potential antitumor drugs: in vitro toxicity assessment" in Archives of Industrial Hygiene and Toxicology, 72, no. Suppl. 1 (2021):65-65,
https://hdl.handle.net/21.15107/rcub_vinar_12963 .

TY  - JOUR
AU  - Isaković, Anđelka
AU  - Čolović, Mirjana B.
AU  - Ma, Tian
AU  - Ma, Xiang
AU  - Jeremić, Marija
AU  - Gerić, Marko
AU  - Gajski, Goran
AU  - Misirlić-Denčić, Sonja
AU  - Kortz, Ulrich
AU  - Krstić, Danijela Z.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9952
AB  - Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), Na6[Pd13(AsPh)8O32]·23H2O (Pd13L), Na12[SnO8Pd12(PO4)8]·43H2O (SnPd12), and Na12[PbO8Pd12(PO4)8]·38H2O (PbPd12)), as the largest subset of PONMs. A pure inorganic, Pd13, was found as the most potent and selective antineuroblastoma agent with IC50 values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC50 values (µM) for 24/48 h treatment with SrPd12 and Pd13L were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas SnPd12 and PbPd12 did not remarkably affect the SH-SY5Y viability (IC50 > > 100 µM). Pd13 caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly, Pd13 demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary, SrPd12 and Pd13L at concentrations ≥ 1/3 IC50 (24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control. SnPd12 and PbPd12, previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.
T2  - JBIC Journal of Biological Inorganic Chemistry
T1  - Selected polyoxopalladates as promising and selective antitumor drug candidates
VL  - 26
IS  - 8
SP  - 957
EP  - 971
DO  - 10.1007/s00775-021-01905-4
ER  - 

@article{
author = "Isaković, Anđelka and Čolović, Mirjana B. and Ma, Tian and Ma, Xiang and Jeremić, Marija and Gerić, Marko and Gajski, Goran and Misirlić-Denčić, Sonja and Kortz, Ulrich and Krstić, Danijela Z.",
year = "2021",
abstract = "Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na8[Pd13As8O34(OH)6]·42H2O (Pd13), Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3]·2NaOAc·32H2O (SrPd12), Na6[Pd13(AsPh)8O32]·23H2O (Pd13L), Na12[SnO8Pd12(PO4)8]·43H2O (SnPd12), and Na12[PbO8Pd12(PO4)8]·38H2O (PbPd12)), as the largest subset of PONMs. A pure inorganic, Pd13, was found as the most potent and selective antineuroblastoma agent with IC50 values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC50 values (µM) for 24/48 h treatment with SrPd12 and Pd13L were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas SnPd12 and PbPd12 did not remarkably affect the SH-SY5Y viability (IC50 > > 100 µM). Pd13 caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly, Pd13 demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary, SrPd12 and Pd13L at concentrations ≥ 1/3 IC50 (24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control. SnPd12 and PbPd12, previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.",
journal = "JBIC Journal of Biological Inorganic Chemistry",
title = "Selected polyoxopalladates as promising and selective antitumor drug candidates",
volume = "26",
number = "8",
pages = "957-971",
doi = "10.1007/s00775-021-01905-4"
}

Isaković, A., Čolović, M. B., Ma, T., Ma, X., Jeremić, M., Gerić, M., Gajski, G., Misirlić-Denčić, S., Kortz, U.,& Krstić, D. Z.. (2021). Selected polyoxopalladates as promising and selective antitumor drug candidates. in JBIC Journal of Biological Inorganic Chemistry, 26(8), 957-971.
https://doi.org/10.1007/s00775-021-01905-4

Isaković A, Čolović MB, Ma T, Ma X, Jeremić M, Gerić M, Gajski G, Misirlić-Denčić S, Kortz U, Krstić DZ. Selected polyoxopalladates as promising and selective antitumor drug candidates. in JBIC Journal of Biological Inorganic Chemistry. 2021;26(8):957-971.
doi:10.1007/s00775-021-01905-4 .

Isaković, Anđelka, Čolović, Mirjana B., Ma, Tian, Ma, Xiang, Jeremić, Marija, Gerić, Marko, Gajski, Goran, Misirlić-Denčić, Sonja, Kortz, Ulrich, Krstić, Danijela Z., "Selected polyoxopalladates as promising and selective antitumor drug candidates" in JBIC Journal of Biological Inorganic Chemistry, 26, no. 8 (2021):957-971,
https://doi.org/10.1007/s00775-021-01905-4 . .

TY  - JOUR
AU  - Yang, Peng
AU  - Ma, Tian
AU  - Lang, Zhongling
AU  - Misirlić-Denčić, Sonja
AU  - Isaković, Anđelka
AU  - Benyei, Attila
AU  - Čolović, Mirjana B.
AU  - Marković, Ivanka
AU  - Krstić, Danijela Z.
AU  - Poblet, Josep M.
AU  - Lin, Zhengguo
AU  - Kortz, Ulrich
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8499
AB  - The first two examples of polyoxopalladates(II) (POPs) containing tetravalent metal ion guests, [MO8Pd12(PO4)8]12- (M = SnIV, PbIV), have been prepared and structurally characterized in the solid state, solution, and gas phase. The interactions of the metal ion guests and the palladium-oxo shell were studied by theoretical calculations. The POPs were shown to possess anticancer activity by causing oxidative stress inducing caspase activation and consecutive apoptosis of leukemic cells.
T2  - Inorganic Chemistry
T1  - Tetravalent Metal Ion Guests in Polyoxopalladate Chemistry: Synthesis and Anticancer Activity of [MO8Pd12(PO4)8]12-(M=SnIV, PbIV)
VL  - 58
IS  - 17
SP  - 11294
EP  - 11299
DO  - 10.1021/acs.inorgchem.9b01129
ER  - 

@article{
author = "Yang, Peng and Ma, Tian and Lang, Zhongling and Misirlić-Denčić, Sonja and Isaković, Anđelka and Benyei, Attila and Čolović, Mirjana B. and Marković, Ivanka and Krstić, Danijela Z. and Poblet, Josep M. and Lin, Zhengguo and Kortz, Ulrich",
year = "2019",
abstract = "The first two examples of polyoxopalladates(II) (POPs) containing tetravalent metal ion guests, [MO8Pd12(PO4)8]12- (M = SnIV, PbIV), have been prepared and structurally characterized in the solid state, solution, and gas phase. The interactions of the metal ion guests and the palladium-oxo shell were studied by theoretical calculations. The POPs were shown to possess anticancer activity by causing oxidative stress inducing caspase activation and consecutive apoptosis of leukemic cells.",
journal = "Inorganic Chemistry",
title = "Tetravalent Metal Ion Guests in Polyoxopalladate Chemistry: Synthesis and Anticancer Activity of [MO8Pd12(PO4)8]12-(M=SnIV, PbIV)",
volume = "58",
number = "17",
pages = "11294-11299",
doi = "10.1021/acs.inorgchem.9b01129"
}

Yang, P., Ma, T., Lang, Z., Misirlić-Denčić, S., Isaković, A., Benyei, A., Čolović, M. B., Marković, I., Krstić, D. Z., Poblet, J. M., Lin, Z.,& Kortz, U.. (2019). Tetravalent Metal Ion Guests in Polyoxopalladate Chemistry: Synthesis and Anticancer Activity of [MO8Pd12(PO4)8]12-(M=SnIV, PbIV). in Inorganic Chemistry, 58(17), 11294-11299.
https://doi.org/10.1021/acs.inorgchem.9b01129

Yang P, Ma T, Lang Z, Misirlić-Denčić S, Isaković A, Benyei A, Čolović MB, Marković I, Krstić DZ, Poblet JM, Lin Z, Kortz U. Tetravalent Metal Ion Guests in Polyoxopalladate Chemistry: Synthesis and Anticancer Activity of [MO8Pd12(PO4)8]12-(M=SnIV, PbIV). in Inorganic Chemistry. 2019;58(17):11294-11299.
doi:10.1021/acs.inorgchem.9b01129 .

Yang, Peng, Ma, Tian, Lang, Zhongling, Misirlić-Denčić, Sonja, Isaković, Anđelka, Benyei, Attila, Čolović, Mirjana B., Marković, Ivanka, Krstić, Danijela Z., Poblet, Josep M., Lin, Zhengguo, Kortz, Ulrich, "Tetravalent Metal Ion Guests in Polyoxopalladate Chemistry: Synthesis and Anticancer Activity of [MO8Pd12(PO4)8]12-(M=SnIV, PbIV)" in Inorganic Chemistry, 58, no. 17 (2019):11294-11299,
https://doi.org/10.1021/acs.inorgchem.9b01129 . .