TY  - CONF
AU  - Jeremić, Marija
AU  - Isaković, Anđelka
AU  - Krstić, Danijela
AU  - Čolović, Mirjana
AU  - Kortz, Ulrich
AU  - Misirlić-Denčić, Sonja
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12965
AB  - Background: Polyoxo-noble-metalates, 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 nextgeneration antitumor metallodrugs. The aim of this study was to evaluate the antineuroblastoma potential of three novel polyoxopalladates. Material and methods: All experiments were performed on human neuroblastoma cell line, SHSY5Y. The three polyoxo-noble-palladates Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3] ・2NaOAc・32H2O (SrPd12), Na12[SnIVO8Pd12(PO4)8]·43H2O (SnPd12) and Na12[PbIVO8Pd12(PO4)8]·38H2O (PbPd12) were investigated in our study. The viability of neuroblastoma cells after 24h treatment was assessed using an acid phosphatase assay. The level of superoxide ion, mitochondrial membrane potential, pan-caspase activity, cell cycle analysis and acidic vesicles content were determined by flow cytometry using appropriate fluorochromes. Results: Calculated IC50 (μM; 24h) values were 75.8 ± 6.7 (SrPd12) and >>100 (SnPd12 and PbPd12), selecting SrPd12 as the most efficient. SrPd12 did not affect the mitochondrial membrane potential and superoxide production in neuroblastoma cells after short (2 h and 4 h) exposure. Also, it did not induce an increase in the number of neuroblastoma cells with fragmented DNA content, but displayed the cell cycle arrest: the ~ 23% reduction of neuroblastoma cells in G0/G1 phase and the ~ 17% increase in S phase. The treatment with SrPd12 did not increase the level of acidic vesicles but it increased the activity of caspases five-fold. Conclusion: Only SrPd12 exhibited a satisfactory antineuroblastoma action by inducing caspase activation and neuroblastoma cell cycle arrest.
PB  - Belgrade : Serbian Association for Cancer Research (SDIR)
C3  - SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts
T1  - Selected polyoxopalladates as potential antitumor drug candidates
SP  - 70
EP  - 70
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12965
ER  - 

@conference{
author = "Jeremić, Marija and Isaković, Anđelka and Krstić, Danijela and Čolović, Mirjana and Kortz, Ulrich and Misirlić-Denčić, Sonja",
year = "2021",
abstract = "Background: Polyoxo-noble-metalates, 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 nextgeneration antitumor metallodrugs. The aim of this study was to evaluate the antineuroblastoma potential of three novel polyoxopalladates. Material and methods: All experiments were performed on human neuroblastoma cell line, SHSY5Y. The three polyoxo-noble-palladates Na4[SrPd12O6(OH)3(PhAsO3)6(OAc)3] ・2NaOAc・32H2O (SrPd12), Na12[SnIVO8Pd12(PO4)8]·43H2O (SnPd12) and Na12[PbIVO8Pd12(PO4)8]·38H2O (PbPd12) were investigated in our study. The viability of neuroblastoma cells after 24h treatment was assessed using an acid phosphatase assay. The level of superoxide ion, mitochondrial membrane potential, pan-caspase activity, cell cycle analysis and acidic vesicles content were determined by flow cytometry using appropriate fluorochromes. Results: Calculated IC50 (μM; 24h) values were 75.8 ± 6.7 (SrPd12) and >>100 (SnPd12 and PbPd12), selecting SrPd12 as the most efficient. SrPd12 did not affect the mitochondrial membrane potential and superoxide production in neuroblastoma cells after short (2 h and 4 h) exposure. Also, it did not induce an increase in the number of neuroblastoma cells with fragmented DNA content, but displayed the cell cycle arrest: the ~ 23% reduction of neuroblastoma cells in G0/G1 phase and the ~ 17% increase in S phase. The treatment with SrPd12 did not increase the level of acidic vesicles but it increased the activity of caspases five-fold. Conclusion: Only SrPd12 exhibited a satisfactory antineuroblastoma action by inducing caspase activation and neuroblastoma cell cycle arrest.",
publisher = "Belgrade : Serbian Association for Cancer Research (SDIR)",
journal = "SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts",
title = "Selected polyoxopalladates as potential antitumor drug candidates",
pages = "70-70",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12965"
}

Jeremić, M., Isaković, A., Krstić, D., Čolović, M., Kortz, U.,& Misirlić-Denčić, S.. (2021). Selected polyoxopalladates as potential antitumor drug candidates. in SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts
Belgrade : Serbian Association for Cancer Research (SDIR)., 70-70.
https://hdl.handle.net/21.15107/rcub_vinar_12965

Jeremić M, Isaković A, Krstić D, Čolović M, Kortz U, Misirlić-Denčić S. Selected polyoxopalladates as potential antitumor drug candidates. in SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts. 2021;:70-70.
https://hdl.handle.net/21.15107/rcub_vinar_12965 .

Jeremić, Marija, Isaković, Anđelka, Krstić, Danijela, Čolović, Mirjana, Kortz, Ulrich, Misirlić-Denčić, Sonja, "Selected polyoxopalladates as potential antitumor drug candidates" in SDIR- 5 : 5th Congress of the serbian association for cancer research : Book of abstracts (2021):70-70,
https://hdl.handle.net/21.15107/rcub_vinar_12965 .

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  - Čolović, Mirjana B.
AU  - Lacković, Milan
AU  - Lalatović, Jovana
AU  - Mougharbel, Ali S.
AU  - Kortz, Ulrich
AU  - Krstić, Danijela Z.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10139
AB  - Background: Polyoxometalates (POMs) are negatively charged metal-oxo clusters of early transition metal ions in high oxidation states (e.g., WVI, MoVI, VV). POMs are of interest in the fields of catalysis, electronics, magnetic materials and nanotechnology. Moreover, POMs were shown to exhibit biological activities in vitro and in vivo, such as antitumor, antimicrobial, and antidiabetic. Methods: The literature search for this peer-reviewed article was performed using PubMed and Scopus databases with the help of appropriate keywords. Results: This review gives a comprehensive overview of recent studies regarding biological activities of polyoxometalates, and their biomedical applications as promising anti-viral, anti-bacterial, anti-tumor, and anti-diabetic agents. Additionally, their putative mechanisms of action and molecular targets are particularly considered. Conclusion: Although a wide range of biological activities of Polyoxometalates (POMs) has been reported, they are to the best of our knowledge not close to a clinical trial or a final application in the treatment of diabetes or infectious and malignant diseases. Accordingly, further studies should be directed towards determining the mechanism of POM biological actions, which would enable fine-tuning at the molecular level, and consequently efficient action towards biological targets and as low toxicity as possible. Furthermore, biomedical studies should be performed on solution-stable POMs employing physiological conditions and concentrations.
T2  - Current Medicinal Chemistry
T1  - Polyoxometalates in Biomedicine: Update and Overview
VL  - 27
IS  - 3
SP  - 362
EP  - 379
DO  - 10.2174/0929867326666190827153532
ER  - 

@article{
author = "Čolović, Mirjana B. and Lacković, Milan and Lalatović, Jovana and Mougharbel, Ali S. and Kortz, Ulrich and Krstić, Danijela Z.",
year = "2020",
abstract = "Background: Polyoxometalates (POMs) are negatively charged metal-oxo clusters of early transition metal ions in high oxidation states (e.g., WVI, MoVI, VV). POMs are of interest in the fields of catalysis, electronics, magnetic materials and nanotechnology. Moreover, POMs were shown to exhibit biological activities in vitro and in vivo, such as antitumor, antimicrobial, and antidiabetic. Methods: The literature search for this peer-reviewed article was performed using PubMed and Scopus databases with the help of appropriate keywords. Results: This review gives a comprehensive overview of recent studies regarding biological activities of polyoxometalates, and their biomedical applications as promising anti-viral, anti-bacterial, anti-tumor, and anti-diabetic agents. Additionally, their putative mechanisms of action and molecular targets are particularly considered. Conclusion: Although a wide range of biological activities of Polyoxometalates (POMs) has been reported, they are to the best of our knowledge not close to a clinical trial or a final application in the treatment of diabetes or infectious and malignant diseases. Accordingly, further studies should be directed towards determining the mechanism of POM biological actions, which would enable fine-tuning at the molecular level, and consequently efficient action towards biological targets and as low toxicity as possible. Furthermore, biomedical studies should be performed on solution-stable POMs employing physiological conditions and concentrations.",
journal = "Current Medicinal Chemistry",
title = "Polyoxometalates in Biomedicine: Update and Overview",
volume = "27",
number = "3",
pages = "362-379",
doi = "10.2174/0929867326666190827153532"
}

Čolović, M. B., Lacković, M., Lalatović, J., Mougharbel, A. S., Kortz, U.,& Krstić, D. Z.. (2020). Polyoxometalates in Biomedicine: Update and Overview. in Current Medicinal Chemistry, 27(3), 362-379.
https://doi.org/10.2174/0929867326666190827153532

Čolović MB, Lacković M, Lalatović J, Mougharbel AS, Kortz U, Krstić DZ. Polyoxometalates in Biomedicine: Update and Overview. in Current Medicinal Chemistry. 2020;27(3):362-379.
doi:10.2174/0929867326666190827153532 .

Čolović, Mirjana B., Lacković, Milan, Lalatović, Jovana, Mougharbel, Ali S., Kortz, Ulrich, Krstić, Danijela Z., "Polyoxometalates in Biomedicine: Update and Overview" in Current Medicinal Chemistry, 27, no. 3 (2020):362-379,
https://doi.org/10.2174/0929867326666190827153532 . .

TY  - CONF
AU  - Dinčić, Marko
AU  - Sarić, Marija
AU  - Čolović, Mirjana
AU  - Todorović, Jasna
AU  - Ignjatović, Svetlana
AU  - Radosavljević, Branimir
AU  - Mougharbel, Ali S.
AU  - Kortz, Ulrich
AU  - Krstić, Danijela
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12962
AB  - Introduction. Polyoxometalates (POMs) are negatively charged inorganic aggregates that possess potential antibacterial, anticancer, antidiabetic and antiviral effects. Although toxicity evaluation of drug candidates is necessary, reports of relevant toxicological studies of these compounds are relatively rare.  Aims. Since our preliminary results demonstrated biological activities of the donut-shaped POM {NaP5W30} (POM1) and the Ag + -containing derivative POM {AgP5W30} (POM2), the aim of present study was to evaluate their toxicological effects in vivo, using Wistar albino rats as an experimental model.  Methods. Animals (n = 6 per group) were orally treated with investigated POMs in daily doses of 20 mg/kg body weight for 14 days when the rats were sacrificed and blood samples were collected. The biochemical markers of renal (serum concentrations of urea - SUr and creatinine - SCr) and liver function (serum concentrations of total protein–TP and albumin - Alb, serum activities of aspartate aminotransferase - AST and alanine transaminase - ALT) were determined spectrophotometrically.  Results. The POM1 and POM2 were induced statistically significant increasing of SUr (in: mmol/L) (7.95 ± 0.35 and 6.83 ± 0.26 vs. 4.97 ± 0.47; p < 0.001 and p < 0.01, respectively) and SCr (in: mmol/L) (41.34 ± 0.84 and 39.06 ± 1.07 vs. 32.27 ± 0.61; p < 0.001 and p < 0.001, respectively) compared to the control group. Also, investigated compounds induced statistically significant decreasing of TP (in: g/L) (60.16 ± 1.43 and 58.53 ± 0.81 vs. 67.86 ± 0.03; p < 0.001 and p < 0.001, respectively) and Alb (in: g/L) (29.34 ± 0.58 and 29.45 ± 0.81 vs. 34.89 ± 0.41; p < 0.001 and p < 0.001, respectively) compared to the control group. In contrast, there was no statistically significant difference in AST and ALT between the untreated and treated groups (p > 0.05).  Conclusion. Obtained results suggested that both investigated POMs induce kidney injury as well as synthetic dysfunction of liver. Thus, their potential clinical application would require a more complex toxicological study.
C3  - Pathophysiology
T1  - Toxicity evaluation of two biologically active polyoxotungstates
VL  - 25
IS  - 3
SP  - 243
EP  - 244
DO  - 10.1016/j.pathophys.2018.07.177
ER  - 

@conference{
author = "Dinčić, Marko and Sarić, Marija and Čolović, Mirjana and Todorović, Jasna and Ignjatović, Svetlana and Radosavljević, Branimir and Mougharbel, Ali S. and Kortz, Ulrich and Krstić, Danijela",
year = "2018",
abstract = "Introduction. Polyoxometalates (POMs) are negatively charged inorganic aggregates that possess potential antibacterial, anticancer, antidiabetic and antiviral effects. Although toxicity evaluation of drug candidates is necessary, reports of relevant toxicological studies of these compounds are relatively rare.  Aims. Since our preliminary results demonstrated biological activities of the donut-shaped POM {NaP5W30} (POM1) and the Ag + -containing derivative POM {AgP5W30} (POM2), the aim of present study was to evaluate their toxicological effects in vivo, using Wistar albino rats as an experimental model.  Methods. Animals (n = 6 per group) were orally treated with investigated POMs in daily doses of 20 mg/kg body weight for 14 days when the rats were sacrificed and blood samples were collected. The biochemical markers of renal (serum concentrations of urea - SUr and creatinine - SCr) and liver function (serum concentrations of total protein–TP and albumin - Alb, serum activities of aspartate aminotransferase - AST and alanine transaminase - ALT) were determined spectrophotometrically.  Results. The POM1 and POM2 were induced statistically significant increasing of SUr (in: mmol/L) (7.95 ± 0.35 and 6.83 ± 0.26 vs. 4.97 ± 0.47; p < 0.001 and p < 0.01, respectively) and SCr (in: mmol/L) (41.34 ± 0.84 and 39.06 ± 1.07 vs. 32.27 ± 0.61; p < 0.001 and p < 0.001, respectively) compared to the control group. Also, investigated compounds induced statistically significant decreasing of TP (in: g/L) (60.16 ± 1.43 and 58.53 ± 0.81 vs. 67.86 ± 0.03; p < 0.001 and p < 0.001, respectively) and Alb (in: g/L) (29.34 ± 0.58 and 29.45 ± 0.81 vs. 34.89 ± 0.41; p < 0.001 and p < 0.001, respectively) compared to the control group. In contrast, there was no statistically significant difference in AST and ALT between the untreated and treated groups (p > 0.05).  Conclusion. Obtained results suggested that both investigated POMs induce kidney injury as well as synthetic dysfunction of liver. Thus, their potential clinical application would require a more complex toxicological study.",
journal = "Pathophysiology",
title = "Toxicity evaluation of two biologically active polyoxotungstates",
volume = "25",
number = "3",
pages = "243-244",
doi = "10.1016/j.pathophys.2018.07.177"
}

Dinčić, M., Sarić, M., Čolović, M., Todorović, J., Ignjatović, S., Radosavljević, B., Mougharbel, A. S., Kortz, U.,& Krstić, D.. (2018). Toxicity evaluation of two biologically active polyoxotungstates. in Pathophysiology, 25(3), 243-244.
https://doi.org/10.1016/j.pathophys.2018.07.177

Dinčić M, Sarić M, Čolović M, Todorović J, Ignjatović S, Radosavljević B, Mougharbel AS, Kortz U, Krstić D. Toxicity evaluation of two biologically active polyoxotungstates. in Pathophysiology. 2018;25(3):243-244.
doi:10.1016/j.pathophys.2018.07.177 .

Dinčić, Marko, Sarić, Marija, Čolović, Mirjana, Todorović, Jasna, Ignjatović, Svetlana, Radosavljević, Branimir, Mougharbel, Ali S., Kortz, Ulrich, Krstić, Danijela, "Toxicity evaluation of two biologically active polyoxotungstates" in Pathophysiology, 25, no. 3 (2018):243-244,
https://doi.org/10.1016/j.pathophys.2018.07.177 . .