TY  - JOUR
AU  - Drača, Dijana
AU  - Marković, Milan
AU  - Gozzi, Marta
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4425
AB  - Gliomas and glioblastomas are very aggressive forms of brain tumors, prone to the devel opment of a multitude of resistance mechanisms to therapeutic treatments, including cytoprotective
autophagy. In this work, we investigated the role and mechanism of action of the combination of a
ruthenacarborane derivative with 8-hydroxyquinoline (8-HQ), linked via an ester bond (complex 2),
in rat astrocytoma C6 and human glioma U251 cells, in comparison with the two compounds alone,
i.e., the free carboxylic acid (complex 1) and 8-HQ, and their non-covalent combination ([1 + 8-HQ],
in 1:1 molar ratio). We found that only complex 2 was able to significantly affect cellular viability
in glioma U251 cells (IC50 11.4 µM) via inhibition of the autophagic machinery, most likely acting
at the early stages of the autophagic cascade. Contrary to 8-HQ alone, complex 2 was also able
to impair cellular viability under conditions of glucose deprivation. We thus suggest different
mechanisms of action of ruthenacarborane complex 2 than purely organic quinoline-based drugs,
making complex 2 a very attractive candidate for evading the known resistances of brain tumors to
chloroquine-based therapies.
PB  - Basel: MDPI
T2  - Molecules
T1  - Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors
IS  - 13
VL  - 26
DO  - 10.3390/molecules26133801
SP  - 3801
ER  - 

@article{
author = "Drača, Dijana and Marković, Milan and Gozzi, Marta and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2021",
abstract = "Gliomas and glioblastomas are very aggressive forms of brain tumors, prone to the devel opment of a multitude of resistance mechanisms to therapeutic treatments, including cytoprotective
autophagy. In this work, we investigated the role and mechanism of action of the combination of a
ruthenacarborane derivative with 8-hydroxyquinoline (8-HQ), linked via an ester bond (complex 2),
in rat astrocytoma C6 and human glioma U251 cells, in comparison with the two compounds alone,
i.e., the free carboxylic acid (complex 1) and 8-HQ, and their non-covalent combination ([1 + 8-HQ],
in 1:1 molar ratio). We found that only complex 2 was able to significantly affect cellular viability
in glioma U251 cells (IC50 11.4 µM) via inhibition of the autophagic machinery, most likely acting
at the early stages of the autophagic cascade. Contrary to 8-HQ alone, complex 2 was also able
to impair cellular viability under conditions of glucose deprivation. We thus suggest different
mechanisms of action of ruthenacarborane complex 2 than purely organic quinoline-based drugs,
making complex 2 a very attractive candidate for evading the known resistances of brain tumors to
chloroquine-based therapies.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors",
number = "13",
volume = "26",
doi = "10.3390/molecules26133801",
pages = "3801"
}

Drača, D., Marković, M., Gozzi, M., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2021). Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors. in Molecules
Basel: MDPI., 26(13), 3801.
https://doi.org/10.3390/molecules26133801

Drača D, Marković M, Gozzi M, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors. in Molecules. 2021;26(13):3801.
doi:10.3390/molecules26133801 .

Drača, Dijana, Marković, Milan, Gozzi, Marta, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors" in Molecules, 26, no. 13 (2021):3801,
https://doi.org/10.3390/molecules26133801 . .

TY  - JOUR
AU  - Gozzi, Marta
AU  - Murganic, Blagoje
AU  - Drača, Dijana
AU  - Popp, John
AU  - Coburger, Peter
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
PY  - 2019
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201900349
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3534
AB  - The role of autophagy in cancer is often complex, ranging from tumor-promoting to -suppressing effects. In this study, two novel hybrid molecules were designed, containing a ruthenacarborane fragment conjugated with a known modulator of autophagy, namely a quinoline derivative. The complex closo-[3-(η6 -p-cymene)-1-(quinolin-8-yl-acetate)-3,1,2-RuC2 B9 H10 ] (4) showed a dual mode of action against the LN229 (human glioblastoma) cell line, where it inhibited tumor-promoting autophagy, and strongly inhibited cell proliferation, de facto blocking cellular division. These results, together with the tendency to spontaneously form nanoparticles in aqueous solution, make complex 4 a very promising drug candidate for further studies in vivo, for the treatment of autophagy-prone glioblastomas.
T2  - ChemMedChem
T1  - Quinoline-Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action.
DO  - 10.1002/cmdc.201900349
ER  - 

@article{
author = "Gozzi, Marta and Murganic, Blagoje and Drača, Dijana and Popp, John and Coburger, Peter and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Hey-Hawkins, Evamarie",
year = "2019",
abstract = "The role of autophagy in cancer is often complex, ranging from tumor-promoting to -suppressing effects. In this study, two novel hybrid molecules were designed, containing a ruthenacarborane fragment conjugated with a known modulator of autophagy, namely a quinoline derivative. The complex closo-[3-(η6 -p-cymene)-1-(quinolin-8-yl-acetate)-3,1,2-RuC2 B9 H10 ] (4) showed a dual mode of action against the LN229 (human glioblastoma) cell line, where it inhibited tumor-promoting autophagy, and strongly inhibited cell proliferation, de facto blocking cellular division. These results, together with the tendency to spontaneously form nanoparticles in aqueous solution, make complex 4 a very promising drug candidate for further studies in vivo, for the treatment of autophagy-prone glioblastomas.",
journal = "ChemMedChem",
title = "Quinoline-Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action.",
doi = "10.1002/cmdc.201900349"
}

Gozzi, M., Murganic, B., Drača, D., Popp, J., Coburger, P., Maksimović-Ivanić, D., Mijatović, S.,& Hey-Hawkins, E.. (2019). Quinoline-Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action.. in ChemMedChem.
https://doi.org/10.1002/cmdc.201900349

Gozzi M, Murganic B, Drača D, Popp J, Coburger P, Maksimović-Ivanić D, Mijatović S, Hey-Hawkins E. Quinoline-Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action.. in ChemMedChem. 2019;.
doi:10.1002/cmdc.201900349 .

Gozzi, Marta, Murganic, Blagoje, Drača, Dijana, Popp, John, Coburger, Peter, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Hey-Hawkins, Evamarie, "Quinoline-Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action." in ChemMedChem (2019),
https://doi.org/10.1002/cmdc.201900349 . .

TY  - JOUR
AU  - Gozzi, Marta
AU  - Schwarze, Benedikt
AU  - Sárosi, Menyhárt-Botond
AU  - Lönnecke, Peter
AU  - Drača, Dijana
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
PY  - 2017
UR  - http://xlink.rsc.org/?DOI=C7DT02027A
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2858
AB  - Three [(η6-arene)RuC2B9H11] complexes (arene = p-cymene (2), biphenyl (3) and 1-Me-4-COOEt-C6H4 (4)) were synthesised according to modified literature procedures and fully characterised. 2-4 were found to be moderately active against two types of tumour cell lines (HCT116 and MCF7), with IC50 values in the low micromolar range. However, viability of normal, healthy cells (MRC-5 cell line, MLEC and mouse macrophages) was not affected by treatment with 2-4, indicating high selectivity of the metallacarborane complexes towards tumour cell lines, compared to the unselective antitumour agent cisplatin and other potential RuII drugs. Moreover, flow cytometric analysis suggested that 4 induces cell death via a caspase-dependent apoptotic mechanism. DFT calculations of the frontier molecular orbitals showed that the HOMO-LUMO gap in 2-4 is smaller than in the corresponding cyclopentadienyl complexes 2-Cp-4-Cp (e.g. 5.47 (2) vs. 6.31 eV (2-Cp)). In order to assess the stability of 2-4, particularly the ruthenium-dicarbollide bond, energy decomposition analysis (EDA) of 2-4, together with the respective cyclopentadienyl analogues 2-Cp-4-Cp, was performed. EDA suggests that the ruthenium(ii)-dicarbollide bond in the three complexes is mostly ionic and far stronger than the ruthenium(ii)-arene bond.
T2  - Dalton Transactions
T1  - Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines
IS  - 36
VL  - 46
DO  - 10.1039/C7DT02027A
SP  - 12067
EP  - 12080
ER  - 

@article{
author = "Gozzi, Marta and Schwarze, Benedikt and Sárosi, Menyhárt-Botond and Lönnecke, Peter and Drača, Dijana and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Hey-Hawkins, Evamarie",
year = "2017",
abstract = "Three [(η6-arene)RuC2B9H11] complexes (arene = p-cymene (2), biphenyl (3) and 1-Me-4-COOEt-C6H4 (4)) were synthesised according to modified literature procedures and fully characterised. 2-4 were found to be moderately active against two types of tumour cell lines (HCT116 and MCF7), with IC50 values in the low micromolar range. However, viability of normal, healthy cells (MRC-5 cell line, MLEC and mouse macrophages) was not affected by treatment with 2-4, indicating high selectivity of the metallacarborane complexes towards tumour cell lines, compared to the unselective antitumour agent cisplatin and other potential RuII drugs. Moreover, flow cytometric analysis suggested that 4 induces cell death via a caspase-dependent apoptotic mechanism. DFT calculations of the frontier molecular orbitals showed that the HOMO-LUMO gap in 2-4 is smaller than in the corresponding cyclopentadienyl complexes 2-Cp-4-Cp (e.g. 5.47 (2) vs. 6.31 eV (2-Cp)). In order to assess the stability of 2-4, particularly the ruthenium-dicarbollide bond, energy decomposition analysis (EDA) of 2-4, together with the respective cyclopentadienyl analogues 2-Cp-4-Cp, was performed. EDA suggests that the ruthenium(ii)-dicarbollide bond in the three complexes is mostly ionic and far stronger than the ruthenium(ii)-arene bond.",
journal = "Dalton Transactions",
title = "Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines",
number = "36",
volume = "46",
doi = "10.1039/C7DT02027A",
pages = "12067-12080"
}

Gozzi, M., Schwarze, B., Sárosi, M., Lönnecke, P., Drača, D., Maksimović-Ivanić, D., Mijatović, S.,& Hey-Hawkins, E.. (2017). Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines. in Dalton Transactions, 46(36), 12067-12080.
https://doi.org/10.1039/C7DT02027A

Gozzi M, Schwarze B, Sárosi M, Lönnecke P, Drača D, Maksimović-Ivanić D, Mijatović S, Hey-Hawkins E. Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines. in Dalton Transactions. 2017;46(36):12067-12080.
doi:10.1039/C7DT02027A .

Gozzi, Marta, Schwarze, Benedikt, Sárosi, Menyhárt-Botond, Lönnecke, Peter, Drača, Dijana, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Hey-Hawkins, Evamarie, "Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines" in Dalton Transactions, 46, no. 36 (2017):12067-12080,
https://doi.org/10.1039/C7DT02027A . .

TY  - GEN
AU  - Gozzi, Marta
AU  - Schwarze, Benedikt
AU  - Sárosi, Menyhárt-Botond
AU  - Lönnecke, Peter
AU  - Drača, Dijana
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
PY  - 2017
UR  - http://xlink.rsc.org/?DOI=C7DT02027A
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2848
AB  - Three [(η6-arene)RuC2B9H11] complexes (arene = p-cymene (2), biphenyl (3) and 1-Me-4-COOEt-C6H4 (4)) were synthesised according to modified literature procedures and fully characterised. 2–4 were found to be moderately active against two types of tumour cell lines (HCT116 and MCF7), with IC50 values in the low micromolar range. However, viability of normal, healthy cells (MRC-5 cell line, MLEC and mouse macrophages) was not affected by treatment with 2–4, indicating high selectivity of the metallacarborane complexes towards tumour cell lines, compared to the unselective antitumour agent cisplatin and other potential RuII drugs. Moreover, flow cytometric analysis suggested that 4 induces cell death via a caspase-dependent apoptotic mechanism. DFT calculations of the frontier molecular orbitals showed that the HOMO–LUMO gap in 2–4 is smaller than in the corresponding cyclopentadienyl complexes 2-Cp–4-Cp (e.g. 5.47 (2) vs. 6.31 eV (2-Cp)). In order to assess the stability of 2–4, particularly the ruthenium–dicarbollide bond, energy decomposition analysis (EDA) of 2–4, together with the respective cyclopentadienyl analogues 2-Cp–4-Cp, was performed. EDA suggests that the ruthenium(II)–dicarbollide bond in the three complexes is mostly ionic and far stronger than the ruthenium(II)–arene bond.
PB  - The Royal Society of Chemistry
T2  - Dalton Transactions
T1  - Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines
DO  - 10.1039/C7DT02027A
ER  - 

@misc{
author = "Gozzi, Marta and Schwarze, Benedikt and Sárosi, Menyhárt-Botond and Lönnecke, Peter and Drača, Dijana and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Hey-Hawkins, Evamarie",
year = "2017",
abstract = "Three [(η6-arene)RuC2B9H11] complexes (arene = p-cymene (2), biphenyl (3) and 1-Me-4-COOEt-C6H4 (4)) were synthesised according to modified literature procedures and fully characterised. 2–4 were found to be moderately active against two types of tumour cell lines (HCT116 and MCF7), with IC50 values in the low micromolar range. However, viability of normal, healthy cells (MRC-5 cell line, MLEC and mouse macrophages) was not affected by treatment with 2–4, indicating high selectivity of the metallacarborane complexes towards tumour cell lines, compared to the unselective antitumour agent cisplatin and other potential RuII drugs. Moreover, flow cytometric analysis suggested that 4 induces cell death via a caspase-dependent apoptotic mechanism. DFT calculations of the frontier molecular orbitals showed that the HOMO–LUMO gap in 2–4 is smaller than in the corresponding cyclopentadienyl complexes 2-Cp–4-Cp (e.g. 5.47 (2) vs. 6.31 eV (2-Cp)). In order to assess the stability of 2–4, particularly the ruthenium–dicarbollide bond, energy decomposition analysis (EDA) of 2–4, together with the respective cyclopentadienyl analogues 2-Cp–4-Cp, was performed. EDA suggests that the ruthenium(II)–dicarbollide bond in the three complexes is mostly ionic and far stronger than the ruthenium(II)–arene bond.",
publisher = "The Royal Society of Chemistry",
journal = "Dalton Transactions",
title = "Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines",
doi = "10.1039/C7DT02027A"
}

Gozzi, M., Schwarze, B., Sárosi, M., Lönnecke, P., Drača, D., Maksimović-Ivanić, D., Mijatović, S.,& Hey-Hawkins, E.. (2017). Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines. in Dalton Transactions
The Royal Society of Chemistry..
https://doi.org/10.1039/C7DT02027A

Gozzi M, Schwarze B, Sárosi M, Lönnecke P, Drača D, Maksimović-Ivanić D, Mijatović S, Hey-Hawkins E. Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines. in Dalton Transactions. 2017;.
doi:10.1039/C7DT02027A .

Gozzi, Marta, Schwarze, Benedikt, Sárosi, Menyhárt-Botond, Lönnecke, Peter, Drača, Dijana, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Hey-Hawkins, Evamarie, "Antiproliferative activity of (η 6 -arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines" in Dalton Transactions (2017),
https://doi.org/10.1039/C7DT02027A . .