TY  - JOUR
AU  - Međedović, Milica
AU  - Mijatović, Aleksandar
AU  - Baošić, Rada
AU  - Lazić, Dejan
AU  - Milanović, Žiko
AU  - Marković, Zoran
AU  - Milovanović, Jelena
AU  - Arsenijević, Dragana
AU  - Stojanović, Bojana
AU  - Arsenijević, Miloš
AU  - Milovanović, Marija
AU  - Petrović, Biljana
AU  - Rilak Simović, Ana
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6353
AB  - In order to discover new anticancer drugs, novel ruthenium(III) complexes [Ru(L)Cl(H2O)], where L is tetradentate Schiff base bis(acetylacetone)ethylendiimine (acacen, 1), bis(benzoylacetone)ethylendiimine (bzacen, 2), (acetylacetone)(benzoylaceton)ethylendiimine (acacbzacen, 3), bis(acetylacetone)propylendiimine (acacpn, 4), bis(benzoylacetone)propylendiimine (bzacpn, 5) or (acetylacetone)(benzoylaceton)propylendiimine (acacbzacpn, 6), were synthesized. The complexes 1 – 6 were characterized by elemental analysis, molar conductometry, and by various spectroscopic techniques, such as UV–Vis, IR, EPR, and ESI-MS. Based on in vitro DNA/BSA experiments, complexes 2 (bzacen) and 5 (bzacpn) with two aromatic rings showed the highest DNA/BSA-activity, suggesting that the presence of the aromatic ring on the tetradentate Schiff base ligand contributes to increased activity. Moreover, these two compounds showed the highest cytotoxic effects toward human, A549 and murine LLC1 lung cancer cells. These complexes altered the ratio of anti- and pro-apoptotic molecules and induced apoptosis of A549 cells. Further, complexes 2 and 5 reduced the percentage of Mcl1 and Bcl2 expressing LLC1 cells, induced their apoptotic death and exerted an antiproliferative effect against LLC1. Finally, complex 5 reduced the volume of mouse primary heterotopic Lewis lung cancer, while complex 2 reduced the incidence and mean number of metastases per lung. Additionally, molecular docking with DNA revealed that the reduced number of aromatic rings or their absence causes lower intercalative properties of the complexes in order: 2 > 5 > 6 > 3 > 4 > 1. It was observed that conventional hydrogen bonds and hydrophobic interactions contribute to the stabilization of the structures of complex-DNA. A molecular docking study with BSA revealed a predominance of 1 – 6 in binding affinity to the active site III, a third D-shaped hydrophobic pocket within subdomain IB.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes
VL  - 248
SP  - 112363
DO  - 10.1016/j.jinorgbio.2023.112363
ER  - 

@article{
author = "Međedović, Milica and Mijatović, Aleksandar and Baošić, Rada and Lazić, Dejan and Milanović, Žiko and Marković, Zoran and Milovanović, Jelena and Arsenijević, Dragana and Stojanović, Bojana and Arsenijević, Miloš and Milovanović, Marija and Petrović, Biljana and Rilak Simović, Ana",
year = "2023",
abstract = "In order to discover new anticancer drugs, novel ruthenium(III) complexes [Ru(L)Cl(H2O)], where L is tetradentate Schiff base bis(acetylacetone)ethylendiimine (acacen, 1), bis(benzoylacetone)ethylendiimine (bzacen, 2), (acetylacetone)(benzoylaceton)ethylendiimine (acacbzacen, 3), bis(acetylacetone)propylendiimine (acacpn, 4), bis(benzoylacetone)propylendiimine (bzacpn, 5) or (acetylacetone)(benzoylaceton)propylendiimine (acacbzacpn, 6), were synthesized. The complexes 1 – 6 were characterized by elemental analysis, molar conductometry, and by various spectroscopic techniques, such as UV–Vis, IR, EPR, and ESI-MS. Based on in vitro DNA/BSA experiments, complexes 2 (bzacen) and 5 (bzacpn) with two aromatic rings showed the highest DNA/BSA-activity, suggesting that the presence of the aromatic ring on the tetradentate Schiff base ligand contributes to increased activity. Moreover, these two compounds showed the highest cytotoxic effects toward human, A549 and murine LLC1 lung cancer cells. These complexes altered the ratio of anti- and pro-apoptotic molecules and induced apoptosis of A549 cells. Further, complexes 2 and 5 reduced the percentage of Mcl1 and Bcl2 expressing LLC1 cells, induced their apoptotic death and exerted an antiproliferative effect against LLC1. Finally, complex 5 reduced the volume of mouse primary heterotopic Lewis lung cancer, while complex 2 reduced the incidence and mean number of metastases per lung. Additionally, molecular docking with DNA revealed that the reduced number of aromatic rings or their absence causes lower intercalative properties of the complexes in order: 2 > 5 > 6 > 3 > 4 > 1. It was observed that conventional hydrogen bonds and hydrophobic interactions contribute to the stabilization of the structures of complex-DNA. A molecular docking study with BSA revealed a predominance of 1 – 6 in binding affinity to the active site III, a third D-shaped hydrophobic pocket within subdomain IB.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes",
volume = "248",
pages = "112363",
doi = "10.1016/j.jinorgbio.2023.112363"
}

Međedović, M., Mijatović, A., Baošić, R., Lazić, D., Milanović, Ž., Marković, Z., Milovanović, J., Arsenijević, D., Stojanović, B., Arsenijević, M., Milovanović, M., Petrović, B.,& Rilak Simović, A.. (2023). Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes. in Journal of Inorganic Biochemistry
Elsevier., 248, 112363.
https://doi.org/10.1016/j.jinorgbio.2023.112363

Međedović M, Mijatović A, Baošić R, Lazić D, Milanović Ž, Marković Z, Milovanović J, Arsenijević D, Stojanović B, Arsenijević M, Milovanović M, Petrović B, Rilak Simović A. Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes. in Journal of Inorganic Biochemistry. 2023;248:112363.
doi:10.1016/j.jinorgbio.2023.112363 .

Međedović, Milica, Mijatović, Aleksandar, Baošić, Rada, Lazić, Dejan, Milanović, Žiko, Marković, Zoran, Milovanović, Jelena, Arsenijević, Dragana, Stojanović, Bojana, Arsenijević, Miloš, Milovanović, Marija, Petrović, Biljana, Rilak Simović, Ana, "Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes" in Journal of Inorganic Biochemistry, 248 (2023):112363,
https://doi.org/10.1016/j.jinorgbio.2023.112363 . .

TY  - JOUR
AU  - Đorđević, Dragana S.
AU  - Milovanović, Jelena
AU  - Jurisević, Milena
AU  - Stojanović, Bojana
AU  - Cvetković, Olga
AU  - Pergal, Marija V.
AU  - Ristanović, Elizabeta
AU  - Vojvodić, Danilo
AU  - Simić, Miloš
AU  - Manojlović, Dragan D.
AU  - Milovanović, Marija
AU  - Arsenijević, Nebojša
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3858
AB  - Copper serves as a limiting factor for multiple steps of tumour progression, including angiogenesis, growth and metastasis. High levels of copper have been found in a wide spectrum of human cancers. Antitumour activities of copper-chelating drugs have been reported in animal models. Organosulfur compounds (diallyl sulfide, DAS; diallyl disulfide, DADS; S-ethylcysteine, SEC; N-acetylcysteine, NAC) derived from garlic exhibit marked copper-chelating activity. We analysed a mixture of fifteen n-propyl polysulfides (DPPS) for potential antitumour activity against several murine tumour cell lines, including colon carcinoma (CT26), mammary carcinoma (4T1) and melanoma cell lines (B16F10), and compared the effects with the antiproliferative effect in highly proliferative murine mesenchymal stem cells (mMSCs). The effects of the mixture of n-propyl polysulfides (100%) on cell viability were determined using MTT assays. Cell apoptosis was analysed using Annexin V-FITC/PI assays.

The results of the MTT assays indicate that this standardized mixture of n-propyl polysulfides has a strong, dose-dependent cytotoxic effect against all three of the tested tumour cell lines (CT26, 4T1, B16F10). The cytotoxic effect of the n-propyl polysulfide mixture against the CT26 and B16F10 cell lines was much stronger than that of cisplatin and was significantly weaker in mMSCs, which are non-cancerous and highly proliferative cells, than in cancer cells. Flow cytometric analysis of CT26 and 4T1 cells revealed that apoptosis was not the dominant mechanism of cell death induced by the n-propyl polysulfide mixture. The n-propyl polysulfide mixture exerted highly cytotoxic activity against murine colon carcinoma and melanoma cell lines, but its antiproliferative activity against mMSCs was significantly lower than that of cisplatin.
T2  - Serbian Journal of Experimental and Clinical Research
T1  - Antitumour effect of a mixture of n-propyl polysulfides In vitro
VL  - 20
IS  - 4
SP  - 295
EP  - 300
DO  - 10.1515/sjecr-2017-0069
ER  - 

@article{
author = "Đorđević, Dragana S. and Milovanović, Jelena and Jurisević, Milena and Stojanović, Bojana and Cvetković, Olga and Pergal, Marija V. and Ristanović, Elizabeta and Vojvodić, Danilo and Simić, Miloš and Manojlović, Dragan D. and Milovanović, Marija and Arsenijević, Nebojša",
year = "2019",
abstract = "Copper serves as a limiting factor for multiple steps of tumour progression, including angiogenesis, growth and metastasis. High levels of copper have been found in a wide spectrum of human cancers. Antitumour activities of copper-chelating drugs have been reported in animal models. Organosulfur compounds (diallyl sulfide, DAS; diallyl disulfide, DADS; S-ethylcysteine, SEC; N-acetylcysteine, NAC) derived from garlic exhibit marked copper-chelating activity. We analysed a mixture of fifteen n-propyl polysulfides (DPPS) for potential antitumour activity against several murine tumour cell lines, including colon carcinoma (CT26), mammary carcinoma (4T1) and melanoma cell lines (B16F10), and compared the effects with the antiproliferative effect in highly proliferative murine mesenchymal stem cells (mMSCs). The effects of the mixture of n-propyl polysulfides (100%) on cell viability were determined using MTT assays. Cell apoptosis was analysed using Annexin V-FITC/PI assays.

The results of the MTT assays indicate that this standardized mixture of n-propyl polysulfides has a strong, dose-dependent cytotoxic effect against all three of the tested tumour cell lines (CT26, 4T1, B16F10). The cytotoxic effect of the n-propyl polysulfide mixture against the CT26 and B16F10 cell lines was much stronger than that of cisplatin and was significantly weaker in mMSCs, which are non-cancerous and highly proliferative cells, than in cancer cells. Flow cytometric analysis of CT26 and 4T1 cells revealed that apoptosis was not the dominant mechanism of cell death induced by the n-propyl polysulfide mixture. The n-propyl polysulfide mixture exerted highly cytotoxic activity against murine colon carcinoma and melanoma cell lines, but its antiproliferative activity against mMSCs was significantly lower than that of cisplatin.",
journal = "Serbian Journal of Experimental and Clinical Research",
title = "Antitumour effect of a mixture of n-propyl polysulfides In vitro",
volume = "20",
number = "4",
pages = "295-300",
doi = "10.1515/sjecr-2017-0069"
}

Đorđević, D. S., Milovanović, J., Jurisević, M., Stojanović, B., Cvetković, O., Pergal, M. V., Ristanović, E., Vojvodić, D., Simić, M., Manojlović, D. D., Milovanović, M.,& Arsenijević, N.. (2019). Antitumour effect of a mixture of n-propyl polysulfides In vitro. in Serbian Journal of Experimental and Clinical Research, 20(4), 295-300.
https://doi.org/10.1515/sjecr-2017-0069

Đorđević DS, Milovanović J, Jurisević M, Stojanović B, Cvetković O, Pergal MV, Ristanović E, Vojvodić D, Simić M, Manojlović DD, Milovanović M, Arsenijević N. Antitumour effect of a mixture of n-propyl polysulfides In vitro. in Serbian Journal of Experimental and Clinical Research. 2019;20(4):295-300.
doi:10.1515/sjecr-2017-0069 .

Đorđević, Dragana S., Milovanović, Jelena, Jurisević, Milena, Stojanović, Bojana, Cvetković, Olga, Pergal, Marija V., Ristanović, Elizabeta, Vojvodić, Danilo, Simić, Miloš, Manojlović, Dragan D., Milovanović, Marija, Arsenijević, Nebojša, "Antitumour effect of a mixture of n-propyl polysulfides In vitro" in Serbian Journal of Experimental and Clinical Research, 20, no. 4 (2019):295-300,
https://doi.org/10.1515/sjecr-2017-0069 . .

TY  - JOUR
AU  - Jurišević, Milena
AU  - Radosavljević, Gordana
AU  - Arsenijević, Aleksandar
AU  - Milovanović, Marija
AU  - Gajović, Nevena
AU  - Đorđević, Dragana S.
AU  - Milovanović, Jelena
AU  - Stojanović, Bojana
AU  - Ilić, Aleksandar
AU  - Sabo, Tibor
AU  - Kanjevac, Tatjana
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/216
AB  - e design of platinum based drugs is not a new field of interest. Platinum complexes are widely used as anticancer agents and currently, approximately 30 platinum(II) and platinum(IV) entered into some of the phases of clinical trials. A special place in today’s research belongs to platinum complexes with diammine ligands. A large number of edda (ethylenediamine- N, N’-diacetate)-type ligands and their corresponding metal complexes has been successfully synthesized. is article summarizes recent progress in research on edda-type-platinum complexes. Some of these agents achieves better effect compared to the gold standard (cisplatin). It has been shown that there is a possible relationship between the length of the ligand ester group carbon chain and its cytotoxic effect. In most cases the longer the ester chain is the greater is the antitumor activity. Of particular interest are the noticeable effects of some new platinum compound with edda-type ligand on cell lines that are known to have a high level of cisplatin-resistance. Exanimate complexes appear to have a diff erent mode of mechanism of action compared with cisplatin which includes apoptotic and necrotic cell death. ere are indications that further investigations of these compounds may be very useful in overcoming the problems associated global cancer statistic. © 2016, University of Kragujevac, Faculty of Science. All rights reserved.
AB  - Kompleski platine koriste se kao osnova za dizajn novih lekova. Oni su u širokoj upotrebi kao antitumorski agensi i do danas je oko 30 komplesa platine(II) i platine(IV) u nekoj od faza kliničkog ispitivanja. Posebno mesto u današnjim istaživanjima zauzimaju kompleksi metala sa edda ligandima. Uspešno je sintetisan veliki broj novih edda liganda i odgovarajućih kompleksa. Neki od ovih agensa pokazuju bolju aktivnost od zlatnog standarda, cisplatine. Pokazano je da postoji moguća veza između dužine ugljovodiničnog lanca estraske grupe liganda i citotoksičnog efekta. U većini slučajeva dužina lanca direktno korelira sa antitumorskom aktivnošću. Zabeležena je efikasnija citotoksicna aktivnost određenih kompleska platine sa edda ligandima na ćelijskim linijama tumora koji pokazuju odgovarajući stepen rezistencije na cisplatinu. Ispitivani komleksi imaju različit mehanizam dejstva od cisplatine, koji uključuje elemente nekrotične i programirane ćelijske smrti. Postoje nagoveštaji da dalja istraživanja ovih agensa mogu biti značajna za prevazilaženje globalnog problema sa kojim se svet danas suočava, a koji se odnosi na stalni porast osoba obolelih od karcinoma.
T2  - Serbian Journal of Experimental and Clinical Research (ranije: Medicus)
T1  - Platinum complexes with edda ethylenediamine n, n diacetate ligands as potential anticancer agents [Kompleksi platine sa edda etilendiamin N, N’ diacetat ligandima kao potencijalni antitumorski agensi]
T1  - Kompleksi platine sa edda (etilendiamin-N, N'-diacetat) ligandima kao potencijalni antitumorski agensi
VL  - 17
IS  - 4
SP  - 285
EP  - 295
DO  - 10.1515/SJECR-2016-0042
ER  - 

@article{
author = "Jurišević, Milena and Radosavljević, Gordana and Arsenijević, Aleksandar and Milovanović, Marija and Gajović, Nevena and Đorđević, Dragana S. and Milovanović, Jelena and Stojanović, Bojana and Ilić, Aleksandar and Sabo, Tibor and Kanjevac, Tatjana",
year = "2016",
abstract = "e design of platinum based drugs is not a new field of interest. Platinum complexes are widely used as anticancer agents and currently, approximately 30 platinum(II) and platinum(IV) entered into some of the phases of clinical trials. A special place in today’s research belongs to platinum complexes with diammine ligands. A large number of edda (ethylenediamine- N, N’-diacetate)-type ligands and their corresponding metal complexes has been successfully synthesized. is article summarizes recent progress in research on edda-type-platinum complexes. Some of these agents achieves better effect compared to the gold standard (cisplatin). It has been shown that there is a possible relationship between the length of the ligand ester group carbon chain and its cytotoxic effect. In most cases the longer the ester chain is the greater is the antitumor activity. Of particular interest are the noticeable effects of some new platinum compound with edda-type ligand on cell lines that are known to have a high level of cisplatin-resistance. Exanimate complexes appear to have a diff erent mode of mechanism of action compared with cisplatin which includes apoptotic and necrotic cell death. ere are indications that further investigations of these compounds may be very useful in overcoming the problems associated global cancer statistic. © 2016, University of Kragujevac, Faculty of Science. All rights reserved., Kompleski platine koriste se kao osnova za dizajn novih lekova. Oni su u širokoj upotrebi kao antitumorski agensi i do danas je oko 30 komplesa platine(II) i platine(IV) u nekoj od faza kliničkog ispitivanja. Posebno mesto u današnjim istaživanjima zauzimaju kompleksi metala sa edda ligandima. Uspešno je sintetisan veliki broj novih edda liganda i odgovarajućih kompleksa. Neki od ovih agensa pokazuju bolju aktivnost od zlatnog standarda, cisplatine. Pokazano je da postoji moguća veza između dužine ugljovodiničnog lanca estraske grupe liganda i citotoksičnog efekta. U većini slučajeva dužina lanca direktno korelira sa antitumorskom aktivnošću. Zabeležena je efikasnija citotoksicna aktivnost određenih kompleska platine sa edda ligandima na ćelijskim linijama tumora koji pokazuju odgovarajući stepen rezistencije na cisplatinu. Ispitivani komleksi imaju različit mehanizam dejstva od cisplatine, koji uključuje elemente nekrotične i programirane ćelijske smrti. Postoje nagoveštaji da dalja istraživanja ovih agensa mogu biti značajna za prevazilaženje globalnog problema sa kojim se svet danas suočava, a koji se odnosi na stalni porast osoba obolelih od karcinoma.",
journal = "Serbian Journal of Experimental and Clinical Research (ranije: Medicus)",
title = "Platinum complexes with edda ethylenediamine n, n diacetate ligands as potential anticancer agents [Kompleksi platine sa edda etilendiamin N, N’ diacetat ligandima kao potencijalni antitumorski agensi], Kompleksi platine sa edda (etilendiamin-N, N'-diacetat) ligandima kao potencijalni antitumorski agensi",
volume = "17",
number = "4",
pages = "285-295",
doi = "10.1515/SJECR-2016-0042"
}

Jurišević, M., Radosavljević, G., Arsenijević, A., Milovanović, M., Gajović, N., Đorđević, D. S., Milovanović, J., Stojanović, B., Ilić, A., Sabo, T.,& Kanjevac, T.. (2016). Platinum complexes with edda ethylenediamine n, n diacetate ligands as potential anticancer agents [Kompleksi platine sa edda etilendiamin N, N’ diacetat ligandima kao potencijalni antitumorski agensi]. in Serbian Journal of Experimental and Clinical Research (ranije: Medicus), 17(4), 285-295.
https://doi.org/10.1515/SJECR-2016-0042

Jurišević M, Radosavljević G, Arsenijević A, Milovanović M, Gajović N, Đorđević DS, Milovanović J, Stojanović B, Ilić A, Sabo T, Kanjevac T. Platinum complexes with edda ethylenediamine n, n diacetate ligands as potential anticancer agents [Kompleksi platine sa edda etilendiamin N, N’ diacetat ligandima kao potencijalni antitumorski agensi]. in Serbian Journal of Experimental and Clinical Research (ranije: Medicus). 2016;17(4):285-295.
doi:10.1515/SJECR-2016-0042 .

Jurišević, Milena, Radosavljević, Gordana, Arsenijević, Aleksandar, Milovanović, Marija, Gajović, Nevena, Đorđević, Dragana S., Milovanović, Jelena, Stojanović, Bojana, Ilić, Aleksandar, Sabo, Tibor, Kanjevac, Tatjana, "Platinum complexes with edda ethylenediamine n, n diacetate ligands as potential anticancer agents [Kompleksi platine sa edda etilendiamin N, N’ diacetat ligandima kao potencijalni antitumorski agensi]" in Serbian Journal of Experimental and Clinical Research (ranije: Medicus), 17, no. 4 (2016):285-295,
https://doi.org/10.1515/SJECR-2016-0042 . .