TY  - JOUR
AU  - Krunić, Matija
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Tovilović-Kovačević, Gordana
AU  - Zagović, Nevena
AU  - Mirčić, Aleksandar
AU  - Marković, Zoran
AU  - Todorović Marković, Biljana
AU  - Jovanović, Svetlana
AU  - Kleut, Duška
AU  - Mojović, Miloš
AU  - Nakarada, Đura
AU  - Marković, Olivera S.
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2021
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5467
AB  - We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuro blastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). 
GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent 
apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers 
displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of 
GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (
•
OH), superoxide 
anion (O2
•− ), and lipid peroxidation. Nonselective antioxidants, •
OH scavenging, and iron chelators, but not 
superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •
OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal 
protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective 
effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proauto phagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The 
antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and 
dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early 
(wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of 
GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •
OH/NO 
scavenging and induction of cytoprotective autophagy.
PB  - Elsevier
T2  - Free Radical Biology and Medicine
T1  - Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death
VL  - 177
SP  - 167
EP  - 180
DO  - 10.1016/j.freeradbiomed.2021.10.025
ER  - 

@article{
author = "Krunić, Matija and Ristić, Biljana and Bošnjak, Mihajlo and Paunović, Verica and Tovilović-Kovačević, Gordana and Zagović, Nevena and Mirčić, Aleksandar and Marković, Zoran and Todorović Marković, Biljana and Jovanović, Svetlana and Kleut, Duška and Mojović, Miloš and Nakarada, Đura and Marković, Olivera S. and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2021",
abstract = "We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuro blastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). 
GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent 
apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers 
displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of 
GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (
•
OH), superoxide 
anion (O2
•− ), and lipid peroxidation. Nonselective antioxidants, •
OH scavenging, and iron chelators, but not 
superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •
OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal 
protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective 
effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proauto phagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The 
antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and 
dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early 
(wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of 
GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •
OH/NO 
scavenging and induction of cytoprotective autophagy.",
publisher = "Elsevier",
journal = "Free Radical Biology and Medicine",
title = "Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death",
volume = "177",
pages = "167-180",
doi = "10.1016/j.freeradbiomed.2021.10.025"
}

Krunić, M., Ristić, B., Bošnjak, M., Paunović, V., Tovilović-Kovačević, G., Zagović, N., Mirčić, A., Marković, Z., Todorović Marković, B., Jovanović, S., Kleut, D., Mojović, M., Nakarada, Đ., Marković, O. S., Vuković, I., Harhaji-Trajković, L.,& Trajković, V.. (2021). Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death. in Free Radical Biology and Medicine
Elsevier., 177, 167-180.
https://doi.org/10.1016/j.freeradbiomed.2021.10.025

Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zagović N, Mirčić A, Marković Z, Todorović Marković B, Jovanović S, Kleut D, Mojović M, Nakarada Đ, Marković OS, Vuković I, Harhaji-Trajković L, Trajković V. Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death. in Free Radical Biology and Medicine. 2021;177:167-180.
doi:10.1016/j.freeradbiomed.2021.10.025 .

Krunić, Matija, Ristić, Biljana, Bošnjak, Mihajlo, Paunović, Verica, Tovilović-Kovačević, Gordana, Zagović, Nevena, Mirčić, Aleksandar, Marković, Zoran, Todorović Marković, Biljana, Jovanović, Svetlana, Kleut, Duška, Mojović, Miloš, Nakarada, Đura, Marković, Olivera S., Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death" in Free Radical Biology and Medicine, 177 (2021):167-180,
https://doi.org/10.1016/j.freeradbiomed.2021.10.025 . .

TY  - JOUR
AU  - Misirlić-Denčić, Sonja
AU  - Poljarević, Jelena
AU  - Isaković, Anđelka M.
AU  - Sabo, Tibor
AU  - Marković, Ivanka
AU  - Trajković, Vladimir S.
PY  - 2020
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5072
AB  - Background: The discovery of cisplatin and the subsequent research revealed the importance of dinitrogen-containing moiety for the anticancer action of metal complexes. Moreover, certain diamine ligands alone display cytotoxicity that contributes to the overall activity of corresponding complexes.

Objective: To summarize the current knowledge on the anticancer efficacy, selectivity, and the mechanisms of action of metal complexes with various types of diamine ligands.

Methods: The contribution of aliphatic acyclic, aliphatic cyclic, and aromatic diamine ligands to the anticancer activity and selectivity/toxicity of metal complexes with different metal ions were analyzed by comparison with organic ligand alone and/or conventional platinum-based chemotherapeutics.

Results: The aliphatic acyclic diamine ligands are present mostly in complexes with platinum. Aliphatic cyclic diamines are part of Pt(II), Ru(II) and Au(III) complexes, while aromatic diamine ligands are found in Pt(II), Ru(II), Pd(II) and Ir(III) complexes. The type and oxidation state of metal ions greatly influences the cytotoxicity of metal complexes with aliphatic acyclic diamine ligands. Lipophilicity of organic ligands, dependent on alkyl-side chain length and structure, determines their cellular uptake, with edda and eddp/eddip ligands being most useful in this regard. Aliphatic cyclic diamine ligands improved the activity/toxicity ratio of oxaliplatin-type complexes. The complexes with aromatic diamine ligands remain unexplored regarding their anticancer mechanism. The investigated complexes mainly caused apoptotic or necrotic cell death.

Conclusion: Metal complexes with diamine ligands are promising candidates for efficient and more selective alternatives to conventional platinum-based chemotherapeutics. Further research is required to reveal the chemico-physical properties and molecular mechanisms underlying their biological activity.
PB  - Bentham Science
T2  - Current Medicinal Chemistry
T1  - Current development of metal complexes with diamine ligands as potential anticancer agents
VL  - 27
IS  - 3
SP  - 380
EP  - 410
DO  - 10.2174/0929867325666181031114306
ER  - 

@article{
author = "Misirlić-Denčić, Sonja and Poljarević, Jelena and Isaković, Anđelka M. and Sabo, Tibor and Marković, Ivanka and Trajković, Vladimir S.",
year = "2020",
abstract = "Background: The discovery of cisplatin and the subsequent research revealed the importance of dinitrogen-containing moiety for the anticancer action of metal complexes. Moreover, certain diamine ligands alone display cytotoxicity that contributes to the overall activity of corresponding complexes.

Objective: To summarize the current knowledge on the anticancer efficacy, selectivity, and the mechanisms of action of metal complexes with various types of diamine ligands.

Methods: The contribution of aliphatic acyclic, aliphatic cyclic, and aromatic diamine ligands to the anticancer activity and selectivity/toxicity of metal complexes with different metal ions were analyzed by comparison with organic ligand alone and/or conventional platinum-based chemotherapeutics.

Results: The aliphatic acyclic diamine ligands are present mostly in complexes with platinum. Aliphatic cyclic diamines are part of Pt(II), Ru(II) and Au(III) complexes, while aromatic diamine ligands are found in Pt(II), Ru(II), Pd(II) and Ir(III) complexes. The type and oxidation state of metal ions greatly influences the cytotoxicity of metal complexes with aliphatic acyclic diamine ligands. Lipophilicity of organic ligands, dependent on alkyl-side chain length and structure, determines their cellular uptake, with edda and eddp/eddip ligands being most useful in this regard. Aliphatic cyclic diamine ligands improved the activity/toxicity ratio of oxaliplatin-type complexes. The complexes with aromatic diamine ligands remain unexplored regarding their anticancer mechanism. The investigated complexes mainly caused apoptotic or necrotic cell death.

Conclusion: Metal complexes with diamine ligands are promising candidates for efficient and more selective alternatives to conventional platinum-based chemotherapeutics. Further research is required to reveal the chemico-physical properties and molecular mechanisms underlying their biological activity.",
publisher = "Bentham Science",
journal = "Current Medicinal Chemistry",
title = "Current development of metal complexes with diamine ligands as potential anticancer agents",
volume = "27",
number = "3",
pages = "380-410",
doi = "10.2174/0929867325666181031114306"
}

Misirlić-Denčić, S., Poljarević, J., Isaković, A. M., Sabo, T., Marković, I.,& Trajković, V. S.. (2020). Current development of metal complexes with diamine ligands as potential anticancer agents. in Current Medicinal Chemistry
Bentham Science., 27(3), 380-410.
https://doi.org/10.2174/0929867325666181031114306

Misirlić-Denčić S, Poljarević J, Isaković AM, Sabo T, Marković I, Trajković VS. Current development of metal complexes with diamine ligands as potential anticancer agents. in Current Medicinal Chemistry. 2020;27(3):380-410.
doi:10.2174/0929867325666181031114306 .

Misirlić-Denčić, Sonja, Poljarević, Jelena, Isaković, Anđelka M., Sabo, Tibor, Marković, Ivanka, Trajković, Vladimir S., "Current development of metal complexes with diamine ligands as potential anticancer agents" in Current Medicinal Chemistry, 27, no. 3 (2020):380-410,
https://doi.org/10.2174/0929867325666181031114306 . .

TY  - JOUR
AU  - Isaković, Anđelka M.
AU  - Petričević, Saša
AU  - Ristić, Slavica M.
AU  - Popadić, Dušan
AU  - Kravić-Stevović, Tamara
AU  - Zogović, Nevena
AU  - Poljarević, Jelena
AU  - Živanović-Radnić, Tatjana
AU  - Sabo, Tibor
AU  - Isaković, Aleksandra J.
AU  - Marković, Ivanka
AU  - Trajković, Vladimir S.
AU  - Misirlić-Denčić, Sonja
PY  - 2018
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2086
AB  - Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O, O-diethyl-(S, S)-ethylenediamineN, N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspasedependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Melanoma Research
T1  - In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid
VL  - 28
IS  - 1
SP  - 8
EP  - 20
DO  - 10.1097/CMR.0000000000000409
ER  - 

@article{
author = "Isaković, Anđelka M. and Petričević, Saša and Ristić, Slavica M. and Popadić, Dušan and Kravić-Stevović, Tamara and Zogović, Nevena and Poljarević, Jelena and Živanović-Radnić, Tatjana and Sabo, Tibor and Isaković, Aleksandra J. and Marković, Ivanka and Trajković, Vladimir S. and Misirlić-Denčić, Sonja",
year = "2018",
abstract = "Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O, O-diethyl-(S, S)-ethylenediamineN, N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspasedependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Melanoma Research",
title = "In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid",
volume = "28",
number = "1",
pages = "8-20",
doi = "10.1097/CMR.0000000000000409"
}

Isaković, A. M., Petričević, S., Ristić, S. M., Popadić, D., Kravić-Stevović, T., Zogović, N., Poljarević, J., Živanović-Radnić, T., Sabo, T., Isaković, A. J., Marković, I., Trajković, V. S.,& Misirlić-Denčić, S.. (2018). In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid. in Melanoma Research
Lippincott Williams & Wilkins, Philadelphia., 28(1), 8-20.
https://doi.org/10.1097/CMR.0000000000000409

Isaković AM, Petričević S, Ristić SM, Popadić D, Kravić-Stevović T, Zogović N, Poljarević J, Živanović-Radnić T, Sabo T, Isaković AJ, Marković I, Trajković VS, Misirlić-Denčić S. In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid. in Melanoma Research. 2018;28(1):8-20.
doi:10.1097/CMR.0000000000000409 .

Isaković, Anđelka M., Petričević, Saša, Ristić, Slavica M., Popadić, Dušan, Kravić-Stevović, Tamara, Zogović, Nevena, Poljarević, Jelena, Živanović-Radnić, Tatjana, Sabo, Tibor, Isaković, Aleksandra J., Marković, Ivanka, Trajković, Vladimir S., Misirlić-Denčić, Sonja, "In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid" in Melanoma Research, 28, no. 1 (2018):8-20,
https://doi.org/10.1097/CMR.0000000000000409 . .

TY  - JOUR
AU  - Paunović, Verica
AU  - Kosic, Milica
AU  - Đorđević, S.
AU  - Žugić, Ana
AU  - Đalinac, Nataša
AU  - Gašić, Uroš M.
AU  - Trajković, Vladimir S.
AU  - Harhaji-Trajkovic, Ljubica
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2434
AB  - Marrubium vulgare is a European medicinal plant with numerous beneficial effects on human health. The aim of the study was to isolate the plant ethanolic extract (MVE) and to investigate its anti-melanoma and anti-glioma effects. MVE was prepared by the modified pharmacopoeial percolation method and characterized by UHPLC-LTQ OrbiTrap MS. MVE dose-dependently reduced viability of melanoma (B16) and glioma (U251) cells, but not peripheral blood mononuclear cells. It arrested cell cycle in S+G2/M phase, which was associated with the activation of MAP kinase p38 and up-regulation of antiproliferative genes p53, p21 and p27. MVE induced oxidative stress, while antioxidants abrogated its antitumor effect. Furthermore, MVE induced mitochondrial depolarization, activation of caspase-9 and -3, Parp cleavage, phosphatidylserine exposure and DNA fragmentation. The mitochondrial apoptotic pathway was associated with the up-regulation of proapoptotic genes Pten, Bak1, Apaf1, and Puma and down-regulation of antiapoptotic genes survivin and Xiap. MVE also stimulated the expression of autophagy-related genes Atg5, Atg7, Atg12, Beclin-1, Gabarab and Sqstm1, as well as LC3-I conversion to the autophagosome associated LC3-II, while autophagy inhibitors exacerbated its cytotoxicity. Finally, the most abundant phenolic components of MVE, ferulic, p-hydroxybenzoic, caffeic and chlorogenic acids, did not exert a profound effect on viability of tumor cells, suggesting that other components individually or in concert are the mediators of the extracts' cytotoxicity. By demonstrating the ability of MVE to inhibit proliferation, induce apoptosis and cytoprotective autophagy, our results suggest that MVE, alone or combined with autophagy inhibitors, could be a good candidate for anti-melanoma and anti-glioma therapy.
PB  - C M B  Assoc, Poitiers
T2  - Cellular and Molecular Biology
T1  - Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro
VL  - 62
IS  - 11
SP  - 108
EP  - 114
DO  - 10.14715/cmb/2016.62.11.18
ER  - 

@article{
author = "Paunović, Verica and Kosic, Milica and Đorđević, S. and Žugić, Ana and Đalinac, Nataša and Gašić, Uroš M. and Trajković, Vladimir S. and Harhaji-Trajkovic, Ljubica",
year = "2016",
abstract = "Marrubium vulgare is a European medicinal plant with numerous beneficial effects on human health. The aim of the study was to isolate the plant ethanolic extract (MVE) and to investigate its anti-melanoma and anti-glioma effects. MVE was prepared by the modified pharmacopoeial percolation method and characterized by UHPLC-LTQ OrbiTrap MS. MVE dose-dependently reduced viability of melanoma (B16) and glioma (U251) cells, but not peripheral blood mononuclear cells. It arrested cell cycle in S+G2/M phase, which was associated with the activation of MAP kinase p38 and up-regulation of antiproliferative genes p53, p21 and p27. MVE induced oxidative stress, while antioxidants abrogated its antitumor effect. Furthermore, MVE induced mitochondrial depolarization, activation of caspase-9 and -3, Parp cleavage, phosphatidylserine exposure and DNA fragmentation. The mitochondrial apoptotic pathway was associated with the up-regulation of proapoptotic genes Pten, Bak1, Apaf1, and Puma and down-regulation of antiapoptotic genes survivin and Xiap. MVE also stimulated the expression of autophagy-related genes Atg5, Atg7, Atg12, Beclin-1, Gabarab and Sqstm1, as well as LC3-I conversion to the autophagosome associated LC3-II, while autophagy inhibitors exacerbated its cytotoxicity. Finally, the most abundant phenolic components of MVE, ferulic, p-hydroxybenzoic, caffeic and chlorogenic acids, did not exert a profound effect on viability of tumor cells, suggesting that other components individually or in concert are the mediators of the extracts' cytotoxicity. By demonstrating the ability of MVE to inhibit proliferation, induce apoptosis and cytoprotective autophagy, our results suggest that MVE, alone or combined with autophagy inhibitors, could be a good candidate for anti-melanoma and anti-glioma therapy.",
publisher = "C M B  Assoc, Poitiers",
journal = "Cellular and Molecular Biology",
title = "Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro",
volume = "62",
number = "11",
pages = "108-114",
doi = "10.14715/cmb/2016.62.11.18"
}

Paunović, V., Kosic, M., Đorđević, S., Žugić, A., Đalinac, N., Gašić, U. M., Trajković, V. S.,& Harhaji-Trajkovic, L.. (2016). Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro. in Cellular and Molecular Biology
C M B  Assoc, Poitiers., 62(11), 108-114.
https://doi.org/10.14715/cmb/2016.62.11.18

Paunović V, Kosic M, Đorđević S, Žugić A, Đalinac N, Gašić UM, Trajković VS, Harhaji-Trajkovic L. Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro. in Cellular and Molecular Biology. 2016;62(11):108-114.
doi:10.14715/cmb/2016.62.11.18 .

Paunović, Verica, Kosic, Milica, Đorđević, S., Žugić, Ana, Đalinac, Nataša, Gašić, Uroš M., Trajković, Vladimir S., Harhaji-Trajkovic, Ljubica, "Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro" in Cellular and Molecular Biology, 62, no. 11 (2016):108-114,
https://doi.org/10.14715/cmb/2016.62.11.18 . .

TY  - JOUR
AU  - Trifunović, Snežana S.
AU  - Isaković, Anđelka M.
AU  - Isaković, Aleksandra J.
AU  - Vučković, Ivan M.
AU  - Mandić, Boris
AU  - Novaković, Miroslav M.
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan M.
AU  - Trajković, Vladimir S.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1511
AB  - Further phytochemical investigation of the aerial parts of Achillea clavennae has resulted in the isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and the iso-seco-guaianolide 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known compounds were also found, of which 9-acetoxycanin (5), sintenin (6), and oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were elucidated by combined spectroscopic methods (1D and 2DNMR, HRESIMS, CIMS, and FTIR). While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Planta Medica
T1  - Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae
VL  - 80
IS  - 4
SP  - 297
EP  - 305
DO  - 10.1055/s-0033-1360312
ER  - 

@article{
author = "Trifunović, Snežana S. and Isaković, Anđelka M. and Isaković, Aleksandra J. and Vučković, Ivan M. and Mandić, Boris and Novaković, Miroslav M. and Vajs, Vlatka and Milosavljević, Slobodan M. and Trajković, Vladimir S.",
year = "2014",
abstract = "Further phytochemical investigation of the aerial parts of Achillea clavennae has resulted in the isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and the iso-seco-guaianolide 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known compounds were also found, of which 9-acetoxycanin (5), sintenin (6), and oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were elucidated by combined spectroscopic methods (1D and 2DNMR, HRESIMS, CIMS, and FTIR). While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Planta Medica",
title = "Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae",
volume = "80",
number = "4",
pages = "297-305",
doi = "10.1055/s-0033-1360312"
}

Trifunović, S. S., Isaković, A. M., Isaković, A. J., Vučković, I. M., Mandić, B., Novaković, M. M., Vajs, V., Milosavljević, S. M.,& Trajković, V. S.. (2014). Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae. in Planta Medica
Georg Thieme Verlag Kg, Stuttgart., 80(4), 297-305.
https://doi.org/10.1055/s-0033-1360312

Trifunović SS, Isaković AM, Isaković AJ, Vučković IM, Mandić B, Novaković MM, Vajs V, Milosavljević SM, Trajković VS. Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae. in Planta Medica. 2014;80(4):297-305.
doi:10.1055/s-0033-1360312 .

Trifunović, Snežana S., Isaković, Anđelka M., Isaković, Aleksandra J., Vučković, Ivan M., Mandić, Boris, Novaković, Miroslav M., Vajs, Vlatka, Milosavljević, Slobodan M., Trajković, Vladimir S., "Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae" in Planta Medica, 80, no. 4 (2014):297-305,
https://doi.org/10.1055/s-0033-1360312 . .

TY  - JOUR
AU  - Trifunović, Snežana S.
AU  - Isaković, Anđelka M.
AU  - Isaković, Aleksandra J.
AU  - Vučković, Ivan M.
AU  - Mandić, Boris
AU  - Novaković, Miroslav M.
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan M.
AU  - Trajković, Vladimir S.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2816
AB  - Further phytochemical investigation into the aerial parts of Achillea clavennae has resulted in the 3 
isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and 4 
the iso-seco-guaianolide, 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known 5 
compounds were also found in this plant species, of which 9 α -acetoxycanin (5), sintenin (6) and 6 
oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were 7 
elucidated by combined spectroscopic methods (1D and 2D NMR, HRESIMS, CIMS, FTIR). 8 
While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-9 
seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone 10 
apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.
PB  - Georg Thieme Verlag
T2  - Planta medica
T1  - Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae
VL  - 80
IS  - 4
SP  - 275
EP  - 305
DO  - 10.1055/s-0033-1360312
ER  - 

@article{
author = "Trifunović, Snežana S. and Isaković, Anđelka M. and Isaković, Aleksandra J. and Vučković, Ivan M. and Mandić, Boris and Novaković, Miroslav M. and Vajs, Vlatka and Milosavljević, Slobodan M. and Trajković, Vladimir S.",
year = "2014",
abstract = "Further phytochemical investigation into the aerial parts of Achillea clavennae has resulted in the 3 
isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and 4 
the iso-seco-guaianolide, 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known 5 
compounds were also found in this plant species, of which 9 α -acetoxycanin (5), sintenin (6) and 6 
oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were 7 
elucidated by combined spectroscopic methods (1D and 2D NMR, HRESIMS, CIMS, FTIR). 8 
While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-9 
seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone 10 
apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.",
publisher = "Georg Thieme Verlag",
journal = "Planta medica",
title = "Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae",
volume = "80",
number = "4",
pages = "275-305",
doi = "10.1055/s-0033-1360312"
}

Trifunović, S. S., Isaković, A. M., Isaković, A. J., Vučković, I. M., Mandić, B., Novaković, M. M., Vajs, V., Milosavljević, S. M.,& Trajković, V. S.. (2014). Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae. in Planta medica
Georg Thieme Verlag., 80(4), 275-305.
https://doi.org/10.1055/s-0033-1360312

Trifunović SS, Isaković AM, Isaković AJ, Vučković IM, Mandić B, Novaković MM, Vajs V, Milosavljević SM, Trajković VS. Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae. in Planta medica. 2014;80(4):275-305.
doi:10.1055/s-0033-1360312 .

Trifunović, Snežana S., Isaković, Anđelka M., Isaković, Aleksandra J., Vučković, Ivan M., Mandić, Boris, Novaković, Miroslav M., Vajs, Vlatka, Milosavljević, Slobodan M., Trajković, Vladimir S., "Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae" in Planta medica, 80, no. 4 (2014):275-305,
https://doi.org/10.1055/s-0033-1360312 . .

TY  - DATA
AU  - Trmčić, Milena
AU  - Matović, Radomir
AU  - Tovilović, Gordana
AU  - Ristić, Biljana Z.
AU  - Trajković, Vladimir S.
AU  - Ferjančić, Zorana
AU  - Saičić, Radomir
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3673
PB  - Royal Soc Chemistry, Cambridge
T2  - Organic and Biomolecular Chemistry
T1  - Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3673
ER  - 

@misc{
author = "Trmčić, Milena and Matović, Radomir and Tovilović, Gordana and Ristić, Biljana Z. and Trajković, Vladimir S. and Ferjančić, Zorana and Saičić, Radomir",
year = "2012",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Organic and Biomolecular Chemistry",
title = "Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3673"
}

Trmčić, M., Matović, R., Tovilović, G., Ristić, B. Z., Trajković, V. S., Ferjančić, Z.,& Saičić, R.. (2012). Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f. in Organic and Biomolecular Chemistry
Royal Soc Chemistry, Cambridge..
https://hdl.handle.net/21.15107/rcub_cherry_3673

Trmčić M, Matović R, Tovilović G, Ristić BZ, Trajković VS, Ferjančić Z, Saičić R. Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f. in Organic and Biomolecular Chemistry. 2012;.
https://hdl.handle.net/21.15107/rcub_cherry_3673 .

Trmčić, Milena, Matović, Radomir, Tovilović, Gordana, Ristić, Biljana Z., Trajković, Vladimir S., Ferjančić, Zorana, Saičić, Radomir, "Supplementary data for article:Trmčić, M.; Matović, R. V.; Tovilović, G.; Ristic, B. Z.; Trajković, V. S.; Ferjančić, Z.; Saičić, R. A Novel C,D-Spirolactone Analogue of Paclitaxel: Autophagy Instead of Apoptosis as a Previously Unknown Mechanism of Cytotoxic Action for Taxoids. Organic and Biomolecular Chemistry 2012, 10 (25), 4933–4942. https://doi.org/10.1039/c2ob25514f" in Organic and Biomolecular Chemistry (2012),
https://hdl.handle.net/21.15107/rcub_cherry_3673 .

TY  - JOUR
AU  - Trmčić, Milena
AU  - Matović, Radomir
AU  - Tovilović, Gordana
AU  - Ristić, Biljana Z.
AU  - Trajković, Vladimir S.
AU  - Ferjančić, Zorana
AU  - Saičić, Radomir
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1304
AB  - The design, synthesis and biological evaluation of a novel C, D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.
PB  - Royal Soc Chemistry, Cambridge
T2  - Organic and Biomolecular Chemistry
T1  - A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids
VL  - 10
IS  - 25
SP  - 4933
EP  - 4942
DO  - 10.1039/c2ob25514f
ER  - 

@article{
author = "Trmčić, Milena and Matović, Radomir and Tovilović, Gordana and Ristić, Biljana Z. and Trajković, Vladimir S. and Ferjančić, Zorana and Saičić, Radomir",
year = "2012",
abstract = "The design, synthesis and biological evaluation of a novel C, D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Organic and Biomolecular Chemistry",
title = "A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids",
volume = "10",
number = "25",
pages = "4933-4942",
doi = "10.1039/c2ob25514f"
}

Trmčić, M., Matović, R., Tovilović, G., Ristić, B. Z., Trajković, V. S., Ferjančić, Z.,& Saičić, R.. (2012). A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids. in Organic and Biomolecular Chemistry
Royal Soc Chemistry, Cambridge., 10(25), 4933-4942.
https://doi.org/10.1039/c2ob25514f

Trmčić M, Matović R, Tovilović G, Ristić BZ, Trajković VS, Ferjančić Z, Saičić R. A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids. in Organic and Biomolecular Chemistry. 2012;10(25):4933-4942.
doi:10.1039/c2ob25514f .

Trmčić, Milena, Matović, Radomir, Tovilović, Gordana, Ristić, Biljana Z., Trajković, Vladimir S., Ferjančić, Zorana, Saičić, Radomir, "A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids" in Organic and Biomolecular Chemistry, 10, no. 25 (2012):4933-4942,
https://doi.org/10.1039/c2ob25514f . .

TY  - JOUR
AU  - Maksimovic-Ivanic, Danijela
AU  - Mijatovic, Sanja
AU  - Mirkov, Ivana
AU  - Stošić-Grujičić, Stanislava D.
AU  - Miljković, Đorđe
AU  - Sabo, Tibor
AU  - Trajković, Vladimir S.
AU  - Kaluđerović, Goran N.
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1551
AB  - Tetrachlorido(O,O'-dibutyl-ethylenediamine-N,N'-di-3-propionate)-platinum(IV) complex, [PtCl4(n-Bu(2)eddp)], was previously found to be effective against fibrosarcoma and glioma cell lines. Here we presented that [PtCl4(n-Bu(2)eddp)] strongly reduced the growth of B16 melanoma cells in vitro. Inhibition of cell viability was accompanied with induction of both necrotic and apoptotic cell death. In addition, [PtCl4(n-Bu(2)eddp)] concealed the expansion of tumors induced in syngeneic C57BI/6 mice without visible signs of nephrotoxicity.
PB  - Royal Soc Chemistry, Cambridge
T2  - Metallomics
T1  - Melanoma tumor inhibition by tetrachlorido(O,O '-dibutyl-ethylenediamine-N,N '-di-3-propionate)platinum(IV) complex: in vitro and in vivo investigations
VL  - 4
IS  - 11
SP  - 1155
EP  - 1159
DO  - 10.1039/c2mt20150j
ER  - 

@article{
author = "Maksimovic-Ivanic, Danijela and Mijatovic, Sanja and Mirkov, Ivana and Stošić-Grujičić, Stanislava D. and Miljković, Đorđe and Sabo, Tibor and Trajković, Vladimir S. and Kaluđerović, Goran N.",
year = "2012",
abstract = "Tetrachlorido(O,O'-dibutyl-ethylenediamine-N,N'-di-3-propionate)-platinum(IV) complex, [PtCl4(n-Bu(2)eddp)], was previously found to be effective against fibrosarcoma and glioma cell lines. Here we presented that [PtCl4(n-Bu(2)eddp)] strongly reduced the growth of B16 melanoma cells in vitro. Inhibition of cell viability was accompanied with induction of both necrotic and apoptotic cell death. In addition, [PtCl4(n-Bu(2)eddp)] concealed the expansion of tumors induced in syngeneic C57BI/6 mice without visible signs of nephrotoxicity.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Metallomics",
title = "Melanoma tumor inhibition by tetrachlorido(O,O '-dibutyl-ethylenediamine-N,N '-di-3-propionate)platinum(IV) complex: in vitro and in vivo investigations",
volume = "4",
number = "11",
pages = "1155-1159",
doi = "10.1039/c2mt20150j"
}

Maksimovic-Ivanic, D., Mijatovic, S., Mirkov, I., Stošić-Grujičić, S. D., Miljković, Đ., Sabo, T., Trajković, V. S.,& Kaluđerović, G. N.. (2012). Melanoma tumor inhibition by tetrachlorido(O,O '-dibutyl-ethylenediamine-N,N '-di-3-propionate)platinum(IV) complex: in vitro and in vivo investigations. in Metallomics
Royal Soc Chemistry, Cambridge., 4(11), 1155-1159.
https://doi.org/10.1039/c2mt20150j

Maksimovic-Ivanic D, Mijatovic S, Mirkov I, Stošić-Grujičić SD, Miljković Đ, Sabo T, Trajković VS, Kaluđerović GN. Melanoma tumor inhibition by tetrachlorido(O,O '-dibutyl-ethylenediamine-N,N '-di-3-propionate)platinum(IV) complex: in vitro and in vivo investigations. in Metallomics. 2012;4(11):1155-1159.
doi:10.1039/c2mt20150j .

Maksimovic-Ivanic, Danijela, Mijatovic, Sanja, Mirkov, Ivana, Stošić-Grujičić, Stanislava D., Miljković, Đorđe, Sabo, Tibor, Trajković, Vladimir S., Kaluđerović, Goran N., "Melanoma tumor inhibition by tetrachlorido(O,O '-dibutyl-ethylenediamine-N,N '-di-3-propionate)platinum(IV) complex: in vitro and in vivo investigations" in Metallomics, 4, no. 11 (2012):1155-1159,
https://doi.org/10.1039/c2mt20150j . .

TY  - JOUR
AU  - Misirlić-Denčić, Sonja
AU  - Poljarević, Jelena
AU  - Vilimanovich, Urosh
AU  - Bogdanović, Andrija
AU  - Isaković, Aleksandra J.
AU  - Kravić-Stevović, Tamara
AU  - Dulović, Marija
AU  - Zogović, Nevena
AU  - Isaković, Anđelka M.
AU  - Grgurić-Šipka, Sanja
AU  - Bumbasirevic, Vladimir
AU  - Sabo, Tibor
AU  - Trajković, Vladimir S.
AU  - Marković, Ivanka
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1279
AB  - We investigated the cytotoxicity of recently synthesized (S,S)-ethyleridiamine-N,N'-di-2-(3-cyclohexyl)propanoic acid esters toward human leukemic cell lines and healthy blood mononuclear cells. Cell viability was assessed by acid phosphatase assay, apoptosis, and differentiation were analyzed by flow cytometry and electron microscopy, while intracellular localization of apoptosis-inducing factor (AIF) was determined by immunoblotting. It was demonstrated that methyl, ethyl, and n-propyl esters were toxic to HL-60, REH, MOLT-4, KG-1, JVM-2, and K-562 leukemic cell lines, while the nonesterified parental compound and n-butyl ester were devoid of cytotoxic action. The ethyl ester exhibited the highest cytotoxic activity (IC50 10.7 mu M-45.4 mu M), which was comparable to that of the prototypical anticancer drug cisplatin. The observed cytotoxic effect in HL-60 cells was associated with an increase in superoxide production and mitochondrial membrane depolarization, leading to apoptotic cell death characterized by phosphatidylserine externalization and DNA fragmentation in the absence of autophagic response. DNA fragmentation preceded caspase activation and followed AIF translocation from mitochondria to nucleus, which was indicative of caspase-independent apoptotic cell death. HL-60 cells treated with subtoxic concentration of the compound displayed morphological signs of granulocytic differentiation (nuclear indentations and presence of cytoplasmic primary granules), as well as an increased expression of differentiation markers CD11b and CD15. The cyclohexyl analogues of ethylenediamine dipropanoic acid were also toxic to peripheral blood mononuclear cells of both healthy controls and leukemic patients, the latter being more sensitive. Our data demonstrate that the toxicity of the investigated cyclohexyl compounds against leukemic cell lines is mediated by caspase-independent apoptosis associated with oxidative stress, mitochondrial dysfunction, and AIF translocation.
PB  - Amer Chemical Soc, Washington
T2  - Chemical Research in Toxicology
T1  - Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells
VL  - 25
IS  - 4
SP  - 931
EP  - 939
DO  - 10.1021/tx3000329
ER  - 

@article{
author = "Misirlić-Denčić, Sonja and Poljarević, Jelena and Vilimanovich, Urosh and Bogdanović, Andrija and Isaković, Aleksandra J. and Kravić-Stevović, Tamara and Dulović, Marija and Zogović, Nevena and Isaković, Anđelka M. and Grgurić-Šipka, Sanja and Bumbasirevic, Vladimir and Sabo, Tibor and Trajković, Vladimir S. and Marković, Ivanka",
year = "2012",
abstract = "We investigated the cytotoxicity of recently synthesized (S,S)-ethyleridiamine-N,N'-di-2-(3-cyclohexyl)propanoic acid esters toward human leukemic cell lines and healthy blood mononuclear cells. Cell viability was assessed by acid phosphatase assay, apoptosis, and differentiation were analyzed by flow cytometry and electron microscopy, while intracellular localization of apoptosis-inducing factor (AIF) was determined by immunoblotting. It was demonstrated that methyl, ethyl, and n-propyl esters were toxic to HL-60, REH, MOLT-4, KG-1, JVM-2, and K-562 leukemic cell lines, while the nonesterified parental compound and n-butyl ester were devoid of cytotoxic action. The ethyl ester exhibited the highest cytotoxic activity (IC50 10.7 mu M-45.4 mu M), which was comparable to that of the prototypical anticancer drug cisplatin. The observed cytotoxic effect in HL-60 cells was associated with an increase in superoxide production and mitochondrial membrane depolarization, leading to apoptotic cell death characterized by phosphatidylserine externalization and DNA fragmentation in the absence of autophagic response. DNA fragmentation preceded caspase activation and followed AIF translocation from mitochondria to nucleus, which was indicative of caspase-independent apoptotic cell death. HL-60 cells treated with subtoxic concentration of the compound displayed morphological signs of granulocytic differentiation (nuclear indentations and presence of cytoplasmic primary granules), as well as an increased expression of differentiation markers CD11b and CD15. The cyclohexyl analogues of ethylenediamine dipropanoic acid were also toxic to peripheral blood mononuclear cells of both healthy controls and leukemic patients, the latter being more sensitive. Our data demonstrate that the toxicity of the investigated cyclohexyl compounds against leukemic cell lines is mediated by caspase-independent apoptosis associated with oxidative stress, mitochondrial dysfunction, and AIF translocation.",
publisher = "Amer Chemical Soc, Washington",
journal = "Chemical Research in Toxicology",
title = "Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells",
volume = "25",
number = "4",
pages = "931-939",
doi = "10.1021/tx3000329"
}

Misirlić-Denčić, S., Poljarević, J., Vilimanovich, U., Bogdanović, A., Isaković, A. J., Kravić-Stevović, T., Dulović, M., Zogović, N., Isaković, A. M., Grgurić-Šipka, S., Bumbasirevic, V., Sabo, T., Trajković, V. S.,& Marković, I.. (2012). Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells. in Chemical Research in Toxicology
Amer Chemical Soc, Washington., 25(4), 931-939.
https://doi.org/10.1021/tx3000329

Misirlić-Denčić S, Poljarević J, Vilimanovich U, Bogdanović A, Isaković AJ, Kravić-Stevović T, Dulović M, Zogović N, Isaković AM, Grgurić-Šipka S, Bumbasirevic V, Sabo T, Trajković VS, Marković I. Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells. in Chemical Research in Toxicology. 2012;25(4):931-939.
doi:10.1021/tx3000329 .

Misirlić-Denčić, Sonja, Poljarević, Jelena, Vilimanovich, Urosh, Bogdanović, Andrija, Isaković, Aleksandra J., Kravić-Stevović, Tamara, Dulović, Marija, Zogović, Nevena, Isaković, Anđelka M., Grgurić-Šipka, Sanja, Bumbasirevic, Vladimir, Sabo, Tibor, Trajković, Vladimir S., Marković, Ivanka, "Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells" in Chemical Research in Toxicology, 25, no. 4 (2012):931-939,
https://doi.org/10.1021/tx3000329 . .

TY  - JOUR
AU  - Savić, Aleksandar
AU  - Dulović, Marija
AU  - Poljarević, Jelena
AU  - Misirlić-Denčić, Sonja
AU  - Jovanović, Maja
AU  - Bogdanović, Andrija
AU  - Trajković, Vladimir S.
AU  - Sabo, Tibor
AU  - Grgurić-Šipka, Sanja
AU  - Marković, Ivanka
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1215
AB  - Herein we describe the synthesis, characterization, and anticancer activity of novel p-cymeneruthenium(II) complexes containing methyl, ethyl, n-propyl, and n-butyl esters of (S, S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid. The results of IR, UV/Vis, ESIMS, (1)H, and (13)C NMR characterization reveal that ligand coordination occurs through nitrogen donor atoms of the ester ligands, with the organoruthenium moiety being kept in complex. These ruthenium(II) complexes are cytotoxic toward various cancer cell lines including leukemic HL-60, K562, and REH cells (IC(50) : 1.0-20.2 mu m), with the n-butyl ester complex being the most effective. It causes apoptotic cell death associated with mitochondrial depolarization, caspase activation, phosphatidylserine exposure, and DNA fragmentation. Importantly, the n-butyl ester complex is more effective against leukemic patients' blood mononuclear cells relative to those from healthy control subjects, thus indicating a fairly selective antileukemic action of Ru(II)-based compounds.
PB  - Wiley-Blackwell, Malden
T2  - ChemMedChem
T1  - Synthesis and in vitro Anticancer Activity of Ruthenium-Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-diacetate-Type Ligands
VL  - 6
IS  - 10
SP  - 1884
EP  - 1891
DO  - 10.1002/cmdc.201100232
ER  - 

@article{
author = "Savić, Aleksandar and Dulović, Marija and Poljarević, Jelena and Misirlić-Denčić, Sonja and Jovanović, Maja and Bogdanović, Andrija and Trajković, Vladimir S. and Sabo, Tibor and Grgurić-Šipka, Sanja and Marković, Ivanka",
year = "2011",
abstract = "Herein we describe the synthesis, characterization, and anticancer activity of novel p-cymeneruthenium(II) complexes containing methyl, ethyl, n-propyl, and n-butyl esters of (S, S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid. The results of IR, UV/Vis, ESIMS, (1)H, and (13)C NMR characterization reveal that ligand coordination occurs through nitrogen donor atoms of the ester ligands, with the organoruthenium moiety being kept in complex. These ruthenium(II) complexes are cytotoxic toward various cancer cell lines including leukemic HL-60, K562, and REH cells (IC(50) : 1.0-20.2 mu m), with the n-butyl ester complex being the most effective. It causes apoptotic cell death associated with mitochondrial depolarization, caspase activation, phosphatidylserine exposure, and DNA fragmentation. Importantly, the n-butyl ester complex is more effective against leukemic patients' blood mononuclear cells relative to those from healthy control subjects, thus indicating a fairly selective antileukemic action of Ru(II)-based compounds.",
publisher = "Wiley-Blackwell, Malden",
journal = "ChemMedChem",
title = "Synthesis and in vitro Anticancer Activity of Ruthenium-Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-diacetate-Type Ligands",
volume = "6",
number = "10",
pages = "1884-1891",
doi = "10.1002/cmdc.201100232"
}

Savić, A., Dulović, M., Poljarević, J., Misirlić-Denčić, S., Jovanović, M., Bogdanović, A., Trajković, V. S., Sabo, T., Grgurić-Šipka, S.,& Marković, I.. (2011). Synthesis and in vitro Anticancer Activity of Ruthenium-Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-diacetate-Type Ligands. in ChemMedChem
Wiley-Blackwell, Malden., 6(10), 1884-1891.
https://doi.org/10.1002/cmdc.201100232

Savić A, Dulović M, Poljarević J, Misirlić-Denčić S, Jovanović M, Bogdanović A, Trajković VS, Sabo T, Grgurić-Šipka S, Marković I. Synthesis and in vitro Anticancer Activity of Ruthenium-Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-diacetate-Type Ligands. in ChemMedChem. 2011;6(10):1884-1891.
doi:10.1002/cmdc.201100232 .

Savić, Aleksandar, Dulović, Marija, Poljarević, Jelena, Misirlić-Denčić, Sonja, Jovanović, Maja, Bogdanović, Andrija, Trajković, Vladimir S., Sabo, Tibor, Grgurić-Šipka, Sanja, Marković, Ivanka, "Synthesis and in vitro Anticancer Activity of Ruthenium-Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-diacetate-Type Ligands" in ChemMedChem, 6, no. 10 (2011):1884-1891,
https://doi.org/10.1002/cmdc.201100232 . .

TY  - JOUR
AU  - Lazić, Jelena
AU  - Vucicevic, Ljubica
AU  - Grgurić-Šipka, Sanja
AU  - Janjetovic, Kristina
AU  - Kaluđerović, Goran N.
AU  - Misirkic, Maja
AU  - Gruden-Pavlović, Maja
AU  - Popadić, Dušan
AU  - Paschke, Reinhard
AU  - Trajković, Vladimir S.
AU  - Sabo, Tibor
PY  - 2010
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1088
AB  - The present study describes the synthesis and anticancer activity of novel octahedral Pt-IV complexes with cyclohexyl functionalized ethylenediamine-N,N'-diacetate-type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s-cis is the preferred geometry of these Pt-IV complexes with tetradentate-coordinated (S,S)-ethylenediamineN,N'-di-2-(3-cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell-cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt-IV complexes against various cancer cell lines (IC50 range: 1.9-8.7 mu m) was higher than that of cisplatin (IC50 range: 10.9-67.0 mu m) and proceeded through completely different mechanisms. Cisplatin induced caspase-dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt-IV complexes caused rapid, caspase-independent, oxidative stress-mediated non-apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - ChemMedChem
T1  - Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands
VL  - 5
IS  - 6
SP  - 881
EP  - 889
DO  - 10.1002/cmdc.201000058
ER  - 

@article{
author = "Lazić, Jelena and Vucicevic, Ljubica and Grgurić-Šipka, Sanja and Janjetovic, Kristina and Kaluđerović, Goran N. and Misirkic, Maja and Gruden-Pavlović, Maja and Popadić, Dušan and Paschke, Reinhard and Trajković, Vladimir S. and Sabo, Tibor",
year = "2010",
abstract = "The present study describes the synthesis and anticancer activity of novel octahedral Pt-IV complexes with cyclohexyl functionalized ethylenediamine-N,N'-diacetate-type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s-cis is the preferred geometry of these Pt-IV complexes with tetradentate-coordinated (S,S)-ethylenediamineN,N'-di-2-(3-cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell-cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt-IV complexes against various cancer cell lines (IC50 range: 1.9-8.7 mu m) was higher than that of cisplatin (IC50 range: 10.9-67.0 mu m) and proceeded through completely different mechanisms. Cisplatin induced caspase-dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt-IV complexes caused rapid, caspase-independent, oxidative stress-mediated non-apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "ChemMedChem",
title = "Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands",
volume = "5",
number = "6",
pages = "881-889",
doi = "10.1002/cmdc.201000058"
}

Lazić, J., Vucicevic, L., Grgurić-Šipka, S., Janjetovic, K., Kaluđerović, G. N., Misirkic, M., Gruden-Pavlović, M., Popadić, D., Paschke, R., Trajković, V. S.,& Sabo, T.. (2010). Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands. in ChemMedChem
Wiley-V C H Verlag Gmbh, Weinheim., 5(6), 881-889.
https://doi.org/10.1002/cmdc.201000058

Lazić J, Vucicevic L, Grgurić-Šipka S, Janjetovic K, Kaluđerović GN, Misirkic M, Gruden-Pavlović M, Popadić D, Paschke R, Trajković VS, Sabo T. Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands. in ChemMedChem. 2010;5(6):881-889.
doi:10.1002/cmdc.201000058 .

Lazić, Jelena, Vucicevic, Ljubica, Grgurić-Šipka, Sanja, Janjetovic, Kristina, Kaluđerović, Goran N., Misirkic, Maja, Gruden-Pavlović, Maja, Popadić, Dušan, Paschke, Reinhard, Trajković, Vladimir S., Sabo, Tibor, "Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands" in ChemMedChem, 5, no. 6 (2010):881-889,
https://doi.org/10.1002/cmdc.201000058 . .

TY  - JOUR
AU  - Djinovic, Vesna M.
AU  - Glodjovic, Verica V.
AU  - Vasic, Gordana P.
AU  - Trajković, Vladimir S.
AU  - Klisurić, Olivera
AU  - Stanković, Slobodanka
AU  - Sabo, Tibor
AU  - Trifunović, Srećko R.
PY  - 2010
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1084
AB  - The syntheses of two novel platinum(IV) complexes of formula [PtX2(S,S-eddp)center dot nH(2)O (S,S-eddp = ethylenediamine-N,N'-di-S,S-2-propanoate ion, X = chlorido (1) or bromido (2), n = 4, 0) are reported. The complexes have been obtained by direct reaction of corresponding potassium hexahalogenidoplatinate(IV) with neutralized ethylenediamine-N,N'-di-S,S-2-propanoic acid (H-2-S,S-eddp). The complexes were characterized by elemental analysis, infrared, H-1 and C-13 NMR spectroscopy. The spectroscopically predicted geometrical configurations of the obtained complexes were confirmed by X-ray analyses of the crystal structures of the s-cis-[Pt(S,S-eddp)Cl-2]center dot 4H(2)O and uns-cis-[Pt(S,S-eddp)Br-2]. These complexes displayed significantly lower in vitro cytotoxicity in comparison to cisplatin. (c) 2010 Elsevier Ltd. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Polyhedron
T1  - Stereospecific ligands and their complexes. IV: Synthesis, characterization and cytotoxicity of novel platinum(IV) complexes with ethylenediamine-N,N '-di-S,S-2-propanoate and halogenido ligands: Crystal structure of s-cis-[Pt(S,S-eddp)Cl-2]center dot 4H(
VL  - 29
IS  - 8
SP  - 1933
EP  - 1938
DO  - 10.1016/j.poly.2010.03.004
ER  - 

@article{
author = "Djinovic, Vesna M. and Glodjovic, Verica V. and Vasic, Gordana P. and Trajković, Vladimir S. and Klisurić, Olivera and Stanković, Slobodanka and Sabo, Tibor and Trifunović, Srećko R.",
year = "2010",
abstract = "The syntheses of two novel platinum(IV) complexes of formula [PtX2(S,S-eddp)center dot nH(2)O (S,S-eddp = ethylenediamine-N,N'-di-S,S-2-propanoate ion, X = chlorido (1) or bromido (2), n = 4, 0) are reported. The complexes have been obtained by direct reaction of corresponding potassium hexahalogenidoplatinate(IV) with neutralized ethylenediamine-N,N'-di-S,S-2-propanoic acid (H-2-S,S-eddp). The complexes were characterized by elemental analysis, infrared, H-1 and C-13 NMR spectroscopy. The spectroscopically predicted geometrical configurations of the obtained complexes were confirmed by X-ray analyses of the crystal structures of the s-cis-[Pt(S,S-eddp)Cl-2]center dot 4H(2)O and uns-cis-[Pt(S,S-eddp)Br-2]. These complexes displayed significantly lower in vitro cytotoxicity in comparison to cisplatin. (c) 2010 Elsevier Ltd. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Polyhedron",
title = "Stereospecific ligands and their complexes. IV: Synthesis, characterization and cytotoxicity of novel platinum(IV) complexes with ethylenediamine-N,N '-di-S,S-2-propanoate and halogenido ligands: Crystal structure of s-cis-[Pt(S,S-eddp)Cl-2]center dot 4H(",
volume = "29",
number = "8",
pages = "1933-1938",
doi = "10.1016/j.poly.2010.03.004"
}

Djinovic, V. M., Glodjovic, V. V., Vasic, G. P., Trajković, V. S., Klisurić, O., Stanković, S., Sabo, T.,& Trifunović, S. R.. (2010). Stereospecific ligands and their complexes. IV: Synthesis, characterization and cytotoxicity of novel platinum(IV) complexes with ethylenediamine-N,N '-di-S,S-2-propanoate and halogenido ligands: Crystal structure of s-cis-[Pt(S,S-eddp)Cl-2]center dot 4H(. in Polyhedron
Pergamon-Elsevier Science Ltd, Oxford., 29(8), 1933-1938.
https://doi.org/10.1016/j.poly.2010.03.004

Djinovic VM, Glodjovic VV, Vasic GP, Trajković VS, Klisurić O, Stanković S, Sabo T, Trifunović SR. Stereospecific ligands and their complexes. IV: Synthesis, characterization and cytotoxicity of novel platinum(IV) complexes with ethylenediamine-N,N '-di-S,S-2-propanoate and halogenido ligands: Crystal structure of s-cis-[Pt(S,S-eddp)Cl-2]center dot 4H(. in Polyhedron. 2010;29(8):1933-1938.
doi:10.1016/j.poly.2010.03.004 .

Djinovic, Vesna M., Glodjovic, Verica V., Vasic, Gordana P., Trajković, Vladimir S., Klisurić, Olivera, Stanković, Slobodanka, Sabo, Tibor, Trifunović, Srećko R., "Stereospecific ligands and their complexes. IV: Synthesis, characterization and cytotoxicity of novel platinum(IV) complexes with ethylenediamine-N,N '-di-S,S-2-propanoate and halogenido ligands: Crystal structure of s-cis-[Pt(S,S-eddp)Cl-2]center dot 4H(" in Polyhedron, 29, no. 8 (2010):1933-1938,
https://doi.org/10.1016/j.poly.2010.03.004 . .

TY  - JOUR
AU  - Vučković, Ivan M.
AU  - Trajković, Vladimir S.
AU  - Macura, Slobodan
AU  - Tešević, Vele
AU  - Janaćković, Peđa T.
AU  - Milosavljević, Slobodan M.
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/854
AB  - A new tetrahydrofuranoid lignan named seselinone was isolated from the aerial parts of Seseli annuum, together with three known lignans (eudesmin, magnone A and hernone) and prenylated coumarin umbeffiprenin. Seselinone and eudesmin showed cytotoxic activity against C6 rat glioma cell cultures. Copyright (c) 2007 John Wiley & Sons, Ltd.
PB  - John Wiley & Sons Ltd, Chichester
T2  - Phytotherapy Research
T1  - A novel cytotoxic lignan from Seseli annuum L.
VL  - 21
IS  - 8
SP  - 790
EP  - 792
DO  - 10.1002/ptr.2152
ER  - 

@article{
author = "Vučković, Ivan M. and Trajković, Vladimir S. and Macura, Slobodan and Tešević, Vele and Janaćković, Peđa T. and Milosavljević, Slobodan M.",
year = "2007",
abstract = "A new tetrahydrofuranoid lignan named seselinone was isolated from the aerial parts of Seseli annuum, together with three known lignans (eudesmin, magnone A and hernone) and prenylated coumarin umbeffiprenin. Seselinone and eudesmin showed cytotoxic activity against C6 rat glioma cell cultures. Copyright (c) 2007 John Wiley & Sons, Ltd.",
publisher = "John Wiley & Sons Ltd, Chichester",
journal = "Phytotherapy Research",
title = "A novel cytotoxic lignan from Seseli annuum L.",
volume = "21",
number = "8",
pages = "790-792",
doi = "10.1002/ptr.2152"
}

Vučković, I. M., Trajković, V. S., Macura, S., Tešević, V., Janaćković, P. T.,& Milosavljević, S. M.. (2007). A novel cytotoxic lignan from Seseli annuum L.. in Phytotherapy Research
John Wiley & Sons Ltd, Chichester., 21(8), 790-792.
https://doi.org/10.1002/ptr.2152

Vučković IM, Trajković VS, Macura S, Tešević V, Janaćković PT, Milosavljević SM. A novel cytotoxic lignan from Seseli annuum L.. in Phytotherapy Research. 2007;21(8):790-792.
doi:10.1002/ptr.2152 .

Vučković, Ivan M., Trajković, Vladimir S., Macura, Slobodan, Tešević, Vele, Janaćković, Peđa T., Milosavljević, Slobodan M., "A novel cytotoxic lignan from Seseli annuum L." in Phytotherapy Research, 21, no. 8 (2007):790-792,
https://doi.org/10.1002/ptr.2152 . .

TY  - JOUR
AU  - Ferjančić, Zorana
AU  - Matović, Radomir
AU  - Čeković, Živorad
AU  - Jiang, Yi
AU  - Snyder, James P.
AU  - Trajković, Vladimir S.
AU  - Saičić, Radomir
PY  - 2006
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/798
AB  - A C,D-seco-paclitaxel derivative 26 was prepared from taxine and tested for biological activity. Chemical reactivity of the seco-compounds proved to be substantially modified, with respects to taxoids. The corresponding C,D-seco-taxoid does not show tubulin stabilizing activity or cytotoxicity. Explanation of these observations based on molecular modeling is provided. (c) 2006 Elsevier Ltd. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Tetrahedron
T1  - Synthesis, biology, and modeling of a C-4 carbonyl C,D-seco-taxoid
VL  - 62
IS  - 36
SP  - 8503
EP  - 8514
DO  - 10.1016/j.tet.2006.06.080
ER  - 

@article{
author = "Ferjančić, Zorana and Matović, Radomir and Čeković, Živorad and Jiang, Yi and Snyder, James P. and Trajković, Vladimir S. and Saičić, Radomir",
year = "2006",
abstract = "A C,D-seco-paclitaxel derivative 26 was prepared from taxine and tested for biological activity. Chemical reactivity of the seco-compounds proved to be substantially modified, with respects to taxoids. The corresponding C,D-seco-taxoid does not show tubulin stabilizing activity or cytotoxicity. Explanation of these observations based on molecular modeling is provided. (c) 2006 Elsevier Ltd. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Tetrahedron",
title = "Synthesis, biology, and modeling of a C-4 carbonyl C,D-seco-taxoid",
volume = "62",
number = "36",
pages = "8503-8514",
doi = "10.1016/j.tet.2006.06.080"
}

Ferjančić, Z., Matović, R., Čeković, Ž., Jiang, Y., Snyder, J. P., Trajković, V. S.,& Saičić, R.. (2006). Synthesis, biology, and modeling of a C-4 carbonyl C,D-seco-taxoid. in Tetrahedron
Pergamon-Elsevier Science Ltd, Oxford., 62(36), 8503-8514.
https://doi.org/10.1016/j.tet.2006.06.080

Ferjančić Z, Matović R, Čeković Ž, Jiang Y, Snyder JP, Trajković VS, Saičić R. Synthesis, biology, and modeling of a C-4 carbonyl C,D-seco-taxoid. in Tetrahedron. 2006;62(36):8503-8514.
doi:10.1016/j.tet.2006.06.080 .

Ferjančić, Zorana, Matović, Radomir, Čeković, Živorad, Jiang, Yi, Snyder, James P., Trajković, Vladimir S., Saičić, Radomir, "Synthesis, biology, and modeling of a C-4 carbonyl C,D-seco-taxoid" in Tetrahedron, 62, no. 36 (2006):8503-8514,
https://doi.org/10.1016/j.tet.2006.06.080 . .

TY  - JOUR
AU  - Markovic, M
AU  - Knezevic, N
AU  - Momčilović, Miljana
AU  - Grgurić-Šipka, Sanja
AU  - Harhaji-Trajkovic, Ljubica
AU  - Trajković, Vladimir S.
AU  - Stojkovic, MM
AU  - Sabo, Tibor
AU  - Miljković, Đorđe
PY  - 2005
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/718
AB  - There has been a continuing effort for the discovery of novel platinum(IV)-based antitumor compounds with better therapeutic performances than cisplatin. In the present work, the anticancer action of recently synthesized Pt(IV)-based complex [Pt(HPxSC)Cl-3] was investigated using rat and human astrocytoma cell lines C6 and U251. [Pt(HPxSC)Cl-3] markedly reduced the number of cultured astrocytoma Cells (IC50, 80 mu M), as determined by crystal violet assay. The Pt(IV) complex induced apoptotic death of tumor cells, as flow cytometry analysis of the propidium iodide-stained cellular DNA revealed approx. 30% of hypodiploid cells in [Pt(HPxSC)Cl-3]-treated astrocytoma cell cultures. On the other hand, [Pt(HPxSC)Cl-3] at 200 mu M did not affect the viability of rat primary astrocytes, unlike the established anticancer drug cisplatin, which displayed high toxicity toward both astrocytoma cells (IC50, 15 mu M) and primary astrocytes (IC50, 20 mu M). Moreover, [Pt(HPxSC)Cl-3] at 100 mu M did not interfere with the ability of rat peritoneal macrophages to produce important antitumor molecules nitric oxide and tumor necrosis factor-a. Finally, we assessed the ability of [Pt(HPxSC)Cl-3] to restrain growth of some bacterial and yeast strains, but it showed rather limited antimicrobial activity. (c) 2005 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - European Journal of Pharmacology
T1  - [Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties
VL  - 517
IS  - 1-2
SP  - 28
EP  - 34
DO  - 10.1016/j.ejphar.2005.05.038
ER  - 

@article{
author = "Markovic, M and Knezevic, N and Momčilović, Miljana and Grgurić-Šipka, Sanja and Harhaji-Trajkovic, Ljubica and Trajković, Vladimir S. and Stojkovic, MM and Sabo, Tibor and Miljković, Đorđe",
year = "2005",
abstract = "There has been a continuing effort for the discovery of novel platinum(IV)-based antitumor compounds with better therapeutic performances than cisplatin. In the present work, the anticancer action of recently synthesized Pt(IV)-based complex [Pt(HPxSC)Cl-3] was investigated using rat and human astrocytoma cell lines C6 and U251. [Pt(HPxSC)Cl-3] markedly reduced the number of cultured astrocytoma Cells (IC50, 80 mu M), as determined by crystal violet assay. The Pt(IV) complex induced apoptotic death of tumor cells, as flow cytometry analysis of the propidium iodide-stained cellular DNA revealed approx. 30% of hypodiploid cells in [Pt(HPxSC)Cl-3]-treated astrocytoma cell cultures. On the other hand, [Pt(HPxSC)Cl-3] at 200 mu M did not affect the viability of rat primary astrocytes, unlike the established anticancer drug cisplatin, which displayed high toxicity toward both astrocytoma cells (IC50, 15 mu M) and primary astrocytes (IC50, 20 mu M). Moreover, [Pt(HPxSC)Cl-3] at 100 mu M did not interfere with the ability of rat peritoneal macrophages to produce important antitumor molecules nitric oxide and tumor necrosis factor-a. Finally, we assessed the ability of [Pt(HPxSC)Cl-3] to restrain growth of some bacterial and yeast strains, but it showed rather limited antimicrobial activity. (c) 2005 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "European Journal of Pharmacology",
title = "[Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties",
volume = "517",
number = "1-2",
pages = "28-34",
doi = "10.1016/j.ejphar.2005.05.038"
}

Markovic, M., Knezevic, N., Momčilović, M., Grgurić-Šipka, S., Harhaji-Trajkovic, L., Trajković, V. S., Stojkovic, M., Sabo, T.,& Miljković, Đ.. (2005). [Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties. in European Journal of Pharmacology
Elsevier Science Bv, Amsterdam., 517(1-2), 28-34.
https://doi.org/10.1016/j.ejphar.2005.05.038

Markovic M, Knezevic N, Momčilović M, Grgurić-Šipka S, Harhaji-Trajkovic L, Trajković VS, Stojkovic M, Sabo T, Miljković Đ. [Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties. in European Journal of Pharmacology. 2005;517(1-2):28-34.
doi:10.1016/j.ejphar.2005.05.038 .

Markovic, M, Knezevic, N, Momčilović, Miljana, Grgurić-Šipka, Sanja, Harhaji-Trajkovic, Ljubica, Trajković, Vladimir S., Stojkovic, MM, Sabo, Tibor, Miljković, Đorđe, "[Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties" in European Journal of Pharmacology, 517, no. 1-2 (2005):28-34,
https://doi.org/10.1016/j.ejphar.2005.05.038 . .

TY  - JOUR
AU  - Kaludjerovic, GN
AU  - Miljković, Đorđe
AU  - Momčilović, Miljana
AU  - Djinovic, VM
AU  - Stojkovic, MM
AU  - Sabo, Tibor
AU  - Trajković, Vladimir S.
PY  - 2005
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/719
AB  - The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)-based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum-based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)-based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine-N,N'-di-3-propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress-independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical-mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy. (C) 2005 Wiley-Liss, Inc.
PB  - Wiley, Hoboken
T2  - International Journal of Cancer
T1  - Novel platinum(IV) complexes induce rapid tumor cell death in vitro
VL  - 116
IS  - 3
SP  - 479
EP  - 486
DO  - 10.1002/ijc.21080
ER  - 

@article{
author = "Kaludjerovic, GN and Miljković, Đorđe and Momčilović, Miljana and Djinovic, VM and Stojkovic, MM and Sabo, Tibor and Trajković, Vladimir S.",
year = "2005",
abstract = "The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)-based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum-based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)-based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine-N,N'-di-3-propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress-independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical-mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy. (C) 2005 Wiley-Liss, Inc.",
publisher = "Wiley, Hoboken",
journal = "International Journal of Cancer",
title = "Novel platinum(IV) complexes induce rapid tumor cell death in vitro",
volume = "116",
number = "3",
pages = "479-486",
doi = "10.1002/ijc.21080"
}

Kaludjerovic, G., Miljković, Đ., Momčilović, M., Djinovic, V., Stojkovic, M., Sabo, T.,& Trajković, V. S.. (2005). Novel platinum(IV) complexes induce rapid tumor cell death in vitro. in International Journal of Cancer
Wiley, Hoboken., 116(3), 479-486.
https://doi.org/10.1002/ijc.21080

Kaludjerovic G, Miljković Đ, Momčilović M, Djinovic V, Stojkovic M, Sabo T, Trajković VS. Novel platinum(IV) complexes induce rapid tumor cell death in vitro. in International Journal of Cancer. 2005;116(3):479-486.
doi:10.1002/ijc.21080 .

Kaludjerovic, GN, Miljković, Đorđe, Momčilović, Miljana, Djinovic, VM, Stojkovic, MM, Sabo, Tibor, Trajković, Vladimir S., "Novel platinum(IV) complexes induce rapid tumor cell death in vitro" in International Journal of Cancer, 116, no. 3 (2005):479-486,
https://doi.org/10.1002/ijc.21080 . .

TY  - JOUR
AU  - Mijatovic, S
AU  - Maksimovic-Ivanic, D
AU  - Radovic, J
AU  - Miljković, Đorđe
AU  - Kaludjerovic, GN
AU  - Sabo, Tibor
AU  - Trajković, Vladimir S.
PY  - 2005
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/733
AB  - The present study describes the ability of an anthraquinone derivative aloe emodin (AE) to reduce the cytotoxic activity of the platinum(II)-based anticancer agent cisplatin toward murine L929 fibrosarcoma and C6 glioma cell lines. The protective effect of AE was demonstrated by MTT and crystal violet assays for cell viability, and involved supression of cisplatin-induced apoptosis and necrosis, as assessed by lactate dehydrogenase release and flow cytometric analysis of DNA fragmentation or phosphatidylserine exposure. Cell-based ELISA and Western blot analysis revealed that AE abolished cisplatin-triggered activation of extracellular signal-regulated kinase (ERK) in tumor cells, while activation of c-Jun N-terminal kinase was not significantly altered. A selective blockade of ERK activation with PD98059 mimicked the protective effect of AE treatment in both tumor cell lines. Moreover, AE failed to protect tumor cells against the ERK-independent toxicity of the Pt(IV)-based complex tetrachloro(O,O-dibutyl-ethylenediamine-N,N'-di-3-propanoate)platinum(IV). Taken together, these data indicate that herbal anthraquinone AE can downregulate the anticancer activity of cisplatin by blocking the activation of ERK in tumor cells.
PB  - Birkhauser Verlag Ag, Basel
T2  - Cellular and Molecular Life Sciences / CMLS
T1  - Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin
VL  - 62
IS  - 11
SP  - 1275
EP  - 1282
DO  - 10.1007/s00018-005-5041-3
ER  - 

@article{
author = "Mijatovic, S and Maksimovic-Ivanic, D and Radovic, J and Miljković, Đorđe and Kaludjerovic, GN and Sabo, Tibor and Trajković, Vladimir S.",
year = "2005",
abstract = "The present study describes the ability of an anthraquinone derivative aloe emodin (AE) to reduce the cytotoxic activity of the platinum(II)-based anticancer agent cisplatin toward murine L929 fibrosarcoma and C6 glioma cell lines. The protective effect of AE was demonstrated by MTT and crystal violet assays for cell viability, and involved supression of cisplatin-induced apoptosis and necrosis, as assessed by lactate dehydrogenase release and flow cytometric analysis of DNA fragmentation or phosphatidylserine exposure. Cell-based ELISA and Western blot analysis revealed that AE abolished cisplatin-triggered activation of extracellular signal-regulated kinase (ERK) in tumor cells, while activation of c-Jun N-terminal kinase was not significantly altered. A selective blockade of ERK activation with PD98059 mimicked the protective effect of AE treatment in both tumor cell lines. Moreover, AE failed to protect tumor cells against the ERK-independent toxicity of the Pt(IV)-based complex tetrachloro(O,O-dibutyl-ethylenediamine-N,N'-di-3-propanoate)platinum(IV). Taken together, these data indicate that herbal anthraquinone AE can downregulate the anticancer activity of cisplatin by blocking the activation of ERK in tumor cells.",
publisher = "Birkhauser Verlag Ag, Basel",
journal = "Cellular and Molecular Life Sciences / CMLS",
title = "Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin",
volume = "62",
number = "11",
pages = "1275-1282",
doi = "10.1007/s00018-005-5041-3"
}

Mijatovic, S., Maksimovic-Ivanic, D., Radovic, J., Miljković, Đ., Kaludjerovic, G., Sabo, T.,& Trajković, V. S.. (2005). Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin. in Cellular and Molecular Life Sciences / CMLS
Birkhauser Verlag Ag, Basel., 62(11), 1275-1282.
https://doi.org/10.1007/s00018-005-5041-3

Mijatovic S, Maksimovic-Ivanic D, Radovic J, Miljković Đ, Kaludjerovic G, Sabo T, Trajković VS. Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin. in Cellular and Molecular Life Sciences / CMLS. 2005;62(11):1275-1282.
doi:10.1007/s00018-005-5041-3 .

Mijatovic, S, Maksimovic-Ivanic, D, Radovic, J, Miljković, Đorđe, Kaludjerovic, GN, Sabo, Tibor, Trajković, Vladimir S., "Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin" in Cellular and Molecular Life Sciences / CMLS, 62, no. 11 (2005):1275-1282,
https://doi.org/10.1007/s00018-005-5041-3 . .

TY  - JOUR
AU  - Djinovic, V
AU  - Momčilović, Miljana
AU  - Grgurić-Šipka, Sanja
AU  - Trajković, Vladimir S.
AU  - Stojkovic, MM
AU  - Miljković, Đorđe
AU  - Sabo, Tibor
PY  - 2004
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/672
AB  - A novel class of ruthenium (111) complexes of formulas K[Ru(sar)(2)Cl-2] - 1/2HO and K-2[Ru(dmgly)Cl-4] . 1/2H(2)O, containing biden2 tate chelates N-methylglycine (sarcosine, sar) or N,N-dimethylglycine (dnigly) and additional chloro ligands were synthesized. The complexes have been obtained by direct reaction of ruthenium(III) chloride with corresponding bidentate ligand followed by addition of base (KOH). These new complexes were characterized by elemental analysis, IR and electronic absorption spectroscopy. As astrocytomas, the most common of all brain tumors, are still very difficult to treat, we examined the influence of newly synthesized ruthenium-based complexes, as well as the earlier synthesized analogue platinum(IV) complexes [Pt(dmglY)(2)Cl-2], [Pt(sar)(2)Br-2] and [Pt(dmgly)(2)Br-2] on rat astrocytoma C6 cells in vitro. Among these complexes only K-2[Ru(dmglY)Cl-4].2H(2)O and [Pt(dMgIY)(2)Br-2] markedly inhibited the viability of non-confluent C6 cells. Furthermore, only complex K-2[Ru(dmgly)Cl4] .2H20 was able to reduce viability in confluent C6 cultures. Importantly, this complex was not toxic to primary rat astrocytes or macrophages. Having in mind that appropriate chemotherapy should be effective against tumor cells without harming normal tissues, complex K,[Ru(dmglY)Cl-4] - 2H(2)O could be a promising agent for developing therapeutics against astrocytomas. (C) 2004 Elsevier Inc. All rights reserved.
PB  - Elsevier Science Inc, New York
T2  - Journal of Inorganic Biochemistry
T1  - Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes
VL  - 98
IS  - 12
SP  - 2168
EP  - 2173
DO  - 10.1016/j.jinorgbio.2004.10.007
ER  - 

@article{
author = "Djinovic, V and Momčilović, Miljana and Grgurić-Šipka, Sanja and Trajković, Vladimir S. and Stojkovic, MM and Miljković, Đorđe and Sabo, Tibor",
year = "2004",
abstract = "A novel class of ruthenium (111) complexes of formulas K[Ru(sar)(2)Cl-2] - 1/2HO and K-2[Ru(dmgly)Cl-4] . 1/2H(2)O, containing biden2 tate chelates N-methylglycine (sarcosine, sar) or N,N-dimethylglycine (dnigly) and additional chloro ligands were synthesized. The complexes have been obtained by direct reaction of ruthenium(III) chloride with corresponding bidentate ligand followed by addition of base (KOH). These new complexes were characterized by elemental analysis, IR and electronic absorption spectroscopy. As astrocytomas, the most common of all brain tumors, are still very difficult to treat, we examined the influence of newly synthesized ruthenium-based complexes, as well as the earlier synthesized analogue platinum(IV) complexes [Pt(dmglY)(2)Cl-2], [Pt(sar)(2)Br-2] and [Pt(dmgly)(2)Br-2] on rat astrocytoma C6 cells in vitro. Among these complexes only K-2[Ru(dmglY)Cl-4].2H(2)O and [Pt(dMgIY)(2)Br-2] markedly inhibited the viability of non-confluent C6 cells. Furthermore, only complex K-2[Ru(dmgly)Cl4] .2H20 was able to reduce viability in confluent C6 cultures. Importantly, this complex was not toxic to primary rat astrocytes or macrophages. Having in mind that appropriate chemotherapy should be effective against tumor cells without harming normal tissues, complex K,[Ru(dmglY)Cl-4] - 2H(2)O could be a promising agent for developing therapeutics against astrocytomas. (C) 2004 Elsevier Inc. All rights reserved.",
publisher = "Elsevier Science Inc, New York",
journal = "Journal of Inorganic Biochemistry",
title = "Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes",
volume = "98",
number = "12",
pages = "2168-2173",
doi = "10.1016/j.jinorgbio.2004.10.007"
}

Djinovic, V., Momčilović, M., Grgurić-Šipka, S., Trajković, V. S., Stojkovic, M., Miljković, Đ.,& Sabo, T.. (2004). Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes. in Journal of Inorganic Biochemistry
Elsevier Science Inc, New York., 98(12), 2168-2173.
https://doi.org/10.1016/j.jinorgbio.2004.10.007

Djinovic V, Momčilović M, Grgurić-Šipka S, Trajković VS, Stojkovic M, Miljković Đ, Sabo T. Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes. in Journal of Inorganic Biochemistry. 2004;98(12):2168-2173.
doi:10.1016/j.jinorgbio.2004.10.007 .

Djinovic, V, Momčilović, Miljana, Grgurić-Šipka, Sanja, Trajković, Vladimir S., Stojkovic, MM, Miljković, Đorđe, Sabo, Tibor, "Novel ruthenium complex K-2[Ru(dmgly)Cl-4] center dot 2H(2)O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes" in Journal of Inorganic Biochemistry, 98, no. 12 (2004):2168-2173,
https://doi.org/10.1016/j.jinorgbio.2004.10.007 . .