TY  - CONF
AU  - Krstić, Milena
AU  - Santibanez, Juan Francisco
AU  - Poljarević, Jelena
AU  - Grgurić-Šipka, Sanja
AU  - Borozan, Sunčica
PY  - 2023
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/3795
AB  - C-Jun N-terminalne kinaze (JNK) spadaju u mitogen-aktivirane protein kinaze (MAPK) i
imaju važnu ulogu u kontroli niza ćelijskih procesa uključujući proliferaciju,
kancerogenezu i apoptozu. Kompleksi rutenijuma pokazali su izuzetan potencijal kao
mogući citostatici. Upravo iz ovih razloga ispitivan je mehanizam delovanja kompleksa
Ru(II) sa N-alkilfenotiazinima (hlorpromazinom, trifluoperazinom i tioridazinom) na
signalne parametre (t-JNK, p-JNK i β-aktin) u THP-1 ćelijama humane leukemije. U
ćelijama tretiranim kompleksom sa fluoperazinom u koncentraciji od 10 μM (IC50 je 10,5
μM) ekspresija t-JNK povećana je za 47,45%, dok je ekspresija p-JNK dvostruko veća u
poređenju sa netretiranim ćelijama, što sugeriše da su t-JNK i p-JNK uključeni u apoptozu
ovih ćelija.
AB  - The c-Jun N-terminal kinase (JNK) belongs to the family of mitogen-activated protein
kinases (MAPKs) that play an important role in the control of a number of celular
processes, including proliferation, cancerogenesis and apoptosis. Ruthenium complexes
have shown remarkable potential as possible cytostatics. Precisely for these reasons, the
mechanism of action of Ru(II) complexes with N-alkylphenothiazines (chlorpromazine,
trifluoperazine, and thioridazine) on signalling parameters (t-JNK, p-JNK and β-actin) in
THP-1 human leucemic cells was investigated. In cells treated with fluoperazine complex
at a concentration of 10 μM (IC50 is 10.5 μM), an increased expression of t-JNK by 47.45%
was found while the expression of p-JNK was twice higher compared to untreated cells,
suggesting that t-JNK and p-JNK are involved in the apoptosis of these cells.
PB  - Beograd : Srpsko hemijsko društvo
C3  - 59. Savetovanje Srpskog hemijskog društva, Novi Sad, 1 - 2. jun 2023
T1  - Ekspresija JNK kinaza u THP-1 celijama tretiranim Ru(II) kompleksima
T1  - Expression of JNK kinases in THP-1 cells treated with Ru(II) complexes
SP  - 51
EP  - 51
UR  - https://hdl.handle.net/21.15107/rcub_veterinar_3795
ER  - 

@conference{
author = "Krstić, Milena and Santibanez, Juan Francisco and Poljarević, Jelena and Grgurić-Šipka, Sanja and Borozan, Sunčica",
year = "2023",
abstract = "C-Jun N-terminalne kinaze (JNK) spadaju u mitogen-aktivirane protein kinaze (MAPK) i
imaju važnu ulogu u kontroli niza ćelijskih procesa uključujući proliferaciju,
kancerogenezu i apoptozu. Kompleksi rutenijuma pokazali su izuzetan potencijal kao
mogući citostatici. Upravo iz ovih razloga ispitivan je mehanizam delovanja kompleksa
Ru(II) sa N-alkilfenotiazinima (hlorpromazinom, trifluoperazinom i tioridazinom) na
signalne parametre (t-JNK, p-JNK i β-aktin) u THP-1 ćelijama humane leukemije. U
ćelijama tretiranim kompleksom sa fluoperazinom u koncentraciji od 10 μM (IC50 je 10,5
μM) ekspresija t-JNK povećana je za 47,45%, dok je ekspresija p-JNK dvostruko veća u
poređenju sa netretiranim ćelijama, što sugeriše da su t-JNK i p-JNK uključeni u apoptozu
ovih ćelija., The c-Jun N-terminal kinase (JNK) belongs to the family of mitogen-activated protein
kinases (MAPKs) that play an important role in the control of a number of celular
processes, including proliferation, cancerogenesis and apoptosis. Ruthenium complexes
have shown remarkable potential as possible cytostatics. Precisely for these reasons, the
mechanism of action of Ru(II) complexes with N-alkylphenothiazines (chlorpromazine,
trifluoperazine, and thioridazine) on signalling parameters (t-JNK, p-JNK and β-actin) in
THP-1 human leucemic cells was investigated. In cells treated with fluoperazine complex
at a concentration of 10 μM (IC50 is 10.5 μM), an increased expression of t-JNK by 47.45%
was found while the expression of p-JNK was twice higher compared to untreated cells,
suggesting that t-JNK and p-JNK are involved in the apoptosis of these cells.",
publisher = "Beograd : Srpsko hemijsko društvo",
journal = "59. Savetovanje Srpskog hemijskog društva, Novi Sad, 1 - 2. jun 2023",
title = "Ekspresija JNK kinaza u THP-1 celijama tretiranim Ru(II) kompleksima, Expression of JNK kinases in THP-1 cells treated with Ru(II) complexes",
pages = "51-51",
url = "https://hdl.handle.net/21.15107/rcub_veterinar_3795"
}

Krstić, M., Santibanez, J. F., Poljarević, J., Grgurić-Šipka, S.,& Borozan, S.. (2023). Ekspresija JNK kinaza u THP-1 celijama tretiranim Ru(II) kompleksima. in 59. Savetovanje Srpskog hemijskog društva, Novi Sad, 1 - 2. jun 2023
Beograd : Srpsko hemijsko društvo., 51-51.
https://hdl.handle.net/21.15107/rcub_veterinar_3795

Krstić M, Santibanez JF, Poljarević J, Grgurić-Šipka S, Borozan S. Ekspresija JNK kinaza u THP-1 celijama tretiranim Ru(II) kompleksima. in 59. Savetovanje Srpskog hemijskog društva, Novi Sad, 1 - 2. jun 2023. 2023;:51-51.
https://hdl.handle.net/21.15107/rcub_veterinar_3795 .

Krstić, Milena, Santibanez, Juan Francisco, Poljarević, Jelena, Grgurić-Šipka, Sanja, Borozan, Sunčica, "Ekspresija JNK kinaza u THP-1 celijama tretiranim Ru(II) kompleksima" in 59. Savetovanje Srpskog hemijskog društva, Novi Sad, 1 - 2. jun 2023 (2023):51-51,
https://hdl.handle.net/21.15107/rcub_veterinar_3795 .

TY  - CONF
AU  - Petrović, Tamara
AU  - Gligorijević, Nevenka
AU  - Belaj, Ferdinand
AU  - Grgurić-Šipka, Sanja
AU  - Nikolić, Stefan
AU  - Krstić, Milena
AU  - Poljarević, Jelena
AU  - Mihajlović-Lalić, Ljiljana E.
PY  - 2022
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/2798
AB  - Rhenium complexes merit particular attention in the area of metallodrug design due to rhenium’s broad spectrum of oxidation states and consequently, the possibility to design compounds of a great structural diversity. Thus, the synthesis, chemical characterization and antitumor activity in vitro of the three Re(V) complexes is described. Novel compounds were obtained via reaction of [ReOCl3(PPh3)2] with corresponding ligands (pyridine-2-carboxylic acid, 3-methylpyridine-2-carboxylic acid and 6-methylpyridine- 2-carboxylic acid) in acetonitrile at 78 °C for 3h. The complexes were fully characterized using NMR, IR, MS and elemental analysis. Their octahedral geometry with bidentate N^O ligand was confirmed by X-ray diffraction analysis. Antiproliferative effect was determined by MTT assay and only the complex with pyridine-2-carboxylic acid (1) showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cells MDA-MB-231 with IC50 68.90 ±
1.73 μM and pancreatic adenocarcinoma cells PANC-1 with IC50 69.8 ± 2.3 μM. Drug combination studies in PANC-1 cells with 1 and Verapamil hydrochloride (VRP) showed slight arrest of cell cycle in the S phase and also it increase its antiproliferative potential to IC50 51.4 ± 2.8 μM. Part of the research included a depletion of the glutathione (GSH) level by L-buthionine-sulfoximine (L-BSO) at sub-toxic concentrations (100 μM) in PANC-1 cells which caused an increase of activity of 1 to the IC50 57.67 ± 6.51 μM.
C3  - Osterreichische Chemietage, Wienna, Austria, September 20-22, 2022
T1  - Oxorhenium(V) complexes in the drug combination study
SP  - 90
EP  - 90
UR  - https://hdl.handle.net/21.15107/rcub_veterinar_2798
ER  - 

@conference{
author = "Petrović, Tamara and Gligorijević, Nevenka and Belaj, Ferdinand and Grgurić-Šipka, Sanja and Nikolić, Stefan and Krstić, Milena and Poljarević, Jelena and Mihajlović-Lalić, Ljiljana E.",
year = "2022",
abstract = "Rhenium complexes merit particular attention in the area of metallodrug design due to rhenium’s broad spectrum of oxidation states and consequently, the possibility to design compounds of a great structural diversity. Thus, the synthesis, chemical characterization and antitumor activity in vitro of the three Re(V) complexes is described. Novel compounds were obtained via reaction of [ReOCl3(PPh3)2] with corresponding ligands (pyridine-2-carboxylic acid, 3-methylpyridine-2-carboxylic acid and 6-methylpyridine- 2-carboxylic acid) in acetonitrile at 78 °C for 3h. The complexes were fully characterized using NMR, IR, MS and elemental analysis. Their octahedral geometry with bidentate N^O ligand was confirmed by X-ray diffraction analysis. Antiproliferative effect was determined by MTT assay and only the complex with pyridine-2-carboxylic acid (1) showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cells MDA-MB-231 with IC50 68.90 ±
1.73 μM and pancreatic adenocarcinoma cells PANC-1 with IC50 69.8 ± 2.3 μM. Drug combination studies in PANC-1 cells with 1 and Verapamil hydrochloride (VRP) showed slight arrest of cell cycle in the S phase and also it increase its antiproliferative potential to IC50 51.4 ± 2.8 μM. Part of the research included a depletion of the glutathione (GSH) level by L-buthionine-sulfoximine (L-BSO) at sub-toxic concentrations (100 μM) in PANC-1 cells which caused an increase of activity of 1 to the IC50 57.67 ± 6.51 μM.",
journal = "Osterreichische Chemietage, Wienna, Austria, September 20-22, 2022",
title = "Oxorhenium(V) complexes in the drug combination study",
pages = "90-90",
url = "https://hdl.handle.net/21.15107/rcub_veterinar_2798"
}

Petrović, T., Gligorijević, N., Belaj, F., Grgurić-Šipka, S., Nikolić, S., Krstić, M., Poljarević, J.,& Mihajlović-Lalić, L. E.. (2022). Oxorhenium(V) complexes in the drug combination study. in Osterreichische Chemietage, Wienna, Austria, September 20-22, 2022, 90-90.
https://hdl.handle.net/21.15107/rcub_veterinar_2798

Petrović T, Gligorijević N, Belaj F, Grgurić-Šipka S, Nikolić S, Krstić M, Poljarević J, Mihajlović-Lalić LE. Oxorhenium(V) complexes in the drug combination study. in Osterreichische Chemietage, Wienna, Austria, September 20-22, 2022. 2022;:90-90.
https://hdl.handle.net/21.15107/rcub_veterinar_2798 .

Petrović, Tamara, Gligorijević, Nevenka, Belaj, Ferdinand, Grgurić-Šipka, Sanja, Nikolić, Stefan, Krstić, Milena, Poljarević, Jelena, Mihajlović-Lalić, Ljiljana E., "Oxorhenium(V) complexes in the drug combination study" in Osterreichische Chemietage, Wienna, Austria, September 20-22, 2022 (2022):90-90,
https://hdl.handle.net/21.15107/rcub_veterinar_2798 .

TY  - JOUR
AU  - Tadić, Ana
AU  - Poljarević, Jelena
AU  - Krstić, Milena
AU  - Kajzerberger, Marijana
AU  - Aranđelović, Sandra
AU  - Radulović, Siniša
AU  - Kakoulidou, Chrisoula
AU  - Papadopoulos, Athanasios N.
AU  - Psomas, George
AU  - Grgurić-Šipka, Sanja
PY  - 2018
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/1639
AB  - Two non-steroidal antiinflammatory drugs indomethacin and mefenamic acid were coordinated to Ru(II)-arenes to afford four new complexes. The cytotoxic activities of the ligands and ruthenium complexes were tested in three human cancer cell lines (K562, A549, MDA-MB-231) and non-tumour human fetal lung fibroblast cells (MRC-5) by MTT assay. Cytotoxicity studies revealed that indomethacin Ru(II)-arene complexes 1 and 3 displayed good cytotoxicity and apparent cytoselective profiles. The IC50 values obtained in leukemia K562 cells were comparable to those of cisplatin (10.3 mu M (CDDP), 11.9 mu M (1) and 13.2 mu M (3)). Flow cytometric analysis of 1 and 3 in triple-negative breast cancer MDA-MB-231 cells revealed an interesting mechanism of action. At IC50 concentrations, 1 and 3 arrested cell cycle progression in S phase and caused rapid accumulation of cells in sub-G1 phase (up to 48%), while Annexin V-FITC/PI staining showed simultaneous occurrence of apoptotic and necrotic cell populations at approximately similar levels of 20%. Measurement of reactive oxygen species (ROS) production by DCFH-DA staining confirmed the potential of 1 and 3 to increase ROS even more than cisplatin. The interaction of the complexes with serum albumins showed their potential ability to bind tightly and reversibly to albumins. The affinity of the complexes to calf-thymus DNA was investigated by UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for competitive studies of the complexes with ethidium bromide, revealing that their interaction probably occurs via intercalation. Taken together, the results strongly suggest the potential of complexes 1 and 3 to alter cell cycle progression and cause DNA-damage by means of direct DNA-binding or indirectly by ROS production.
PB  - Royal Soc Chemistry, Cambridge
T2  - New Journal of Chemistry
T1  - Ruthenium-arene complexes with NSAIDs: synthesis, characterization and bioactivity
VL  - 42
IS  - 4
SP  - 3001
EP  - 3019
DO  - 10.1039/c7nj04416j
ER  - 

@article{
author = "Tadić, Ana and Poljarević, Jelena and Krstić, Milena and Kajzerberger, Marijana and Aranđelović, Sandra and Radulović, Siniša and Kakoulidou, Chrisoula and Papadopoulos, Athanasios N. and Psomas, George and Grgurić-Šipka, Sanja",
year = "2018",
abstract = "Two non-steroidal antiinflammatory drugs indomethacin and mefenamic acid were coordinated to Ru(II)-arenes to afford four new complexes. The cytotoxic activities of the ligands and ruthenium complexes were tested in three human cancer cell lines (K562, A549, MDA-MB-231) and non-tumour human fetal lung fibroblast cells (MRC-5) by MTT assay. Cytotoxicity studies revealed that indomethacin Ru(II)-arene complexes 1 and 3 displayed good cytotoxicity and apparent cytoselective profiles. The IC50 values obtained in leukemia K562 cells were comparable to those of cisplatin (10.3 mu M (CDDP), 11.9 mu M (1) and 13.2 mu M (3)). Flow cytometric analysis of 1 and 3 in triple-negative breast cancer MDA-MB-231 cells revealed an interesting mechanism of action. At IC50 concentrations, 1 and 3 arrested cell cycle progression in S phase and caused rapid accumulation of cells in sub-G1 phase (up to 48%), while Annexin V-FITC/PI staining showed simultaneous occurrence of apoptotic and necrotic cell populations at approximately similar levels of 20%. Measurement of reactive oxygen species (ROS) production by DCFH-DA staining confirmed the potential of 1 and 3 to increase ROS even more than cisplatin. The interaction of the complexes with serum albumins showed their potential ability to bind tightly and reversibly to albumins. The affinity of the complexes to calf-thymus DNA was investigated by UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for competitive studies of the complexes with ethidium bromide, revealing that their interaction probably occurs via intercalation. Taken together, the results strongly suggest the potential of complexes 1 and 3 to alter cell cycle progression and cause DNA-damage by means of direct DNA-binding or indirectly by ROS production.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "New Journal of Chemistry",
title = "Ruthenium-arene complexes with NSAIDs: synthesis, characterization and bioactivity",
volume = "42",
number = "4",
pages = "3001-3019",
doi = "10.1039/c7nj04416j"
}

Tadić, A., Poljarević, J., Krstić, M., Kajzerberger, M., Aranđelović, S., Radulović, S., Kakoulidou, C., Papadopoulos, A. N., Psomas, G.,& Grgurić-Šipka, S.. (2018). Ruthenium-arene complexes with NSAIDs: synthesis, characterization and bioactivity. in New Journal of Chemistry
Royal Soc Chemistry, Cambridge., 42(4), 3001-3019.
https://doi.org/10.1039/c7nj04416j

Tadić A, Poljarević J, Krstić M, Kajzerberger M, Aranđelović S, Radulović S, Kakoulidou C, Papadopoulos AN, Psomas G, Grgurić-Šipka S. Ruthenium-arene complexes with NSAIDs: synthesis, characterization and bioactivity. in New Journal of Chemistry. 2018;42(4):3001-3019.
doi:10.1039/c7nj04416j .

Tadić, Ana, Poljarević, Jelena, Krstić, Milena, Kajzerberger, Marijana, Aranđelović, Sandra, Radulović, Siniša, Kakoulidou, Chrisoula, Papadopoulos, Athanasios N., Psomas, George, Grgurić-Šipka, Sanja, "Ruthenium-arene complexes with NSAIDs: synthesis, characterization and bioactivity" in New Journal of Chemistry, 42, no. 4 (2018):3001-3019,
https://doi.org/10.1039/c7nj04416j . .

TY  - JOUR
AU  - Krstić, Milena
AU  - Borozan, Sunčica
AU  - Sovilj, Sofija P.
AU  - Grgurić-Šipka, Sanja
AU  - Poljarević, Jelena
PY  - 2016
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/1353
AB  - The purpose of the present study was to investigate and compare the effects of two ruthenium complexes with trifluoperazine on acethylcholinesterase enzyme activity and lactate dehydrogenase levels in vivo under physiological conditions in rats blood. Complexes 1 and 2 showed positive effects on acethylcholinesterase at all doses and did not disturb its normal activity. Total LDH activity was inhibited in the presence of both complexes, but Ru(II) complexes showed different effects on the activity of LDH isoenzymes. The activities of LDH1 and LDH2 isoenzymes were decreased in all applied doses of the complex 2, while the activity of LDH2 reduced using complex 1 in the same doses. Results of the present study suggest the neuro- and cardio protective potential of oral administration of complexes 1 and 2, as non-toxic compounds under physiological conditions. These protective effects are the result of their potent antioxidant activity.
AB  - Cilj ovog rada je da se ispitaju i uporede efekti dva kompleksa rutenijuma sa trifluoperazinom na aktivnost enzima acetilholinesteraze i laktat-dehidrogenase in vivo pod fiziološkim uslovima u krvi pacova. Kompleksi 1 i 2 pokazali su pozitivan efekat na aktivnost acetiholinesteraze u svim primenjenim dozama. Ukupna aktivnost LDH je inhibirana u prisustvu oba kompleksa, ali kompleksi Ru(II) pokazuju različite rezultate na izoenzimske oblike ovog enzima. Aktivnosti izoenzima LDH1 i LDH2 su smanjene u svim primenjenim dozama kompleksa 2, dok kompleks 1 smanjuje aktivnost samo izoenzima LDH2 u tim istim koncentracijama. Rezultati prikazanog istraživanja ukazuju na neuro - i kardio zaštitni potencijal oralne primene kompleksa 1 i 2, kao netoksičnih jedinjenja pod fiziološkim uslovima, indukovano preko njihovog snažnog antioksidativnog efekta.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta Veterinaria-Beograd
T1  - In vivo enzymes activities of some Ru(II) compounds with N-alkylphenothiazines
T1  - In vivo ispitivanje enzimske aktivnosti nekih Ru(II) jedinjenja sa N-alkilfenotiazinima
VL  - 66
IS  - 4
SP  - 497
EP  - 508
DO  - 10.1515/acve-2016-0043
ER  - 

@article{
author = "Krstić, Milena and Borozan, Sunčica and Sovilj, Sofija P. and Grgurić-Šipka, Sanja and Poljarević, Jelena",
year = "2016",
abstract = "The purpose of the present study was to investigate and compare the effects of two ruthenium complexes with trifluoperazine on acethylcholinesterase enzyme activity and lactate dehydrogenase levels in vivo under physiological conditions in rats blood. Complexes 1 and 2 showed positive effects on acethylcholinesterase at all doses and did not disturb its normal activity. Total LDH activity was inhibited in the presence of both complexes, but Ru(II) complexes showed different effects on the activity of LDH isoenzymes. The activities of LDH1 and LDH2 isoenzymes were decreased in all applied doses of the complex 2, while the activity of LDH2 reduced using complex 1 in the same doses. Results of the present study suggest the neuro- and cardio protective potential of oral administration of complexes 1 and 2, as non-toxic compounds under physiological conditions. These protective effects are the result of their potent antioxidant activity., Cilj ovog rada je da se ispitaju i uporede efekti dva kompleksa rutenijuma sa trifluoperazinom na aktivnost enzima acetilholinesteraze i laktat-dehidrogenase in vivo pod fiziološkim uslovima u krvi pacova. Kompleksi 1 i 2 pokazali su pozitivan efekat na aktivnost acetiholinesteraze u svim primenjenim dozama. Ukupna aktivnost LDH je inhibirana u prisustvu oba kompleksa, ali kompleksi Ru(II) pokazuju različite rezultate na izoenzimske oblike ovog enzima. Aktivnosti izoenzima LDH1 i LDH2 su smanjene u svim primenjenim dozama kompleksa 2, dok kompleks 1 smanjuje aktivnost samo izoenzima LDH2 u tim istim koncentracijama. Rezultati prikazanog istraživanja ukazuju na neuro - i kardio zaštitni potencijal oralne primene kompleksa 1 i 2, kao netoksičnih jedinjenja pod fiziološkim uslovima, indukovano preko njihovog snažnog antioksidativnog efekta.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta Veterinaria-Beograd",
title = "In vivo enzymes activities of some Ru(II) compounds with N-alkylphenothiazines, In vivo ispitivanje enzimske aktivnosti nekih Ru(II) jedinjenja sa N-alkilfenotiazinima",
volume = "66",
number = "4",
pages = "497-508",
doi = "10.1515/acve-2016-0043"
}

Krstić, M., Borozan, S., Sovilj, S. P., Grgurić-Šipka, S.,& Poljarević, J.. (2016). In vivo enzymes activities of some Ru(II) compounds with N-alkylphenothiazines. in Acta Veterinaria-Beograd
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 66(4), 497-508.
https://doi.org/10.1515/acve-2016-0043

Krstić M, Borozan S, Sovilj SP, Grgurić-Šipka S, Poljarević J. In vivo enzymes activities of some Ru(II) compounds with N-alkylphenothiazines. in Acta Veterinaria-Beograd. 2016;66(4):497-508.
doi:10.1515/acve-2016-0043 .

Krstić, Milena, Borozan, Sunčica, Sovilj, Sofija P., Grgurić-Šipka, Sanja, Poljarević, Jelena, "In vivo enzymes activities of some Ru(II) compounds with N-alkylphenothiazines" in Acta Veterinaria-Beograd, 66, no. 4 (2016):497-508,
https://doi.org/10.1515/acve-2016-0043 . .

TY  - JOUR
AU  - Krstić, Milena
AU  - Sovilj, Sofija P.
AU  - Borozan, Sunčica
AU  - Rancić, Milica
AU  - Poljarević, Jelena
AU  - Grgurić-Šipka, Sanja
PY  - 2016
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/1424
AB  - Phenothiazines are a large group of heterocyclic, aromatic molecules with nitrogen and sulphur between two benzene rings. Their derivatives, N-alkylphenothiazines have substituent on heterocyclic nitrogen atom which gives them different properties. Also, a series of these molecules have substitution on carbon atom at place 2 of phenothiazine benzene ring. Alkylphenothiazines contain aminoalkyl substituent and their alkyl, acyl and sulphonil derivatives, as well as monocyclic and bicyclic heterocycles attached at thiazine nitrogen atom or directly linked to benzene ring. The N-alkylphenothiazines have been known as antipsychotic drugs, but they also possess antibacterial, antifungal, anticancer activity, and ability to react with macromolecules and to coordinate to the metals. Metal complexes with N-alkylphenothiazines are biological active compounds with different antimicrobial activities and cytotoxic effect against tumor cell lines. The large field of application of N-alkylphenothiazines is very attractive in terms of synthesis of new related derivatives, metal complexes, studying their properties and applications. This article presents a review of the literature and a contemporary view at N-alkylphenothiazines - their synthesis and application, as well as their metal complexes which have promising biological effects.
PB  - Savez hemijskih inženjera, Beograd
T2  - Hemijska Industrija
T1  - N-alkylphenothiazines - synthesis, structure and application as ligands in metal complexes
VL  - 70
IS  - 4
SP  - 461
EP  - 471
DO  - 10.2298/HEMIND150331052K
ER  - 

@article{
author = "Krstić, Milena and Sovilj, Sofija P. and Borozan, Sunčica and Rancić, Milica and Poljarević, Jelena and Grgurić-Šipka, Sanja",
year = "2016",
abstract = "Phenothiazines are a large group of heterocyclic, aromatic molecules with nitrogen and sulphur between two benzene rings. Their derivatives, N-alkylphenothiazines have substituent on heterocyclic nitrogen atom which gives them different properties. Also, a series of these molecules have substitution on carbon atom at place 2 of phenothiazine benzene ring. Alkylphenothiazines contain aminoalkyl substituent and their alkyl, acyl and sulphonil derivatives, as well as monocyclic and bicyclic heterocycles attached at thiazine nitrogen atom or directly linked to benzene ring. The N-alkylphenothiazines have been known as antipsychotic drugs, but they also possess antibacterial, antifungal, anticancer activity, and ability to react with macromolecules and to coordinate to the metals. Metal complexes with N-alkylphenothiazines are biological active compounds with different antimicrobial activities and cytotoxic effect against tumor cell lines. The large field of application of N-alkylphenothiazines is very attractive in terms of synthesis of new related derivatives, metal complexes, studying their properties and applications. This article presents a review of the literature and a contemporary view at N-alkylphenothiazines - their synthesis and application, as well as their metal complexes which have promising biological effects.",
publisher = "Savez hemijskih inženjera, Beograd",
journal = "Hemijska Industrija",
title = "N-alkylphenothiazines - synthesis, structure and application as ligands in metal complexes",
volume = "70",
number = "4",
pages = "461-471",
doi = "10.2298/HEMIND150331052K"
}

Krstić, M., Sovilj, S. P., Borozan, S., Rancić, M., Poljarević, J.,& Grgurić-Šipka, S.. (2016). N-alkylphenothiazines - synthesis, structure and application as ligands in metal complexes. in Hemijska Industrija
Savez hemijskih inženjera, Beograd., 70(4), 461-471.
https://doi.org/10.2298/HEMIND150331052K

Krstić M, Sovilj SP, Borozan S, Rancić M, Poljarević J, Grgurić-Šipka S. N-alkylphenothiazines - synthesis, structure and application as ligands in metal complexes. in Hemijska Industrija. 2016;70(4):461-471.
doi:10.2298/HEMIND150331052K .

Krstić, Milena, Sovilj, Sofija P., Borozan, Sunčica, Rancić, Milica, Poljarević, Jelena, Grgurić-Šipka, Sanja, "N-alkylphenothiazines - synthesis, structure and application as ligands in metal complexes" in Hemijska Industrija, 70, no. 4 (2016):461-471,
https://doi.org/10.2298/HEMIND150331052K . .

TY  - JOUR
AU  - Poljarević, Jelena
AU  - Krstić, Milena
AU  - Grgurić-Šipka, Sanja
AU  - Sovilj, Sofija P.
AU  - Mišić, Dušan
AU  - Sabo, Tibor J.
PY  - 2013
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/989
AB  - Two new platinum(IV) complexes (1, trifluoperazinehydrochloride-aquapentachloridoplatinate(IV) and 2, chlorpromazine-chlorpromazinehydrochloridepentachloridoplatinate(IV)) were synthesized in the reaction of K-2[PtCl6] with trifluoperazine dihydrochloride (TF center dot 2HCl) or chlorpromazine hydrochloride (CP center dot HCl). The complexes were characterized by elemental analysis, molar conductivity measurement, and spectral (IR, H-1, C-13, 2D H-1-C-13 heteronuclear correlation spectra, Pt-195 NMR, and MS) methods. Outer-coordination sphere was proposed for 1; while in 2, the ligand was coordinated to the metal. The complexes exhibit antibacterial effect on strains of Bacillus subtilis, Bacillus cereus, Bacillus pumilus, and methicillin-resistant Staphylococci as Gram-positive bacteria and an Escherichia coli as Gram-negative bacteria, as well as the reference strains.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Journal of Coordination Chemistry
T1  - Platinum(IV) complexes with N-alkylphenothiazines: synthesis, characterization, and antibacterial activity
VL  - 66
IS  - 21
SP  - 3760
EP  - 3769
DO  - 10.1080/00958972.2013.851788
ER  - 

@article{
author = "Poljarević, Jelena and Krstić, Milena and Grgurić-Šipka, Sanja and Sovilj, Sofija P. and Mišić, Dušan and Sabo, Tibor J.",
year = "2013",
abstract = "Two new platinum(IV) complexes (1, trifluoperazinehydrochloride-aquapentachloridoplatinate(IV) and 2, chlorpromazine-chlorpromazinehydrochloridepentachloridoplatinate(IV)) were synthesized in the reaction of K-2[PtCl6] with trifluoperazine dihydrochloride (TF center dot 2HCl) or chlorpromazine hydrochloride (CP center dot HCl). The complexes were characterized by elemental analysis, molar conductivity measurement, and spectral (IR, H-1, C-13, 2D H-1-C-13 heteronuclear correlation spectra, Pt-195 NMR, and MS) methods. Outer-coordination sphere was proposed for 1; while in 2, the ligand was coordinated to the metal. The complexes exhibit antibacterial effect on strains of Bacillus subtilis, Bacillus cereus, Bacillus pumilus, and methicillin-resistant Staphylococci as Gram-positive bacteria and an Escherichia coli as Gram-negative bacteria, as well as the reference strains.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Journal of Coordination Chemistry",
title = "Platinum(IV) complexes with N-alkylphenothiazines: synthesis, characterization, and antibacterial activity",
volume = "66",
number = "21",
pages = "3760-3769",
doi = "10.1080/00958972.2013.851788"
}

Poljarević, J., Krstić, M., Grgurić-Šipka, S., Sovilj, S. P., Mišić, D.,& Sabo, T. J.. (2013). Platinum(IV) complexes with N-alkylphenothiazines: synthesis, characterization, and antibacterial activity. in Journal of Coordination Chemistry
Taylor & Francis Ltd, Abingdon., 66(21), 3760-3769.
https://doi.org/10.1080/00958972.2013.851788

Poljarević J, Krstić M, Grgurić-Šipka S, Sovilj SP, Mišić D, Sabo TJ. Platinum(IV) complexes with N-alkylphenothiazines: synthesis, characterization, and antibacterial activity. in Journal of Coordination Chemistry. 2013;66(21):3760-3769.
doi:10.1080/00958972.2013.851788 .

Poljarević, Jelena, Krstić, Milena, Grgurić-Šipka, Sanja, Sovilj, Sofija P., Mišić, Dušan, Sabo, Tibor J., "Platinum(IV) complexes with N-alkylphenothiazines: synthesis, characterization, and antibacterial activity" in Journal of Coordination Chemistry, 66, no. 21 (2013):3760-3769,
https://doi.org/10.1080/00958972.2013.851788 . .

TY  - JOUR
AU  - Krstić, Milena
AU  - Sovilj, Sofija P.
AU  - Grgurić-Šipka, Sanja
AU  - Radosavljevic-Evans, Ivana
AU  - Borozan, Sunčica
AU  - Santibanez, Juan Francisco
PY  - 2011
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/756
AB  - Three new ruthenium(II) complexes 1-3 containing N-alkylphenothiazine molecules were synthesized by reaction of [RuCl2(eta(6)-P-cymene)](2) with chlorpromazine hydrochloride (1), trifluoperazine dihydrochloride (2) or thioridazine hydrochloride (3). The compounds of the general formula L[RuCl3(eta(6)-p-cymene)] were characterized by elemental analysis and spectroscopic methods (FT-IR, UV-Vis, H-1 and C-13 NMR). Complex 2 was structurally characterized by single crystal X-ray diffraction. In vitro cytotoxic activity of complexes 1-3 were assayed in four human carcinoma cell lines MCF-7, MDA-MB-453 (breast carcinoma), SW-480 (colon carcinoma) and IM9 (myeloma multiple cells). The highest cytotoxicity (12.1 <= IC50 <= 17.3 mu M) and induced a total (SW-480) or almost total cell death (MCF-7. MDA-MB-453) at 25 mu M in 48 h of treatment were observed for complex 2. The influence of three different doses (0.4, 4.5 and 90.4 mu M/kg bw) of complex 2 on activities of antioxidants enzymes (superoxide dismutase (SOD) and catalase (CAT)) and lactate dehydrogenase (LDH) were investigated under physiological conditions. The effects on nitrite production (NO2-) and level of erythrocytes malondialdehyde (MDA) in rats blood were evaluated, too.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
T2  - European Journal of Medicinal Chemistry
T1  - Synthesis, structural and spectroscopic characterization, in vitro cytotoxicity and in vivo activity as free radical scavengers of chlorido(p-cymene) complexes of ruthenium(II) containing N-alkylphenothiazines
VL  - 46
IS  - 9
SP  - 4168
EP  - 4177
DO  - 10.1016/j.ejmech.2011.06.019
ER  - 

@article{
author = "Krstić, Milena and Sovilj, Sofija P. and Grgurić-Šipka, Sanja and Radosavljevic-Evans, Ivana and Borozan, Sunčica and Santibanez, Juan Francisco",
year = "2011",
abstract = "Three new ruthenium(II) complexes 1-3 containing N-alkylphenothiazine molecules were synthesized by reaction of [RuCl2(eta(6)-P-cymene)](2) with chlorpromazine hydrochloride (1), trifluoperazine dihydrochloride (2) or thioridazine hydrochloride (3). The compounds of the general formula L[RuCl3(eta(6)-p-cymene)] were characterized by elemental analysis and spectroscopic methods (FT-IR, UV-Vis, H-1 and C-13 NMR). Complex 2 was structurally characterized by single crystal X-ray diffraction. In vitro cytotoxic activity of complexes 1-3 were assayed in four human carcinoma cell lines MCF-7, MDA-MB-453 (breast carcinoma), SW-480 (colon carcinoma) and IM9 (myeloma multiple cells). The highest cytotoxicity (12.1 <= IC50 <= 17.3 mu M) and induced a total (SW-480) or almost total cell death (MCF-7. MDA-MB-453) at 25 mu M in 48 h of treatment were observed for complex 2. The influence of three different doses (0.4, 4.5 and 90.4 mu M/kg bw) of complex 2 on activities of antioxidants enzymes (superoxide dismutase (SOD) and catalase (CAT)) and lactate dehydrogenase (LDH) were investigated under physiological conditions. The effects on nitrite production (NO2-) and level of erythrocytes malondialdehyde (MDA) in rats blood were evaluated, too.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux",
journal = "European Journal of Medicinal Chemistry",
title = "Synthesis, structural and spectroscopic characterization, in vitro cytotoxicity and in vivo activity as free radical scavengers of chlorido(p-cymene) complexes of ruthenium(II) containing N-alkylphenothiazines",
volume = "46",
number = "9",
pages = "4168-4177",
doi = "10.1016/j.ejmech.2011.06.019"
}

Krstić, M., Sovilj, S. P., Grgurić-Šipka, S., Radosavljevic-Evans, I., Borozan, S.,& Santibanez, J. F.. (2011). Synthesis, structural and spectroscopic characterization, in vitro cytotoxicity and in vivo activity as free radical scavengers of chlorido(p-cymene) complexes of ruthenium(II) containing N-alkylphenothiazines. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux., 46(9), 4168-4177.
https://doi.org/10.1016/j.ejmech.2011.06.019

Krstić M, Sovilj SP, Grgurić-Šipka S, Radosavljevic-Evans I, Borozan S, Santibanez JF. Synthesis, structural and spectroscopic characterization, in vitro cytotoxicity and in vivo activity as free radical scavengers of chlorido(p-cymene) complexes of ruthenium(II) containing N-alkylphenothiazines. in European Journal of Medicinal Chemistry. 2011;46(9):4168-4177.
doi:10.1016/j.ejmech.2011.06.019 .

Krstić, Milena, Sovilj, Sofija P., Grgurić-Šipka, Sanja, Radosavljevic-Evans, Ivana, Borozan, Sunčica, Santibanez, Juan Francisco, "Synthesis, structural and spectroscopic characterization, in vitro cytotoxicity and in vivo activity as free radical scavengers of chlorido(p-cymene) complexes of ruthenium(II) containing N-alkylphenothiazines" in European Journal of Medicinal Chemistry, 46, no. 9 (2011):4168-4177,
https://doi.org/10.1016/j.ejmech.2011.06.019 . .

TY  - JOUR
AU  - Krstić, Milena
AU  - Sovilj, Sofija P.
AU  - Grgurić-Šipka, Sanja
AU  - Radosavljevic-Evans, Ivana
AU  - Borozan, Sunčica
AU  - Santibanez, Juan Francisco
AU  - Kocić, Jelena
PY  - 2010
UR  - https://vet-erinar.vet.bg.ac.rs/handle/123456789/710
AB  - Three new complexes of the general formula L[RuCl3(DMSO)(3)] (1-3), where L = chlorpromazine hydrochloride, trifluoroperazine dihydrochloride or thioridazine hydrochloride, were prepared and characterized by elemental analysis and spectroscopic methods (FT-IR, UV-Vis, H-1 NMR and C-13 NMR). In addition, the crystal structure of the complex 2 containing trifluoroperazine dihydrochloride was solved by single crystal X-ray diffraction. The complex crystallizes in the monoclinic system, space group P2(1)/n, with a = 10.4935(7) angstrom, b = 18.6836(12) angstrom, c = 19.9250(13) angstrom, beta = 98.448(2)degrees, V = 3864.0(4) angstrom(3). The structure was refined to the agreement factors of R = 4.79%, R-w = 11.23%. The effect of three different doses (0.4, 4.5 and 90.4 mu M/kg bw) of complex 2 on superoxide dismutase (SOD) and catalase (CAT) activity was investigated under physiological conditions. Influence on nitrite production (NO2-) and the level of erythrocytes malondialdehyde (MDA) in rats blood was also evaluated. Complex 2 did not affect the CAT enzyme activity in vivo and did not cause the hydroxyl radicals production. In the 0.4 and 4.5 mu M/kg bw doses it showed almost the same or lower SOD activity and nitrite levels, while the dose of 90.4 mu M/kg bw significantly increased these parameters. Finally, the cytotoxicity of complexes were assayed in four human carcinoma cell lines MCF-7, MDA-MB-453 (breast carcinoma), SW-480 (colon adenocarcinoma) and IM9 (myeloma multiple cells). Antiproliferative activity in vitro with low IC50 during 48 h of treatment was observed.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
T2  - European Journal of Medicinal Chemistry
T1  - New ruthenium(II) complexes with N-alkylphenothiazines: Synthesis, structure, in vivo activity as free radical scavengers and in vitro cytotoxicity
VL  - 45
IS  - 9
SP  - 3669
EP  - 3676
DO  - 10.1016/j.ejmech.2010.05.013
ER  - 

@article{
author = "Krstić, Milena and Sovilj, Sofija P. and Grgurić-Šipka, Sanja and Radosavljevic-Evans, Ivana and Borozan, Sunčica and Santibanez, Juan Francisco and Kocić, Jelena",
year = "2010",
abstract = "Three new complexes of the general formula L[RuCl3(DMSO)(3)] (1-3), where L = chlorpromazine hydrochloride, trifluoroperazine dihydrochloride or thioridazine hydrochloride, were prepared and characterized by elemental analysis and spectroscopic methods (FT-IR, UV-Vis, H-1 NMR and C-13 NMR). In addition, the crystal structure of the complex 2 containing trifluoroperazine dihydrochloride was solved by single crystal X-ray diffraction. The complex crystallizes in the monoclinic system, space group P2(1)/n, with a = 10.4935(7) angstrom, b = 18.6836(12) angstrom, c = 19.9250(13) angstrom, beta = 98.448(2)degrees, V = 3864.0(4) angstrom(3). The structure was refined to the agreement factors of R = 4.79%, R-w = 11.23%. The effect of three different doses (0.4, 4.5 and 90.4 mu M/kg bw) of complex 2 on superoxide dismutase (SOD) and catalase (CAT) activity was investigated under physiological conditions. Influence on nitrite production (NO2-) and the level of erythrocytes malondialdehyde (MDA) in rats blood was also evaluated. Complex 2 did not affect the CAT enzyme activity in vivo and did not cause the hydroxyl radicals production. In the 0.4 and 4.5 mu M/kg bw doses it showed almost the same or lower SOD activity and nitrite levels, while the dose of 90.4 mu M/kg bw significantly increased these parameters. Finally, the cytotoxicity of complexes were assayed in four human carcinoma cell lines MCF-7, MDA-MB-453 (breast carcinoma), SW-480 (colon adenocarcinoma) and IM9 (myeloma multiple cells). Antiproliferative activity in vitro with low IC50 during 48 h of treatment was observed.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux",
journal = "European Journal of Medicinal Chemistry",
title = "New ruthenium(II) complexes with N-alkylphenothiazines: Synthesis, structure, in vivo activity as free radical scavengers and in vitro cytotoxicity",
volume = "45",
number = "9",
pages = "3669-3676",
doi = "10.1016/j.ejmech.2010.05.013"
}

Krstić, M., Sovilj, S. P., Grgurić-Šipka, S., Radosavljevic-Evans, I., Borozan, S., Santibanez, J. F.,& Kocić, J.. (2010). New ruthenium(II) complexes with N-alkylphenothiazines: Synthesis, structure, in vivo activity as free radical scavengers and in vitro cytotoxicity. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux., 45(9), 3669-3676.
https://doi.org/10.1016/j.ejmech.2010.05.013

Krstić M, Sovilj SP, Grgurić-Šipka S, Radosavljevic-Evans I, Borozan S, Santibanez JF, Kocić J. New ruthenium(II) complexes with N-alkylphenothiazines: Synthesis, structure, in vivo activity as free radical scavengers and in vitro cytotoxicity. in European Journal of Medicinal Chemistry. 2010;45(9):3669-3676.
doi:10.1016/j.ejmech.2010.05.013 .

Krstić, Milena, Sovilj, Sofija P., Grgurić-Šipka, Sanja, Radosavljevic-Evans, Ivana, Borozan, Sunčica, Santibanez, Juan Francisco, Kocić, Jelena, "New ruthenium(II) complexes with N-alkylphenothiazines: Synthesis, structure, in vivo activity as free radical scavengers and in vitro cytotoxicity" in European Journal of Medicinal Chemistry, 45, no. 9 (2010):3669-3676,
https://doi.org/10.1016/j.ejmech.2010.05.013 . .