TY  - JOUR
AU  - Pantelić, Nebojša Đ.
AU  - Zmejkovski, Bojana
AU  - Kolundžija, Branka
AU  - Crnogorac, Marija Đorđić
AU  - Vujić, Jelena M.
AU  - Dojčinović, Biljana
AU  - Trifunović, Srećko R.
AU  - Stanojković, Tatjana
AU  - Sabo, Tibor
AU  - Kaluđerović, Goran N.
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2931
AB  - Four novel gold(III) complexes of general formulae [AuCl2{(S,S)-R(2)eddl}]PF6 (R(2)eddl = O,O'-dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoate, R= n-Pr, n-Bu, n-Pe, i-Bu; 1-4, respectively), were synthesized and characterized by elemental analysis, UV/Vis, IR, and NMR spectroscopy, as well as high resolution mass spectrometry. Density functional theory calculations pointed out that (R,R)-N,N'-configuration diastereoisomers were energetically the most favorable. Duo to high cytotoxic activity complex 3 was chosen for stability study in DMSO, no decomposition occurs within 24 h, and for the reaction with ascorbic acid in which was reduced immediately. Additionally, 3 interacts with bovine serum albumin (BSA) as proven by UV/Vis spectroscopy. In vitro antitumor activity was determined against human cervix adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human melanoma (Fem-x) cancer cell lines, as well as against non-cancerous human embryonic lung fibroblast cells MRC-5. The highest activity was observed against K562 cells (IC50: 5.04-6.51 mu M). Selectivity indices showed that these complexes are less toxic than cisplatin. 3 had a similar viability kinetics on HeLa cells as cisplatin. Drug accumulation studies in HeLa cells showed that the total gold uptake increased much faster than that of cisplatin pointing out that 3 more efficiently enters the cells than cisplatin. Furthermore, morphological and cell cycle analysis reveal that gold(III) complexes induced apoptosis in time- and dose-dependent manner.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N′-ethylenediamine bidentate ester ligands
VL  - 172
SP  - 55
EP  - 66
DO  - 10.1016/j.jinorgbio.2017.04.001
ER  - 

@article{
author = "Pantelić, Nebojša Đ. and Zmejkovski, Bojana and Kolundžija, Branka and Crnogorac, Marija Đorđić and Vujić, Jelena M. and Dojčinović, Biljana and Trifunović, Srećko R. and Stanojković, Tatjana and Sabo, Tibor and Kaluđerović, Goran N.",
year = "2017",
abstract = "Four novel gold(III) complexes of general formulae [AuCl2{(S,S)-R(2)eddl}]PF6 (R(2)eddl = O,O'-dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoate, R= n-Pr, n-Bu, n-Pe, i-Bu; 1-4, respectively), were synthesized and characterized by elemental analysis, UV/Vis, IR, and NMR spectroscopy, as well as high resolution mass spectrometry. Density functional theory calculations pointed out that (R,R)-N,N'-configuration diastereoisomers were energetically the most favorable. Duo to high cytotoxic activity complex 3 was chosen for stability study in DMSO, no decomposition occurs within 24 h, and for the reaction with ascorbic acid in which was reduced immediately. Additionally, 3 interacts with bovine serum albumin (BSA) as proven by UV/Vis spectroscopy. In vitro antitumor activity was determined against human cervix adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human melanoma (Fem-x) cancer cell lines, as well as against non-cancerous human embryonic lung fibroblast cells MRC-5. The highest activity was observed against K562 cells (IC50: 5.04-6.51 mu M). Selectivity indices showed that these complexes are less toxic than cisplatin. 3 had a similar viability kinetics on HeLa cells as cisplatin. Drug accumulation studies in HeLa cells showed that the total gold uptake increased much faster than that of cisplatin pointing out that 3 more efficiently enters the cells than cisplatin. Furthermore, morphological and cell cycle analysis reveal that gold(III) complexes induced apoptosis in time- and dose-dependent manner.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N′-ethylenediamine bidentate ester ligands",
volume = "172",
pages = "55-66",
doi = "10.1016/j.jinorgbio.2017.04.001"
}

Pantelić, N. Đ., Zmejkovski, B., Kolundžija, B., Crnogorac, M. Đ., Vujić, J. M., Dojčinović, B., Trifunović, S. R., Stanojković, T., Sabo, T.,& Kaluđerović, G. N.. (2017). In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N′-ethylenediamine bidentate ester ligands. in Journal of Inorganic Biochemistry
Elsevier., 172, 55-66.
https://doi.org/10.1016/j.jinorgbio.2017.04.001

Pantelić NĐ, Zmejkovski B, Kolundžija B, Crnogorac MĐ, Vujić JM, Dojčinović B, Trifunović SR, Stanojković T, Sabo T, Kaluđerović GN. In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N′-ethylenediamine bidentate ester ligands. in Journal of Inorganic Biochemistry. 2017;172:55-66.
doi:10.1016/j.jinorgbio.2017.04.001 .

Pantelić, Nebojša Đ., Zmejkovski, Bojana, Kolundžija, Branka, Crnogorac, Marija Đorđić, Vujić, Jelena M., Dojčinović, Biljana, Trifunović, Srećko R., Stanojković, Tatjana, Sabo, Tibor, Kaluđerović, Goran N., "In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N′-ethylenediamine bidentate ester ligands" in Journal of Inorganic Biochemistry, 172 (2017):55-66,
https://doi.org/10.1016/j.jinorgbio.2017.04.001 . .

TY  - JOUR
AU  - Juranić, Ivan
AU  - Tošić, Ana V.
AU  - Kolundžija, Branka
AU  - Drakulić, Branko
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2670
AB  - Antiproliferative activity of twenty one Michael adducts of aroylacrylic acids and cyclic amines (  N -Me-piperazine, imidazole, 2-Me-imidazole, and indole) was tested toward five human tumor cell lines (HeLa, LS174, K562, FemX, MDA-MB-361) in vitro. Compounds exerted antiproliferative activity in the high to the single-digit micromolar concentrations, causing increase of the cell population fraction in S phase and apoptosis.   N -Me-piperazine and imidazole derivatives of aroylacrylic acids substituted with bulky alkyl substituents (2,4-di-  i -Pr-Ph-, 2,4,6-tri-Et-Ph-, or   β -tetrahydronaphthyl-) showed the best potency, while indole adducts were proved as the inferior antiproliferative agents. Few compounds showed significant selectivity, tumor versus healthy cells, with selectivity index   ∼60  for the most selective congener. An unbiased in silico distinction between more and less potent compounds was obtained from 3D QSAR models derived by alignment-independent GRIND-2 descriptors.
PB  - Springer
T2  - Molecular Diversity
T1  - Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines
VL  - 18
IS  - 3
SP  - 577
EP  - 592
DO  - 10.1007/s11030-014-9528-4
ER  - 

@article{
author = "Juranić, Ivan and Tošić, Ana V. and Kolundžija, Branka and Drakulić, Branko",
year = "2014",
abstract = "Antiproliferative activity of twenty one Michael adducts of aroylacrylic acids and cyclic amines (  N -Me-piperazine, imidazole, 2-Me-imidazole, and indole) was tested toward five human tumor cell lines (HeLa, LS174, K562, FemX, MDA-MB-361) in vitro. Compounds exerted antiproliferative activity in the high to the single-digit micromolar concentrations, causing increase of the cell population fraction in S phase and apoptosis.   N -Me-piperazine and imidazole derivatives of aroylacrylic acids substituted with bulky alkyl substituents (2,4-di-  i -Pr-Ph-, 2,4,6-tri-Et-Ph-, or   β -tetrahydronaphthyl-) showed the best potency, while indole adducts were proved as the inferior antiproliferative agents. Few compounds showed significant selectivity, tumor versus healthy cells, with selectivity index   ∼60  for the most selective congener. An unbiased in silico distinction between more and less potent compounds was obtained from 3D QSAR models derived by alignment-independent GRIND-2 descriptors.",
publisher = "Springer",
journal = "Molecular Diversity",
title = "Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines",
volume = "18",
number = "3",
pages = "577-592",
doi = "10.1007/s11030-014-9528-4"
}

Juranić, I., Tošić, A. V., Kolundžija, B.,& Drakulić, B.. (2014). Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines. in Molecular Diversity
Springer., 18(3), 577-592.
https://doi.org/10.1007/s11030-014-9528-4

Juranić I, Tošić AV, Kolundžija B, Drakulić B. Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines. in Molecular Diversity. 2014;18(3):577-592.
doi:10.1007/s11030-014-9528-4 .

Juranić, Ivan, Tošić, Ana V., Kolundžija, Branka, Drakulić, Branko, "Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines" in Molecular Diversity, 18, no. 3 (2014):577-592,
https://doi.org/10.1007/s11030-014-9528-4 . .

TY  - JOUR
AU  - Vitorović-Todorović, Maja D.
AU  - Erić-Nikolić, Aleksandra
AU  - Kolundžija, Branka
AU  - Hamel, Ernest
AU  - Ristić, Slavica S.
AU  - Juranić, Ivan
AU  - Drakulić, Branko
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2873
AB  - Antiproliferative activity of twenty-nine (E)-4-aryl-4-oxo-2-butenoic acid amides against three human
tumor cell lines (HeLa, FemX, and K562) is reported. Compounds showed antiproliferative activity in
one-digit micromolar to submicromolar concentrations. The most active derivatives toward all the cell
lines tested bear alkyl substituents on the aroyl moiety of the molecules. Fourteen compounds showed
tubulin assembly inhibition at concentrations <20 mM. The most potent inhibitor of tubulin assembly
was unsubstituted compound 1, with IC50 ¼ 2.9 mM. Compound 23 had an oral LD50 in vivo of 45 mg/kg in
mice. Cell cycle analysis on K562 cells showed that compounds 1, 2 and 23 caused accumulation of cells
in the G2/M phase, but inhibition of microtubule polymerization is not the principal mode of action of
the compounds. Nevertheless, they may be useful leads for the design of a new class of antitubulin
agents.
PB  - Elsevier Masson SAS.
T2  - European Journal of Medicinal Chemistry
T1  - (E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization
VL  - 62
SP  - 40
EP  - 50
DO  - 10.1016/j.ejmech.2013.01.006
ER  - 

@article{
author = "Vitorović-Todorović, Maja D. and Erić-Nikolić, Aleksandra and Kolundžija, Branka and Hamel, Ernest and Ristić, Slavica S. and Juranić, Ivan and Drakulić, Branko",
year = "2013",
abstract = "Antiproliferative activity of twenty-nine (E)-4-aryl-4-oxo-2-butenoic acid amides against three human
tumor cell lines (HeLa, FemX, and K562) is reported. Compounds showed antiproliferative activity in
one-digit micromolar to submicromolar concentrations. The most active derivatives toward all the cell
lines tested bear alkyl substituents on the aroyl moiety of the molecules. Fourteen compounds showed
tubulin assembly inhibition at concentrations <20 mM. The most potent inhibitor of tubulin assembly
was unsubstituted compound 1, with IC50 ¼ 2.9 mM. Compound 23 had an oral LD50 in vivo of 45 mg/kg in
mice. Cell cycle analysis on K562 cells showed that compounds 1, 2 and 23 caused accumulation of cells
in the G2/M phase, but inhibition of microtubule polymerization is not the principal mode of action of
the compounds. Nevertheless, they may be useful leads for the design of a new class of antitubulin
agents.",
publisher = "Elsevier Masson SAS.",
journal = "European Journal of Medicinal Chemistry",
title = "(E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization",
volume = "62",
pages = "40-50",
doi = "10.1016/j.ejmech.2013.01.006"
}

Vitorović-Todorović, M. D., Erić-Nikolić, A., Kolundžija, B., Hamel, E., Ristić, S. S., Juranić, I.,& Drakulić, B.. (2013). (E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization. in European Journal of Medicinal Chemistry
Elsevier Masson SAS.., 62, 40-50.
https://doi.org/10.1016/j.ejmech.2013.01.006

Vitorović-Todorović MD, Erić-Nikolić A, Kolundžija B, Hamel E, Ristić SS, Juranić I, Drakulić B. (E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization. in European Journal of Medicinal Chemistry. 2013;62:40-50.
doi:10.1016/j.ejmech.2013.01.006 .

Vitorović-Todorović, Maja D., Erić-Nikolić, Aleksandra, Kolundžija, Branka, Hamel, Ernest, Ristić, Slavica S., Juranić, Ivan, Drakulić, Branko, "(E)-4-Aryl-4-oxo-2-butenoic acid amides, chalconeearoylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization" in European Journal of Medicinal Chemistry, 62 (2013):40-50,
https://doi.org/10.1016/j.ejmech.2013.01.006 . .