TY  - JOUR
AU  - Jakovljević, Katarina
AU  - Joksović, Milan D.
AU  - Matić, Ivana Z.
AU  - Petrović, Nina
AU  - Stanojković, Tatjana P.
AU  - Sladić, Dušan M.
AU  - Vujčić, Miroslava T.
AU  - Janović, Barbara S.
AU  - Joksović, Ljubinka G.
AU  - Trifunović, Snežana
AU  - Marković, Violeta
PY  - 2018
UR  - http://xlink.rsc.org/?DOI=C8MD00316E
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7928
AB  - Hybrid compounds that combine the 1,3,4-thiadiazole-containing catechol moiety with a chalcone motif were synthesized and examined for their antioxidant activity, cytotoxicity, and DNA-binding activity. A series of thirteen compounds showed strong antioxidant and cytotoxic effects on human acute promyelocytic leukemia HL-60 cells. Several compounds exerted good cytotoxic activities on cervical adenocarcinoma HeLa cells. The treatment of HeLa cells with IC50 and double IC50 concentrations of the compounds 5a, 5c, 5f, and 5m induced a statistically significant increase in the percentage of cells within a subG1 cell cycle phase. The examined compounds caused G2/M cell cycle arrest in HeLa cells. Each of these compounds triggered apoptosis in HeLa cells through activation of caspase-3, the main effector caspase, caspase-8, which is involved in the extrinsic apoptotic pathway, and caspase-9, which is involved in the intrinsic apoptotic pathway. All of the examined compounds decreased the expression levels of MMP2 in HeLa cells and levels of protumorigenic miR-133b. Compounds 5a and 5m lowered the expression level of oncogenic miR-21 in HeLa cells. In addition, compounds 5a, 5f, and 5m decreased the expression levels of oncogenic miR-155 while the treatment of HeLa cells with compounds 5a, 5c, and 5f increased expression of tumor-suppressive miR-206. Observed effects of these compounds on expression levels of four examined miRNAs suggest their prominent cancer-suppressive activity. An investigation by absorption and fluorescence spectroscopy showed more efficient calf thymus DNA binding activity of the compound 5m in comparison to other tested compounds. Results of a pUC19 plasmid cleavage study and comet assay showed DNA damaging activities of compounds 5a and 5c.
T2  - MedChemComm
T1  - Novel 1,3,4-thiadiazole–chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies
VL  - 9
IS  - 10
SP  - 1679
EP  - 1697
DO  - 10.1039/C8MD00316E
ER  - 

@article{
author = "Jakovljević, Katarina and Joksović, Milan D. and Matić, Ivana Z. and Petrović, Nina and Stanojković, Tatjana P. and Sladić, Dušan M. and Vujčić, Miroslava T. and Janović, Barbara S. and Joksović, Ljubinka G. and Trifunović, Snežana and Marković, Violeta",
year = "2018",
abstract = "Hybrid compounds that combine the 1,3,4-thiadiazole-containing catechol moiety with a chalcone motif were synthesized and examined for their antioxidant activity, cytotoxicity, and DNA-binding activity. A series of thirteen compounds showed strong antioxidant and cytotoxic effects on human acute promyelocytic leukemia HL-60 cells. Several compounds exerted good cytotoxic activities on cervical adenocarcinoma HeLa cells. The treatment of HeLa cells with IC50 and double IC50 concentrations of the compounds 5a, 5c, 5f, and 5m induced a statistically significant increase in the percentage of cells within a subG1 cell cycle phase. The examined compounds caused G2/M cell cycle arrest in HeLa cells. Each of these compounds triggered apoptosis in HeLa cells through activation of caspase-3, the main effector caspase, caspase-8, which is involved in the extrinsic apoptotic pathway, and caspase-9, which is involved in the intrinsic apoptotic pathway. All of the examined compounds decreased the expression levels of MMP2 in HeLa cells and levels of protumorigenic miR-133b. Compounds 5a and 5m lowered the expression level of oncogenic miR-21 in HeLa cells. In addition, compounds 5a, 5f, and 5m decreased the expression levels of oncogenic miR-155 while the treatment of HeLa cells with compounds 5a, 5c, and 5f increased expression of tumor-suppressive miR-206. Observed effects of these compounds on expression levels of four examined miRNAs suggest their prominent cancer-suppressive activity. An investigation by absorption and fluorescence spectroscopy showed more efficient calf thymus DNA binding activity of the compound 5m in comparison to other tested compounds. Results of a pUC19 plasmid cleavage study and comet assay showed DNA damaging activities of compounds 5a and 5c.",
journal = "MedChemComm",
title = "Novel 1,3,4-thiadiazole–chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies",
volume = "9",
number = "10",
pages = "1679-1697",
doi = "10.1039/C8MD00316E"
}

Jakovljević, K., Joksović, M. D., Matić, I. Z., Petrović, N., Stanojković, T. P., Sladić, D. M., Vujčić, M. T., Janović, B. S., Joksović, L. G., Trifunović, S.,& Marković, V.. (2018). Novel 1,3,4-thiadiazole–chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies. in MedChemComm, 9(10), 1679-1697.
https://doi.org/10.1039/C8MD00316E

Jakovljević K, Joksović MD, Matić IZ, Petrović N, Stanojković TP, Sladić DM, Vujčić MT, Janović BS, Joksović LG, Trifunović S, Marković V. Novel 1,3,4-thiadiazole–chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies. in MedChemComm. 2018;9(10):1679-1697.
doi:10.1039/C8MD00316E .

Jakovljević, Katarina, Joksović, Milan D., Matić, Ivana Z., Petrović, Nina, Stanojković, Tatjana P., Sladić, Dušan M., Vujčić, Miroslava T., Janović, Barbara S., Joksović, Ljubinka G., Trifunović, Snežana, Marković, Violeta, "Novel 1,3,4-thiadiazole–chalcone hybrids containing catechol moiety: synthesis, antioxidant activity, cytotoxicity and DNA interaction studies" in MedChemComm, 9, no. 10 (2018):1679-1697,
https://doi.org/10.1039/C8MD00316E . .

TY  - JOUR
AU  - Filipović, Nenad R.
AU  - Bjelogrlić, Snežana
AU  - Todorović, Tamara R.
AU  - Blagojević, Vladimir A.
AU  - Muller, Christian D.
AU  - Marinković, Aleksandar D.
AU  - Vujčić, Miroslava T.
AU  - Janović, Barbara S.
AU  - Malešević, Aleksandar S.
AU  - Begović, Nebojša
AU  - Senćanski, Milan V.
AU  - Minić, Dragica M.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1331
AB  - A new Ni(II) complex, [Ni(L)(H2O)] (1), with diethyl 3,3-(2,2-(1,1-(pyridine-2,6-diyl) bis(ethan-1-yl-1-ylidene)) bis(hydrazin-1-yl-2-ylidene)) bis(3-oxopropanoate) ligand (H2L) was synthesized as a potential chemotherapeutic agent. Polidentate ligand was coordinated to Ni(II) NNN-tridentately, in dianionic form, while monodentate water coordination completed square-planar geometry around metal. Structure in the solution was determined by NMR spectroscopy and the same coordination mode was observed in the solid state using IR spectroscopy and further verified by DFT calculations and electrochemical studies. Thermal stability of 1 was determined in both air and nitrogen atmosphere. Anticancer activity of 1 was investigated on acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma (AsPC-1) cell lines. On THP-1 cells 1 induced powerful apoptotic response (ED50 = 10 +/- 3 mu M), which was revealed to be only partially caspase-dependent, with activation of caspase-8 as the dominant course. This suggested that experimentally validated covalent binding of 1 to DNA is not the only mechanism responsible for programmed cell death. This was supported with experiments on AsPC-1 cells. Although treatment of those cells with 1 resulted in poor apoptotic response, cell cycle changes showed concentration-dependent shifts indicating a dual mechanism of activity. This study also reviews the results of preliminary biological screening, which demonstrates that 1 displays a unique pattern of anticancer activity with at least two mechanisms involved.
T2  - RSC Advances
T1  - Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines
VL  - 6
IS  - 110
SP  - 108726
EP  - 108740
DO  - 10.1039/c6ra24604d
ER  - 

@article{
author = "Filipović, Nenad R. and Bjelogrlić, Snežana and Todorović, Tamara R. and Blagojević, Vladimir A. and Muller, Christian D. and Marinković, Aleksandar D. and Vujčić, Miroslava T. and Janović, Barbara S. and Malešević, Aleksandar S. and Begović, Nebojša and Senćanski, Milan V. and Minić, Dragica M.",
year = "2016",
abstract = "A new Ni(II) complex, [Ni(L)(H2O)] (1), with diethyl 3,3-(2,2-(1,1-(pyridine-2,6-diyl) bis(ethan-1-yl-1-ylidene)) bis(hydrazin-1-yl-2-ylidene)) bis(3-oxopropanoate) ligand (H2L) was synthesized as a potential chemotherapeutic agent. Polidentate ligand was coordinated to Ni(II) NNN-tridentately, in dianionic form, while monodentate water coordination completed square-planar geometry around metal. Structure in the solution was determined by NMR spectroscopy and the same coordination mode was observed in the solid state using IR spectroscopy and further verified by DFT calculations and electrochemical studies. Thermal stability of 1 was determined in both air and nitrogen atmosphere. Anticancer activity of 1 was investigated on acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma (AsPC-1) cell lines. On THP-1 cells 1 induced powerful apoptotic response (ED50 = 10 +/- 3 mu M), which was revealed to be only partially caspase-dependent, with activation of caspase-8 as the dominant course. This suggested that experimentally validated covalent binding of 1 to DNA is not the only mechanism responsible for programmed cell death. This was supported with experiments on AsPC-1 cells. Although treatment of those cells with 1 resulted in poor apoptotic response, cell cycle changes showed concentration-dependent shifts indicating a dual mechanism of activity. This study also reviews the results of preliminary biological screening, which demonstrates that 1 displays a unique pattern of anticancer activity with at least two mechanisms involved.",
journal = "RSC Advances",
title = "Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines",
volume = "6",
number = "110",
pages = "108726-108740",
doi = "10.1039/c6ra24604d"
}

Filipović, N. R., Bjelogrlić, S., Todorović, T. R., Blagojević, V. A., Muller, C. D., Marinković, A. D., Vujčić, M. T., Janović, B. S., Malešević, A. S., Begović, N., Senćanski, M. V.,& Minić, D. M.. (2016). Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines. in RSC Advances, 6(110), 108726-108740.
https://doi.org/10.1039/c6ra24604d

Filipović NR, Bjelogrlić S, Todorović TR, Blagojević VA, Muller CD, Marinković AD, Vujčić MT, Janović BS, Malešević AS, Begović N, Senćanski MV, Minić DM. Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines. in RSC Advances. 2016;6(110):108726-108740.
doi:10.1039/c6ra24604d .

Filipović, Nenad R., Bjelogrlić, Snežana, Todorović, Tamara R., Blagojević, Vladimir A., Muller, Christian D., Marinković, Aleksandar D., Vujčić, Miroslava T., Janović, Barbara S., Malešević, Aleksandar S., Begović, Nebojša, Senćanski, Milan V., Minić, Dragica M., "Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines" in RSC Advances, 6, no. 110 (2016):108726-108740,
https://doi.org/10.1039/c6ra24604d . .