TY  - JOUR
AU  - Petronijević, Jelena
AU  - Bugarčič, Zorica M.
AU  - Bogdanović, Goran A.
AU  - Stefanović, Srđan
AU  - Janković, Nenad
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1444
AB  - Innovative, efficient, clean, experimentally simple and environmentally friendly one-pot biocatalytic synthesis of two small libraries of 3,4-dihydro-2(1H)-quinoxalinones (4a-m) and 3,4-dihydro-1,4-benzoxazin-2-ones (5a, 5b, 5f and 5k-o) by heterocyclization of ethyl 2-hydroxy-4-alkyl(aryl)-4-oxo-2-butenoates (1a-o) or their corresponding salts (1a-o) with o-phenylenediamine (2) or o-aminophenol (3) in lemon juice as a solvent and a catalyst is presented. In all reactions where esters 1a-o are used for 24 h, very good-to-excellent yields were achieved, but the best yield was realized in the synthesis of 5a (97%) from 3 and 1a. The use of enolate salts (1a-o) instead of the corresponding esters 1a-o significantly reduced the reaction time (up to 6 h) and good-to-excellent yields were achieved. Groups with electron-donating or -withdrawing effects at the aromatic ring of the ester did not have significant influences on the yield of targeted products. In addition, several selected 3,4-dihydro-2(1H)-quinoxalinones and 3,4dihydro-1,4-benzoxazin-2-ones on a gram-scale in the yields up to 92% were synthesized. The presented synthetic strategy has produced smaller amount of waste without by-products and with excellent values of green chemistry metrics (atom efficiency, reaction mass efficiency, E-factor and EcoScale).
T2  - Green Chemistry
T1  - An enolate ion as a synthon in biocatalytic synthesis of 3,4-dihydro-2(1H)-quinoxalinones and 3,4-dihydro-1,4-benzoxazin-2-ones: lemon juice as an alternative to hazardous solvents and catalysts
VL  - 19
IS  - 3
SP  - 707
EP  - 715
DO  - 10.1039/c6gc02893d
ER  - 

@article{
author = "Petronijević, Jelena and Bugarčič, Zorica M. and Bogdanović, Goran A. and Stefanović, Srđan and Janković, Nenad",
year = "2017",
abstract = "Innovative, efficient, clean, experimentally simple and environmentally friendly one-pot biocatalytic synthesis of two small libraries of 3,4-dihydro-2(1H)-quinoxalinones (4a-m) and 3,4-dihydro-1,4-benzoxazin-2-ones (5a, 5b, 5f and 5k-o) by heterocyclization of ethyl 2-hydroxy-4-alkyl(aryl)-4-oxo-2-butenoates (1a-o) or their corresponding salts (1a-o) with o-phenylenediamine (2) or o-aminophenol (3) in lemon juice as a solvent and a catalyst is presented. In all reactions where esters 1a-o are used for 24 h, very good-to-excellent yields were achieved, but the best yield was realized in the synthesis of 5a (97%) from 3 and 1a. The use of enolate salts (1a-o) instead of the corresponding esters 1a-o significantly reduced the reaction time (up to 6 h) and good-to-excellent yields were achieved. Groups with electron-donating or -withdrawing effects at the aromatic ring of the ester did not have significant influences on the yield of targeted products. In addition, several selected 3,4-dihydro-2(1H)-quinoxalinones and 3,4dihydro-1,4-benzoxazin-2-ones on a gram-scale in the yields up to 92% were synthesized. The presented synthetic strategy has produced smaller amount of waste without by-products and with excellent values of green chemistry metrics (atom efficiency, reaction mass efficiency, E-factor and EcoScale).",
journal = "Green Chemistry",
title = "An enolate ion as a synthon in biocatalytic synthesis of 3,4-dihydro-2(1H)-quinoxalinones and 3,4-dihydro-1,4-benzoxazin-2-ones: lemon juice as an alternative to hazardous solvents and catalysts",
volume = "19",
number = "3",
pages = "707-715",
doi = "10.1039/c6gc02893d"
}

Petronijević, J., Bugarčič, Z. M., Bogdanović, G. A., Stefanović, S.,& Janković, N.. (2017). An enolate ion as a synthon in biocatalytic synthesis of 3,4-dihydro-2(1H)-quinoxalinones and 3,4-dihydro-1,4-benzoxazin-2-ones: lemon juice as an alternative to hazardous solvents and catalysts. in Green Chemistry, 19(3), 707-715.
https://doi.org/10.1039/c6gc02893d

Petronijević J, Bugarčič ZM, Bogdanović GA, Stefanović S, Janković N. An enolate ion as a synthon in biocatalytic synthesis of 3,4-dihydro-2(1H)-quinoxalinones and 3,4-dihydro-1,4-benzoxazin-2-ones: lemon juice as an alternative to hazardous solvents and catalysts. in Green Chemistry. 2017;19(3):707-715.
doi:10.1039/c6gc02893d .

Petronijević, Jelena, Bugarčič, Zorica M., Bogdanović, Goran A., Stefanović, Srđan, Janković, Nenad, "An enolate ion as a synthon in biocatalytic synthesis of 3,4-dihydro-2(1H)-quinoxalinones and 3,4-dihydro-1,4-benzoxazin-2-ones: lemon juice as an alternative to hazardous solvents and catalysts" in Green Chemistry, 19, no. 3 (2017):707-715,
https://doi.org/10.1039/c6gc02893d . .

TY  - JOUR
AU  - Muškinja, Jovana
AU  - Janković, Nenad
AU  - Ratković, Zoran R.
AU  - Bogdanović, Goran A.
AU  - Bugarčič, Zorica M.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1163
AB  - A small library of novel 2-oxo-1,2,3,4-tetrahydropyrimidines was synthesized via a one-pot multicomponent Biginelli reaction. Copper complex which was used for the first time as a homogeneous and heterogeneous catalyst, makes this a facile and efficient reaction at room temperature. All the obtained products fall out of the solution in pure form and are easily isolated via filtration in good-to-excellent yields. The molecular structure of one of the products, ethyl 6-methyl-2-oxo-4-(4-isopropoxy-3-methoxyphenyl) - 1,2,3,4 - tetrahydropyrimidine-5- carboxylate, has been determined by X-ray crystallography. All non-hydrogen atoms in the heterocyclic, six-membered ring are determined to be approximately coplanar.
T2  - Molecular Diversity
T1  - Vanillic aldehydes for the one-pot synthesis of novel 2-oxo-1,2,3,4-tetrahydropyrimidines
VL  - 20
IS  - 3
SP  - 591
EP  - 604
DO  - 10.1007/s11030-016-9658-y
ER  - 

@article{
author = "Muškinja, Jovana and Janković, Nenad and Ratković, Zoran R. and Bogdanović, Goran A. and Bugarčič, Zorica M.",
year = "2016",
abstract = "A small library of novel 2-oxo-1,2,3,4-tetrahydropyrimidines was synthesized via a one-pot multicomponent Biginelli reaction. Copper complex which was used for the first time as a homogeneous and heterogeneous catalyst, makes this a facile and efficient reaction at room temperature. All the obtained products fall out of the solution in pure form and are easily isolated via filtration in good-to-excellent yields. The molecular structure of one of the products, ethyl 6-methyl-2-oxo-4-(4-isopropoxy-3-methoxyphenyl) - 1,2,3,4 - tetrahydropyrimidine-5- carboxylate, has been determined by X-ray crystallography. All non-hydrogen atoms in the heterocyclic, six-membered ring are determined to be approximately coplanar.",
journal = "Molecular Diversity",
title = "Vanillic aldehydes for the one-pot synthesis of novel 2-oxo-1,2,3,4-tetrahydropyrimidines",
volume = "20",
number = "3",
pages = "591-604",
doi = "10.1007/s11030-016-9658-y"
}

Muškinja, J., Janković, N., Ratković, Z. R., Bogdanović, G. A.,& Bugarčič, Z. M.. (2016). Vanillic aldehydes for the one-pot synthesis of novel 2-oxo-1,2,3,4-tetrahydropyrimidines. in Molecular Diversity, 20(3), 591-604.
https://doi.org/10.1007/s11030-016-9658-y

Muškinja J, Janković N, Ratković ZR, Bogdanović GA, Bugarčič ZM. Vanillic aldehydes for the one-pot synthesis of novel 2-oxo-1,2,3,4-tetrahydropyrimidines. in Molecular Diversity. 2016;20(3):591-604.
doi:10.1007/s11030-016-9658-y .

Muškinja, Jovana, Janković, Nenad, Ratković, Zoran R., Bogdanović, Goran A., Bugarčič, Zorica M., "Vanillic aldehydes for the one-pot synthesis of novel 2-oxo-1,2,3,4-tetrahydropyrimidines" in Molecular Diversity, 20, no. 3 (2016):591-604,
https://doi.org/10.1007/s11030-016-9658-y . .

TY  - JOUR
AU  - Joksimović, Nenad
AU  - Baskic, Dejan
AU  - Popovic, Suzana
AU  - Zarić, Milan
AU  - Kosanić, Marijana
AU  - Ranković, Branislav
AU  - Stanojković, Tatjana P.
AU  - Novaković, Slađana B.
AU  - Davidovic, Goran
AU  - Bugarčič, Zorica M.
AU  - Janković, Nenad
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1269
AB  - A serie of novel square pyramidal copper(II) complexes [Cu(L)(2)H2O] (3a-d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4-hydroxy-3-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth micro-dilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL(-1)) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 mu g mL(-1). The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB-DNA complex through intercalation suggesting strong competition with EB [K-sv = (1.4 +/- 0.2) and (2.9 +/- 0.1) x 10(4) M-1, respectively]. K-sv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [K-a = (2.9 +/- 0.2) x 10(6) and (2.5 +/- 0.2) x 10(5) M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d- and 3e-BSA complexes. The obtained K-a values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells.
T2  - Dalton Transactions
T1  - Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate
VL  - 45
IS  - 38
SP  - 15067
EP  - 15077
DO  - 10.1039/c6dt02257j
ER  - 

@article{
author = "Joksimović, Nenad and Baskic, Dejan and Popovic, Suzana and Zarić, Milan and Kosanić, Marijana and Ranković, Branislav and Stanojković, Tatjana P. and Novaković, Slađana B. and Davidovic, Goran and Bugarčič, Zorica M. and Janković, Nenad",
year = "2016",
abstract = "A serie of novel square pyramidal copper(II) complexes [Cu(L)(2)H2O] (3a-d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4-hydroxy-3-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth micro-dilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL(-1)) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 mu g mL(-1). The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB-DNA complex through intercalation suggesting strong competition with EB [K-sv = (1.4 +/- 0.2) and (2.9 +/- 0.1) x 10(4) M-1, respectively]. K-sv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [K-a = (2.9 +/- 0.2) x 10(6) and (2.5 +/- 0.2) x 10(5) M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d- and 3e-BSA complexes. The obtained K-a values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells.",
journal = "Dalton Transactions",
title = "Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate",
volume = "45",
number = "38",
pages = "15067-15077",
doi = "10.1039/c6dt02257j"
}

Joksimović, N., Baskic, D., Popovic, S., Zarić, M., Kosanić, M., Ranković, B., Stanojković, T. P., Novaković, S. B., Davidovic, G., Bugarčič, Z. M.,& Janković, N.. (2016). Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate. in Dalton Transactions, 45(38), 15067-15077.
https://doi.org/10.1039/c6dt02257j

Joksimović N, Baskic D, Popovic S, Zarić M, Kosanić M, Ranković B, Stanojković TP, Novaković SB, Davidovic G, Bugarčič ZM, Janković N. Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate. in Dalton Transactions. 2016;45(38):15067-15077.
doi:10.1039/c6dt02257j .

Joksimović, Nenad, Baskic, Dejan, Popovic, Suzana, Zarić, Milan, Kosanić, Marijana, Ranković, Branislav, Stanojković, Tatjana P., Novaković, Slađana B., Davidovic, Goran, Bugarčič, Zorica M., Janković, Nenad, "Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate" in Dalton Transactions, 45, no. 38 (2016):15067-15077,
https://doi.org/10.1039/c6dt02257j . .