TY  - JOUR
AU  - Janković, Nenad
AU  - Tadić, Julijana D.
AU  - Milović, Emilija
AU  - Marković, Zoran
AU  - Jeremić, Svetlana
AU  - Petronijević, Jelena
AU  - Joksimović, Nenad
AU  - Borović, Teona Teodora
AU  - Bukhari, Syed Nasir Abbas
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11100
AB  - Antioxidants have a significant contribution in the cell protection against free radicals which may induce oxidative stress, and permanently damage the cells causing different disorders such as tumors, degenerative diseases, and accelerated aging. Nowadays, a multi-functionalized heterocyclic framework plays an important role in drug development, and it is of great importance in organic synthesis and medicinal chemistry. Encouraged by the bioactivity of the pyrido-dipyrimidine scaffold and vanillin core, herein, we made an effort to thoroughly investigate the antioxidant potential of the vanillin-based pyrido-dipyrimidines A–E to reveal novel promising free radical inhibitors. The structural analysis and the antioxidant action of the investigated molecules were performed in silico by DFT calculations. Studied compounds were screened for their antioxidant capacity using in vitro ABTS and DPPH assays. All the investigated compounds showed remarkable antioxidant activity, especially derivative A exhibiting inhibition of free radicals at the IC50 value (ABTS and DPPH assay 0.1 mg ml−1 and 0.081 mg ml−1, respectively). Compound A has higher TEAC values implying its stronger antioxidant activity compared to a trolox standard. The applied calculation method and in vitro tests confirmed that compound A has a strong potential against free radicals and may be a novel candidate for application in antioxidant therapy.
T2  - RSC Advances
T1  - Investigation of the radical scavenging potential of vanillin-based pyrido-dipyrimidines: experimental and in silico approach
VL  - 13
IS  - 22
SP  - 15236
EP  - 15242
DO  - 10.1039/D3RA02469E
ER  - 

@article{
author = "Janković, Nenad and Tadić, Julijana D. and Milović, Emilija and Marković, Zoran and Jeremić, Svetlana and Petronijević, Jelena and Joksimović, Nenad and Borović, Teona Teodora and Bukhari, Syed Nasir Abbas",
year = "2023",
abstract = "Antioxidants have a significant contribution in the cell protection against free radicals which may induce oxidative stress, and permanently damage the cells causing different disorders such as tumors, degenerative diseases, and accelerated aging. Nowadays, a multi-functionalized heterocyclic framework plays an important role in drug development, and it is of great importance in organic synthesis and medicinal chemistry. Encouraged by the bioactivity of the pyrido-dipyrimidine scaffold and vanillin core, herein, we made an effort to thoroughly investigate the antioxidant potential of the vanillin-based pyrido-dipyrimidines A–E to reveal novel promising free radical inhibitors. The structural analysis and the antioxidant action of the investigated molecules were performed in silico by DFT calculations. Studied compounds were screened for their antioxidant capacity using in vitro ABTS and DPPH assays. All the investigated compounds showed remarkable antioxidant activity, especially derivative A exhibiting inhibition of free radicals at the IC50 value (ABTS and DPPH assay 0.1 mg ml−1 and 0.081 mg ml−1, respectively). Compound A has higher TEAC values implying its stronger antioxidant activity compared to a trolox standard. The applied calculation method and in vitro tests confirmed that compound A has a strong potential against free radicals and may be a novel candidate for application in antioxidant therapy.",
journal = "RSC Advances",
title = "Investigation of the radical scavenging potential of vanillin-based pyrido-dipyrimidines: experimental and in silico approach",
volume = "13",
number = "22",
pages = "15236-15242",
doi = "10.1039/D3RA02469E"
}

Janković, N., Tadić, J. D., Milović, E., Marković, Z., Jeremić, S., Petronijević, J., Joksimović, N., Borović, T. T.,& Bukhari, S. N. A.. (2023). Investigation of the radical scavenging potential of vanillin-based pyrido-dipyrimidines: experimental and in silico approach. in RSC Advances, 13(22), 15236-15242.
https://doi.org/10.1039/D3RA02469E

Janković N, Tadić JD, Milović E, Marković Z, Jeremić S, Petronijević J, Joksimović N, Borović TT, Bukhari SNA. Investigation of the radical scavenging potential of vanillin-based pyrido-dipyrimidines: experimental and in silico approach. in RSC Advances. 2023;13(22):15236-15242.
doi:10.1039/D3RA02469E .

Janković, Nenad, Tadić, Julijana D., Milović, Emilija, Marković, Zoran, Jeremić, Svetlana, Petronijević, Jelena, Joksimović, Nenad, Borović, Teona Teodora, Bukhari, Syed Nasir Abbas, "Investigation of the radical scavenging potential of vanillin-based pyrido-dipyrimidines: experimental and in silico approach" in RSC Advances, 13, no. 22 (2023):15236-15242,
https://doi.org/10.1039/D3RA02469E . .

TY  - JOUR
AU  - Joksimović, Nenad
AU  - Petronijević, Jelena
AU  - Radisavljević, Snežana
AU  - Petrović, Biljana
AU  - Mihajlović, Kristina
AU  - Janković, Nenad
AU  - Milović, Emilija
AU  - Milivojević, Dušan
AU  - Ilić, Bojana
AU  - Đurić, Ana
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10518
AB  - Considering the urgency of finding a cure for vicious diseases such as tumors, we have synthesized and characterized a small series of new copper(ii) complexes with biologically important ligands such as acylpyruvate. In addition to this, we used another four copper(ii) complexes, with ligands of the same type to examine the antitumor potential. The antitumor potential of the copper(ii) complexes was examined on three tumor cell lines and one normal human cell line using the MTT assay. All seven tested complexes showed very good cytotoxic effects. Two copper complexes that showed the best antitumor potential were selected for further testing that showed the best potential for potential application in the future. The mechanism of activity of these complexes was examined in detail using tests such as cell cycle, ROS level, oxidative DNA damage, and proteins related to hypoxia analysis. In addition, we examined the binding abilities of these complexes with biomolecules (Guo, Ino, 5′-GMP, BSA, and DNA). The results showed that the tested compounds bind strongly to DNA molecules through intercalation. Also, it has been shown that the tested compounds adequately bind to the BSA molecule, which indicates an even greater potential for some future application of these compounds in clinical practice. © 2022 The Royal Society of Chemistry.
T2  - RSC Advances
T1  - Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study
VL  - 12
IS  - 47
SP  - 30501
EP  - 30513
DO  - 10.1039/d2ra05797b
ER  - 

@article{
author = "Joksimović, Nenad and Petronijević, Jelena and Radisavljević, Snežana and Petrović, Biljana and Mihajlović, Kristina and Janković, Nenad and Milović, Emilija and Milivojević, Dušan and Ilić, Bojana and Đurić, Ana",
year = "2022",
abstract = "Considering the urgency of finding a cure for vicious diseases such as tumors, we have synthesized and characterized a small series of new copper(ii) complexes with biologically important ligands such as acylpyruvate. In addition to this, we used another four copper(ii) complexes, with ligands of the same type to examine the antitumor potential. The antitumor potential of the copper(ii) complexes was examined on three tumor cell lines and one normal human cell line using the MTT assay. All seven tested complexes showed very good cytotoxic effects. Two copper complexes that showed the best antitumor potential were selected for further testing that showed the best potential for potential application in the future. The mechanism of activity of these complexes was examined in detail using tests such as cell cycle, ROS level, oxidative DNA damage, and proteins related to hypoxia analysis. In addition, we examined the binding abilities of these complexes with biomolecules (Guo, Ino, 5′-GMP, BSA, and DNA). The results showed that the tested compounds bind strongly to DNA molecules through intercalation. Also, it has been shown that the tested compounds adequately bind to the BSA molecule, which indicates an even greater potential for some future application of these compounds in clinical practice. © 2022 The Royal Society of Chemistry.",
journal = "RSC Advances",
title = "Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study",
volume = "12",
number = "47",
pages = "30501-30513",
doi = "10.1039/d2ra05797b"
}

Joksimović, N., Petronijević, J., Radisavljević, S., Petrović, B., Mihajlović, K., Janković, N., Milović, E., Milivojević, D., Ilić, B.,& Đurić, A.. (2022). Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study. in RSC Advances, 12(47), 30501-30513.
https://doi.org/10.1039/d2ra05797b

Joksimović N, Petronijević J, Radisavljević S, Petrović B, Mihajlović K, Janković N, Milović E, Milivojević D, Ilić B, Đurić A. Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study. in RSC Advances. 2022;12(47):30501-30513.
doi:10.1039/d2ra05797b .

Joksimović, Nenad, Petronijević, Jelena, Radisavljević, Snežana, Petrović, Biljana, Mihajlović, Kristina, Janković, Nenad, Milović, Emilija, Milivojević, Dušan, Ilić, Bojana, Đurić, Ana, "Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study" in RSC Advances, 12, no. 47 (2022):30501-30513,
https://doi.org/10.1039/d2ra05797b . .

TY  - JOUR
AU  - Petronijević, Jelena
AU  - Joksimović, Nenad
AU  - Milović, Emilija
AU  - Đorđić Crnogorac, Marija
AU  - Petrović, Nina
AU  - Stanojković, Tatjana P.
AU  - Milivojević, Dušan
AU  - Janković, Nenad
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9933
AB  - In order to discover new therapeutically active agents a series of novel copper(II) complexes with 3,4-dihydro-2(1H)-quinoxalinones were synthesized. All complexes were characterized by IR and EPR spectroscopic techniques and examined for their cytotoxic effect on human cancer cell lines HeLa, LS174, A549 and normal fibroblasts (MRC-5). For further examination of the cytotoxic mechanisms of novel complexes, three of them were chosen for analysing their effects on the distribution of HeLa cells in the cell cycle phases. The results of the flow cytometry analysis suggest that tested complexes lead to time-dependent accumulation of the cells in S and G2/M phases. The strongest accumulation effect showed complex 2d after 48 h of incubation. Competitive experiments with ethidium bromide (EB) indicated that tested compound 2d have affinity to displace EB from the EB-DNA complex through intercalation. Also, the binding parameters values for 2d-BSA complex showed that a reversible 2d-BSA complex is formed and ligand 2d can be stored and carried by BSA.
T2  - Chemico-Biological Interactions
T1  - Antitumor activity, DNA and BSA interactions of novel copper(II) complexes with 3,4-dihydro-2(1H)-quinoxalinones
VL  - 348
SP  - 109647
DO  - 10.1016/j.cbi.2021.109647
ER  - 

@article{
author = "Petronijević, Jelena and Joksimović, Nenad and Milović, Emilija and Đorđić Crnogorac, Marija and Petrović, Nina and Stanojković, Tatjana P. and Milivojević, Dušan and Janković, Nenad",
year = "2021",
abstract = "In order to discover new therapeutically active agents a series of novel copper(II) complexes with 3,4-dihydro-2(1H)-quinoxalinones were synthesized. All complexes were characterized by IR and EPR spectroscopic techniques and examined for their cytotoxic effect on human cancer cell lines HeLa, LS174, A549 and normal fibroblasts (MRC-5). For further examination of the cytotoxic mechanisms of novel complexes, three of them were chosen for analysing their effects on the distribution of HeLa cells in the cell cycle phases. The results of the flow cytometry analysis suggest that tested complexes lead to time-dependent accumulation of the cells in S and G2/M phases. The strongest accumulation effect showed complex 2d after 48 h of incubation. Competitive experiments with ethidium bromide (EB) indicated that tested compound 2d have affinity to displace EB from the EB-DNA complex through intercalation. Also, the binding parameters values for 2d-BSA complex showed that a reversible 2d-BSA complex is formed and ligand 2d can be stored and carried by BSA.",
journal = "Chemico-Biological Interactions",
title = "Antitumor activity, DNA and BSA interactions of novel copper(II) complexes with 3,4-dihydro-2(1H)-quinoxalinones",
volume = "348",
pages = "109647",
doi = "10.1016/j.cbi.2021.109647"
}

Petronijević, J., Joksimović, N., Milović, E., Đorđić Crnogorac, M., Petrović, N., Stanojković, T. P., Milivojević, D.,& Janković, N.. (2021). Antitumor activity, DNA and BSA interactions of novel copper(II) complexes with 3,4-dihydro-2(1H)-quinoxalinones. in Chemico-Biological Interactions, 348, 109647.
https://doi.org/10.1016/j.cbi.2021.109647

Petronijević J, Joksimović N, Milović E, Đorđić Crnogorac M, Petrović N, Stanojković TP, Milivojević D, Janković N. Antitumor activity, DNA and BSA interactions of novel copper(II) complexes with 3,4-dihydro-2(1H)-quinoxalinones. in Chemico-Biological Interactions. 2021;348:109647.
doi:10.1016/j.cbi.2021.109647 .

Petronijević, Jelena, Joksimović, Nenad, Milović, Emilija, Đorđić Crnogorac, Marija, Petrović, Nina, Stanojković, Tatjana P., Milivojević, Dušan, Janković, Nenad, "Antitumor activity, DNA and BSA interactions of novel copper(II) complexes with 3,4-dihydro-2(1H)-quinoxalinones" in Chemico-Biological Interactions, 348 (2021):109647,
https://doi.org/10.1016/j.cbi.2021.109647 . .

TY  - JOUR
AU  - Joksimović, Nenad
AU  - Petronijević, Jelena
AU  - Janković, Nenad Ž.
AU  - Kosanić, Marijana
AU  - Milivojević, Dušan
AU  - Vraneš, Milan
AU  - Tot, Aleksandar
AU  - Bugarčić, Zorica M.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9156
AB  - Background: In order to make some progress in discovering the more effective way to eliminate ROS which cause the oxidative stress in organism in humans and bearing in mind the fact that ethyl-2-hydroxy-4-aryl(alkyl)-4-oxo-2-butenoates (β-diketonates) belong to a class of biologically active compounds, series of β-diketonates were synthesized, characterized, and tested to evaluate there antioxidant activity. Further, to investigate how coordination to copper(II) ion affects the activity of β-diketonates, appropriate complexes were synthesized and characterized. Methods: All complexes were characterized by UV-Vis, IR, and EPR spectroscopy, MS spectrometry, and elemental analysis. Fluorescence spectroscopic method was used for investigations of the interactions between biomacromolecules (DNA or BSA) and compound 2E. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and compound 2E. Results: Scavenging activity on DPPH radical revealed that compounds 2A, 2B, and 2E possess largest free radical scavenging, comparable to standard while results of superoxide anion scavenging activities of tested samples showed that maximum scavenging activity (IC50=168.92 µg/mL) was found for 2E, very similar to standard ascorbic acid, followed by 2B and 2G. Results of the interactions between biomacromolecules and 2E indicated that 2E has the affinity to displace EB from the EB-DNA complex through intercalation [Ksv = (3.7 ± 0.1) × 103 M-1], while Ka value obtained via titration of BSA with 2E [Ka = (4.2 ± 0.2) × 105 M-1], support the fact that the significant amount of the drug could be transported and distributed through the cells. Conclusions: All β-diketonates exhibited better scavenging activities than their corresponding copper complexes. Among all the tested compounds, 2E gave the highest reducing power, even higher than standard ascorbic acid, while reducing power for compounds 2A and 2B was also good but lower than standard. DNA and BSA binding study for 2E showed that this compound has the potential to be used as medicament. © 2021 Bentham Science Publishers.
T2  - Medicinal Chemistry
T1  - Synthesis, Characterization, Antioxidant Activity of β-diketonates, and Effects of Coordination to Copper(II) Ion on their Activity: DNA, BSA Interactions and Molecular Docking Study
VL  - 17
IS  - 5
SP  - 519
EP  - 532
DO  - 10.2174/1573406415666191024102520
ER  - 

@article{
author = "Joksimović, Nenad and Petronijević, Jelena and Janković, Nenad Ž. and Kosanić, Marijana and Milivojević, Dušan and Vraneš, Milan and Tot, Aleksandar and Bugarčić, Zorica M.",
year = "2021",
abstract = "Background: In order to make some progress in discovering the more effective way to eliminate ROS which cause the oxidative stress in organism in humans and bearing in mind the fact that ethyl-2-hydroxy-4-aryl(alkyl)-4-oxo-2-butenoates (β-diketonates) belong to a class of biologically active compounds, series of β-diketonates were synthesized, characterized, and tested to evaluate there antioxidant activity. Further, to investigate how coordination to copper(II) ion affects the activity of β-diketonates, appropriate complexes were synthesized and characterized. Methods: All complexes were characterized by UV-Vis, IR, and EPR spectroscopy, MS spectrometry, and elemental analysis. Fluorescence spectroscopic method was used for investigations of the interactions between biomacromolecules (DNA or BSA) and compound 2E. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and compound 2E. Results: Scavenging activity on DPPH radical revealed that compounds 2A, 2B, and 2E possess largest free radical scavenging, comparable to standard while results of superoxide anion scavenging activities of tested samples showed that maximum scavenging activity (IC50=168.92 µg/mL) was found for 2E, very similar to standard ascorbic acid, followed by 2B and 2G. Results of the interactions between biomacromolecules and 2E indicated that 2E has the affinity to displace EB from the EB-DNA complex through intercalation [Ksv = (3.7 ± 0.1) × 103 M-1], while Ka value obtained via titration of BSA with 2E [Ka = (4.2 ± 0.2) × 105 M-1], support the fact that the significant amount of the drug could be transported and distributed through the cells. Conclusions: All β-diketonates exhibited better scavenging activities than their corresponding copper complexes. Among all the tested compounds, 2E gave the highest reducing power, even higher than standard ascorbic acid, while reducing power for compounds 2A and 2B was also good but lower than standard. DNA and BSA binding study for 2E showed that this compound has the potential to be used as medicament. © 2021 Bentham Science Publishers.",
journal = "Medicinal Chemistry",
title = "Synthesis, Characterization, Antioxidant Activity of β-diketonates, and Effects of Coordination to Copper(II) Ion on their Activity: DNA, BSA Interactions and Molecular Docking Study",
volume = "17",
number = "5",
pages = "519-532",
doi = "10.2174/1573406415666191024102520"
}

Joksimović, N., Petronijević, J., Janković, N. Ž., Kosanić, M., Milivojević, D., Vraneš, M., Tot, A.,& Bugarčić, Z. M.. (2021). Synthesis, Characterization, Antioxidant Activity of β-diketonates, and Effects of Coordination to Copper(II) Ion on their Activity: DNA, BSA Interactions and Molecular Docking Study. in Medicinal Chemistry, 17(5), 519-532.
https://doi.org/10.2174/1573406415666191024102520

Joksimović N, Petronijević J, Janković NŽ, Kosanić M, Milivojević D, Vraneš M, Tot A, Bugarčić ZM. Synthesis, Characterization, Antioxidant Activity of β-diketonates, and Effects of Coordination to Copper(II) Ion on their Activity: DNA, BSA Interactions and Molecular Docking Study. in Medicinal Chemistry. 2021;17(5):519-532.
doi:10.2174/1573406415666191024102520 .

Joksimović, Nenad, Petronijević, Jelena, Janković, Nenad Ž., Kosanić, Marijana, Milivojević, Dušan, Vraneš, Milan, Tot, Aleksandar, Bugarčić, Zorica M., "Synthesis, Characterization, Antioxidant Activity of β-diketonates, and Effects of Coordination to Copper(II) Ion on their Activity: DNA, BSA Interactions and Molecular Docking Study" in Medicinal Chemistry, 17, no. 5 (2021):519-532,
https://doi.org/10.2174/1573406415666191024102520 . .

TY  - JOUR
AU  - Milović, Emilija
AU  - Janković, Nenad Ž.
AU  - Bogdanović, Goran A.
AU  - Petronijević, Jelena
AU  - Joksimović, Nenad
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9754
AB  - A simple on water approach for the synthesis of novel tetrahydropyrimidine (THPM) derivatives has been developed under a green and sustainable fashion. For the first time, a deuterated Biginelli's hybrid was synthesized. Novel THPMs are suitable for further derivatization and could be an excellent toolkit for lead-oriented synthesis and/or cross-coupling reactions. (C) 2020 Elsevier Ltd. All rights reserved.
T2  - Tetrahedron
T1  - On water synthesis of the novel 2-oxo-1,2,3,4-tetrahydropyrimidines
VL  - 78
SP  - 131790
DO  - 10.1016/j.tet.2020.131790
ER  - 

@article{
author = "Milović, Emilija and Janković, Nenad Ž. and Bogdanović, Goran A. and Petronijević, Jelena and Joksimović, Nenad",
year = "2021",
abstract = "A simple on water approach for the synthesis of novel tetrahydropyrimidine (THPM) derivatives has been developed under a green and sustainable fashion. For the first time, a deuterated Biginelli's hybrid was synthesized. Novel THPMs are suitable for further derivatization and could be an excellent toolkit for lead-oriented synthesis and/or cross-coupling reactions. (C) 2020 Elsevier Ltd. All rights reserved.",
journal = "Tetrahedron",
title = "On water synthesis of the novel 2-oxo-1,2,3,4-tetrahydropyrimidines",
volume = "78",
pages = "131790",
doi = "10.1016/j.tet.2020.131790"
}

Milović, E., Janković, N. Ž., Bogdanović, G. A., Petronijević, J.,& Joksimović, N.. (2021). On water synthesis of the novel 2-oxo-1,2,3,4-tetrahydropyrimidines. in Tetrahedron, 78, 131790.
https://doi.org/10.1016/j.tet.2020.131790

Milović E, Janković NŽ, Bogdanović GA, Petronijević J, Joksimović N. On water synthesis of the novel 2-oxo-1,2,3,4-tetrahydropyrimidines. in Tetrahedron. 2021;78:131790.
doi:10.1016/j.tet.2020.131790 .

Milović, Emilija, Janković, Nenad Ž., Bogdanović, Goran A., Petronijević, Jelena, Joksimović, Nenad, "On water synthesis of the novel 2-oxo-1,2,3,4-tetrahydropyrimidines" in Tetrahedron, 78 (2021):131790,
https://doi.org/10.1016/j.tet.2020.131790 . .

TY  - JOUR
AU  - Janković, Nenad Ž.
AU  - Trifunović Ristovski, Jovana
AU  - Vraneš, Milan
AU  - Tot, Aleksandar
AU  - Petronijević, Jelena
AU  - Joksimović, Nenad
AU  - Stanojković, Tatjana P.
AU  - Đorđić Crnogorac, Marija
AU  - Petrović, Nina
AU  - Boljević, Ivana
AU  - Matić, Ivana Z.
AU  - Bogdanović, Goran A.
AU  - Mikov, Momir
AU  - Bugarčić, Zorica M.
PY  - 2019
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0045206818312598
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8071
AB  - In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c, 4d, 4f, 4k and 4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound 4f has up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.2, 13.5 and 11.2, respectively). The obtained results from cell cycle distribution and caspase activity indicate that tested compounds (4c, 4d, 4f, 4k and 4l) promoted caspase-9 activation, implicated in the intrinsic pathway of apoptosis. Lipophilicity of 4a-l was determinate by using reversed-phase high-performance liquid chromatography. © 2019 Elsevier Inc.
T2  - Bioorganic Chemistry
T1  - Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels
VL  - 86
SP  - 569
EP  - 582
DO  - 10.1016/j.bioorg.2019.02.026
ER  - 

@article{
author = "Janković, Nenad Ž. and Trifunović Ristovski, Jovana and Vraneš, Milan and Tot, Aleksandar and Petronijević, Jelena and Joksimović, Nenad and Stanojković, Tatjana P. and Đorđić Crnogorac, Marija and Petrović, Nina and Boljević, Ivana and Matić, Ivana Z. and Bogdanović, Goran A. and Mikov, Momir and Bugarčić, Zorica M.",
year = "2019",
abstract = "In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c, 4d, 4f, 4k and 4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound 4f has up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.2, 13.5 and 11.2, respectively). The obtained results from cell cycle distribution and caspase activity indicate that tested compounds (4c, 4d, 4f, 4k and 4l) promoted caspase-9 activation, implicated in the intrinsic pathway of apoptosis. Lipophilicity of 4a-l was determinate by using reversed-phase high-performance liquid chromatography. © 2019 Elsevier Inc.",
journal = "Bioorganic Chemistry",
title = "Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels",
volume = "86",
pages = "569-582",
doi = "10.1016/j.bioorg.2019.02.026"
}

Janković, N. Ž., Trifunović Ristovski, J., Vraneš, M., Tot, A., Petronijević, J., Joksimović, N., Stanojković, T. P., Đorđić Crnogorac, M., Petrović, N., Boljević, I., Matić, I. Z., Bogdanović, G. A., Mikov, M.,& Bugarčić, Z. M.. (2019). Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels. in Bioorganic Chemistry, 86, 569-582.
https://doi.org/10.1016/j.bioorg.2019.02.026

Janković NŽ, Trifunović Ristovski J, Vraneš M, Tot A, Petronijević J, Joksimović N, Stanojković TP, Đorđić Crnogorac M, Petrović N, Boljević I, Matić IZ, Bogdanović GA, Mikov M, Bugarčić ZM. Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels. in Bioorganic Chemistry. 2019;86:569-582.
doi:10.1016/j.bioorg.2019.02.026 .

Janković, Nenad Ž., Trifunović Ristovski, Jovana, Vraneš, Milan, Tot, Aleksandar, Petronijević, Jelena, Joksimović, Nenad, Stanojković, Tatjana P., Đorđić Crnogorac, Marija, Petrović, Nina, Boljević, Ivana, Matić, Ivana Z., Bogdanović, Goran A., Mikov, Momir, Bugarčić, Zorica M., "Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels" in Bioorganic Chemistry, 86 (2019):569-582,
https://doi.org/10.1016/j.bioorg.2019.02.026 . .

TY  - JOUR
AU  - Joksimović, Nenad
AU  - Petronijević, Jelena
AU  - Janković, Nenad Ž.
AU  - Baskić, Dejan
AU  - Popović, Suzana Lj.
AU  - Todorović, Danijela V.
AU  - Matić, Sanja Lj.
AU  - Bogdanović, Goran A.
AU  - Vraneš, Milan
AU  - Tot, Aleksandar
AU  - Bugarčić, Zorica M.
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8173
AB  - In order to make a progress in discovering a new agents for chemotherapy with improved properties and bearing in mind the fact that substituted 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, series of novel 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones were synthesized and characterized by spectral (UV–Vis, IR, NMR, ESI-MS), X-ray and elemental analysis. All compounds were examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Four compounds, 3-hydroxy-1-(p-tolyl)-4-(2-thienylcarbonyl)-5-(4-chlorophenyl)-2,5-dihydro-1H-pyrrol-2-one (D10), 3-hydroxy-1-(3-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D13), 3-hydroxy-1-(4-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D14), and 3-hydroxy-1-(4-chlorophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D15), that showed the highest cytotoxicity against malignant cells and the best selectivity towards normal cells were selected for further experiments. Results obtained by investigating mechanisms of cytotoxic activity suggest that selected 3-hydroxy-3-pyrrolin-2-one derivatives in HeLa cells induce apoptosis that is associated with S phase arrest (D13, D15, and D10) or unrelated to cell cycle distribution (D14). Additionally, to better understand their suitability for potential use as anticancer medicaments we studied the interactions between biomacromolecules (DNA or BSA) and D13 and D15. The results indicated that D13 and D15 have great affinity to displace EB from the EB-DNA complex through intercalation [K sv = (3.7 ± 0.1) and (3.4 ± 0.1) × 10 3 M −1 , respectively], an intercalative mode also confirmed through viscosity measurements. K a values, obtained as result of fluorescence titration of BSA with D13 and D15 [K a = (4.2 ± 0.2) and (2.6 ± 0.2) × 10 5 M, respectively], support the fact that a significant amount of the tested compounds could be transported and distributed through the cells. In addition, by DNA and BSA molecular docking study for D13, D14 and D15 is determined and predicted the binding mode and the interaction region. © 2019 Elsevier Inc.
T2  - Bioorganic Chemistry
T1  - Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study
VL  - 88
SP  - 102954
DO  - 10.1016/j.bioorg.2019.102954
ER  - 

@article{
author = "Joksimović, Nenad and Petronijević, Jelena and Janković, Nenad Ž. and Baskić, Dejan and Popović, Suzana Lj. and Todorović, Danijela V. and Matić, Sanja Lj. and Bogdanović, Goran A. and Vraneš, Milan and Tot, Aleksandar and Bugarčić, Zorica M.",
year = "2019",
abstract = "In order to make a progress in discovering a new agents for chemotherapy with improved properties and bearing in mind the fact that substituted 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, series of novel 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones were synthesized and characterized by spectral (UV–Vis, IR, NMR, ESI-MS), X-ray and elemental analysis. All compounds were examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Four compounds, 3-hydroxy-1-(p-tolyl)-4-(2-thienylcarbonyl)-5-(4-chlorophenyl)-2,5-dihydro-1H-pyrrol-2-one (D10), 3-hydroxy-1-(3-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D13), 3-hydroxy-1-(4-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D14), and 3-hydroxy-1-(4-chlorophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D15), that showed the highest cytotoxicity against malignant cells and the best selectivity towards normal cells were selected for further experiments. Results obtained by investigating mechanisms of cytotoxic activity suggest that selected 3-hydroxy-3-pyrrolin-2-one derivatives in HeLa cells induce apoptosis that is associated with S phase arrest (D13, D15, and D10) or unrelated to cell cycle distribution (D14). Additionally, to better understand their suitability for potential use as anticancer medicaments we studied the interactions between biomacromolecules (DNA or BSA) and D13 and D15. The results indicated that D13 and D15 have great affinity to displace EB from the EB-DNA complex through intercalation [K sv = (3.7 ± 0.1) and (3.4 ± 0.1) × 10 3 M −1 , respectively], an intercalative mode also confirmed through viscosity measurements. K a values, obtained as result of fluorescence titration of BSA with D13 and D15 [K a = (4.2 ± 0.2) and (2.6 ± 0.2) × 10 5 M, respectively], support the fact that a significant amount of the tested compounds could be transported and distributed through the cells. In addition, by DNA and BSA molecular docking study for D13, D14 and D15 is determined and predicted the binding mode and the interaction region. © 2019 Elsevier Inc.",
journal = "Bioorganic Chemistry",
title = "Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study",
volume = "88",
pages = "102954",
doi = "10.1016/j.bioorg.2019.102954"
}

Joksimović, N., Petronijević, J., Janković, N. Ž., Baskić, D., Popović, S. Lj., Todorović, D. V., Matić, S. Lj., Bogdanović, G. A., Vraneš, M., Tot, A.,& Bugarčić, Z. M.. (2019). Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study. in Bioorganic Chemistry, 88, 102954.
https://doi.org/10.1016/j.bioorg.2019.102954

Joksimović N, Petronijević J, Janković NŽ, Baskić D, Popović SL, Todorović DV, Matić SL, Bogdanović GA, Vraneš M, Tot A, Bugarčić ZM. Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study. in Bioorganic Chemistry. 2019;88:102954.
doi:10.1016/j.bioorg.2019.102954 .

Joksimović, Nenad, Petronijević, Jelena, Janković, Nenad Ž., Baskić, Dejan, Popović, Suzana Lj., Todorović, Danijela V., Matić, Sanja Lj., Bogdanović, Goran A., Vraneš, Milan, Tot, Aleksandar, Bugarčić, Zorica M., "Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study" in Bioorganic Chemistry, 88 (2019):102954,
https://doi.org/10.1016/j.bioorg.2019.102954 . .

TY  - JOUR
AU  - Joksimović, Nenad
AU  - Petronijević, Jelena
AU  - Janković, Nenad Ž.
AU  - Baskić, Dejan
AU  - Popović, Suzana Lj.
AU  - Todorović, Danijela V.
AU  - Matić, Sanja Lj.
AU  - Bogdanović, Goran A.
AU  - Vraneš, Milan
AU  - Tot, Aleksandar
AU  - Bugarčić, Zorica M.
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8186
AB  - In order to make a progress in discovering a new agents for chemotherapy with improved properties and bearing in mind the fact that substituted 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, series of novel 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones were synthesized and characterized by spectral (UV–Vis, IR, NMR, ESI-MS), X-ray and elemental analysis. All compounds were examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Four compounds, 3-hydroxy-1-(p-tolyl)-4-(2-thienylcarbonyl)-5-(4-chlorophenyl)-2,5-dihydro-1H-pyrrol-2-one (D10), 3-hydroxy-1-(3-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D13), 3-hydroxy-1-(4-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D14), and 3-hydroxy-1-(4-chlorophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D15), that showed the highest cytotoxicity against malignant cells and the best selectivity towards normal cells were selected for further experiments. Results obtained by investigating mechanisms of cytotoxic activity suggest that selected 3-hydroxy-3-pyrrolin-2-one derivatives in HeLa cells induce apoptosis that is associated with S phase arrest (D13, D15, and D10) or unrelated to cell cycle distribution (D14). Additionally, to better understand their suitability for potential use as anticancer medicaments we studied the interactions between biomacromolecules (DNA or BSA) and D13 and D15. The results indicated that D13 and D15 have great affinity to displace EB from the EB-DNA complex through intercalation [K sv = (3.7 ± 0.1) and (3.4 ± 0.1) × 10 3 M −1 , respectively], an intercalative mode also confirmed through viscosity measurements. K a values, obtained as result of fluorescence titration of BSA with D13 and D15 [K a = (4.2 ± 0.2) and (2.6 ± 0.2) × 10 5 M, respectively], support the fact that a significant amount of the tested compounds could be transported and distributed through the cells. In addition, by DNA and BSA molecular docking study for D13, D14 and D15 is determined and predicted the binding mode and the interaction region. © 2019 Elsevier Inc.
T2  - Bioorganic Chemistry
T1  - Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study
VL  - 88
SP  - 102954
DO  - 10.1016/j.bioorg.2019.102954
ER  - 

@article{
author = "Joksimović, Nenad and Petronijević, Jelena and Janković, Nenad Ž. and Baskić, Dejan and Popović, Suzana Lj. and Todorović, Danijela V. and Matić, Sanja Lj. and Bogdanović, Goran A. and Vraneš, Milan and Tot, Aleksandar and Bugarčić, Zorica M.",
year = "2019",
abstract = "In order to make a progress in discovering a new agents for chemotherapy with improved properties and bearing in mind the fact that substituted 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, series of novel 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones were synthesized and characterized by spectral (UV–Vis, IR, NMR, ESI-MS), X-ray and elemental analysis. All compounds were examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Four compounds, 3-hydroxy-1-(p-tolyl)-4-(2-thienylcarbonyl)-5-(4-chlorophenyl)-2,5-dihydro-1H-pyrrol-2-one (D10), 3-hydroxy-1-(3-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D13), 3-hydroxy-1-(4-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D14), and 3-hydroxy-1-(4-chlorophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D15), that showed the highest cytotoxicity against malignant cells and the best selectivity towards normal cells were selected for further experiments. Results obtained by investigating mechanisms of cytotoxic activity suggest that selected 3-hydroxy-3-pyrrolin-2-one derivatives in HeLa cells induce apoptosis that is associated with S phase arrest (D13, D15, and D10) or unrelated to cell cycle distribution (D14). Additionally, to better understand their suitability for potential use as anticancer medicaments we studied the interactions between biomacromolecules (DNA or BSA) and D13 and D15. The results indicated that D13 and D15 have great affinity to displace EB from the EB-DNA complex through intercalation [K sv = (3.7 ± 0.1) and (3.4 ± 0.1) × 10 3 M −1 , respectively], an intercalative mode also confirmed through viscosity measurements. K a values, obtained as result of fluorescence titration of BSA with D13 and D15 [K a = (4.2 ± 0.2) and (2.6 ± 0.2) × 10 5 M, respectively], support the fact that a significant amount of the tested compounds could be transported and distributed through the cells. In addition, by DNA and BSA molecular docking study for D13, D14 and D15 is determined and predicted the binding mode and the interaction region. © 2019 Elsevier Inc.",
journal = "Bioorganic Chemistry",
title = "Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study",
volume = "88",
pages = "102954",
doi = "10.1016/j.bioorg.2019.102954"
}

Joksimović, N., Petronijević, J., Janković, N. Ž., Baskić, D., Popović, S. Lj., Todorović, D. V., Matić, S. Lj., Bogdanović, G. A., Vraneš, M., Tot, A.,& Bugarčić, Z. M.. (2019). Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study. in Bioorganic Chemistry, 88, 102954.
https://doi.org/10.1016/j.bioorg.2019.102954

Joksimović N, Petronijević J, Janković NŽ, Baskić D, Popović SL, Todorović DV, Matić SL, Bogdanović GA, Vraneš M, Tot A, Bugarčić ZM. Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study. in Bioorganic Chemistry. 2019;88:102954.
doi:10.1016/j.bioorg.2019.102954 .

Joksimović, Nenad, Petronijević, Jelena, Janković, Nenad Ž., Baskić, Dejan, Popović, Suzana Lj., Todorović, Danijela V., Matić, Sanja Lj., Bogdanović, Goran A., Vraneš, Milan, Tot, Aleksandar, Bugarčić, Zorica M., "Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study" in Bioorganic Chemistry, 88 (2019):102954,
https://doi.org/10.1016/j.bioorg.2019.102954 . .

TY  - DATA
AU  - Janković, Nenad Ž.
AU  - Stefanović, Srđan M.
AU  - Petronijević, Jelena
AU  - Joksimović, Nenad
AU  - Novaković, Slađana B.
AU  - Bogdanović, Goran A.
AU  - Muškinja, Jovana
AU  - Vraneš, Milan
AU  - Ratković, Zoran R.
AU  - Bugarčić, Zorica M.
PY  - 2018
UR  - http://pubs.acs.org/doi/10.1021/acssuschemeng.8b03127
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7886
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7888
AB  - The selective synthesis of 5,6-dihydropyrimidin-4(3H)-one scaffold (precursor of dihydrouracil) was a very difficult synthetic challenge that, so far, has not been achieved. For the first time, in this paper, green, selective and high-yields approach to 40 novel 5,6-dihydropyrimidin-4(3H)-ones (DHPMs) by one-pot reaction of aldehydes, Meldrum's acid and isothioureas under solvent-free conditions, in the presence of water, since an additive is presented. In the majority of cases, introduced methodology gave an unprecedented tautomer-selective fashion toward targeted compounds with excellent tautomeric purity (>99.9%), which reached 100% in few cases. The molecular structure of the five compounds has been determined by X-ray crystallography. In each one of them, very short length for the corresponding N2-C1 bond was noticed, making them especially interesting from a structural standpoint. This experimental fact can imply a highly localized electron π density in this part of each heterocyclic ring. The obtained experimental results, which are determined from NMR and ESI-MS study, indicate that this Biginelli-type reaction smoothly proceeds in a one-pot mode, pointing to the three-step tandem process, proceeding via the Knoevenagel, aza-Michael, and retro-Diels-Alder reactions. The presented strategy also had the following advantages: reduction amount of waste, excellent values of green chemistry metrics (cEF, EcoScale and GCIS), and it is the first eco-friendly strategy toward the DHPMs scaffold. © Copyright 2018 American Chemical Society.
T2  - ACS Sustainable Chemistry and Engineering
T1  - Supporting information for: Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3 H )-ones, Driven under the Umbrella of Sustainable Chemistry
VL  - 6
IS  - 10
SP  - 13358
EP  - 13366
DO  - 10.1021/acssuschemeng.8b03127.s006
ER  - 

@misc{
author = "Janković, Nenad Ž. and Stefanović, Srđan M. and Petronijević, Jelena and Joksimović, Nenad and Novaković, Slađana B. and Bogdanović, Goran A. and Muškinja, Jovana and Vraneš, Milan and Ratković, Zoran R. and Bugarčić, Zorica M.",
year = "2018",
abstract = "The selective synthesis of 5,6-dihydropyrimidin-4(3H)-one scaffold (precursor of dihydrouracil) was a very difficult synthetic challenge that, so far, has not been achieved. For the first time, in this paper, green, selective and high-yields approach to 40 novel 5,6-dihydropyrimidin-4(3H)-ones (DHPMs) by one-pot reaction of aldehydes, Meldrum's acid and isothioureas under solvent-free conditions, in the presence of water, since an additive is presented. In the majority of cases, introduced methodology gave an unprecedented tautomer-selective fashion toward targeted compounds with excellent tautomeric purity (>99.9%), which reached 100% in few cases. The molecular structure of the five compounds has been determined by X-ray crystallography. In each one of them, very short length for the corresponding N2-C1 bond was noticed, making them especially interesting from a structural standpoint. This experimental fact can imply a highly localized electron π density in this part of each heterocyclic ring. The obtained experimental results, which are determined from NMR and ESI-MS study, indicate that this Biginelli-type reaction smoothly proceeds in a one-pot mode, pointing to the three-step tandem process, proceeding via the Knoevenagel, aza-Michael, and retro-Diels-Alder reactions. The presented strategy also had the following advantages: reduction amount of waste, excellent values of green chemistry metrics (cEF, EcoScale and GCIS), and it is the first eco-friendly strategy toward the DHPMs scaffold. © Copyright 2018 American Chemical Society.",
journal = "ACS Sustainable Chemistry and Engineering",
title = "Supporting information for: Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3 H )-ones, Driven under the Umbrella of Sustainable Chemistry",
volume = "6",
number = "10",
pages = "13358-13366",
doi = "10.1021/acssuschemeng.8b03127.s006"
}

Janković, N. Ž., Stefanović, S. M., Petronijević, J., Joksimović, N., Novaković, S. B., Bogdanović, G. A., Muškinja, J., Vraneš, M., Ratković, Z. R.,& Bugarčić, Z. M.. (2018). Supporting information for: Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3 H )-ones, Driven under the Umbrella of Sustainable Chemistry. in ACS Sustainable Chemistry and Engineering, 6(10), 13358-13366.
https://doi.org/10.1021/acssuschemeng.8b03127.s006

Janković NŽ, Stefanović SM, Petronijević J, Joksimović N, Novaković SB, Bogdanović GA, Muškinja J, Vraneš M, Ratković ZR, Bugarčić ZM. Supporting information for: Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3 H )-ones, Driven under the Umbrella of Sustainable Chemistry. in ACS Sustainable Chemistry and Engineering. 2018;6(10):13358-13366.
doi:10.1021/acssuschemeng.8b03127.s006 .

Janković, Nenad Ž., Stefanović, Srđan M., Petronijević, Jelena, Joksimović, Nenad, Novaković, Slađana B., Bogdanović, Goran A., Muškinja, Jovana, Vraneš, Milan, Ratković, Zoran R., Bugarčić, Zorica M., "Supporting information for: Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3 H )-ones, Driven under the Umbrella of Sustainable Chemistry" in ACS Sustainable Chemistry and Engineering, 6, no. 10 (2018):13358-13366,
https://doi.org/10.1021/acssuschemeng.8b03127.s006 . .

TY  - JOUR
AU  - Janković, Nenad Ž.
AU  - Stefanović, Srđan M.
AU  - Petronijević, Jelena
AU  - Joksimović, Nenad
AU  - Novaković, Slađana B.
AU  - Bogdanović, Goran A.
AU  - Muškinja, Jovana
AU  - Vraneš, Milan
AU  - Ratković, Zoran R.
AU  - Bugarčić, Zorica M.
PY  - 2018
UR  - http://pubs.acs.org/doi/10.1021/acssuschemeng.8b03127
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7886
AB  - The selective synthesis of 5,6-dihydropyrimidin-4(3H)-one scaffold (precursor of dihydrouracil) was a very difficult synthetic challenge that, so far, has not been achieved. For the first time, in this paper, green, selective and high-yields approach to 40 novel 5,6-dihydropyrimidin-4(3H)-ones (DHPMs) by one-pot reaction of aldehydes, Meldrum's acid and isothioureas under solvent-free conditions, in the presence of water, since an additive is presented. In the majority of cases, introduced methodology gave an unprecedented tautomer-selective fashion toward targeted compounds with excellent tautomeric purity (>99.9%), which reached 100% in few cases. The molecular structure of the five compounds has been determined by X-ray crystallography. In each one of them, very short length for the corresponding N2-C1 bond was noticed, making them especially interesting from a structural standpoint. This experimental fact can imply a highly localized electron π density in this part of each heterocyclic ring. The obtained experimental results, which are determined from NMR and ESI-MS study, indicate that this Biginelli-type reaction smoothly proceeds in a one-pot mode, pointing to the three-step tandem process, proceeding via the Knoevenagel, aza-Michael, and retro-Diels-Alder reactions. The presented strategy also had the following advantages: reduction amount of waste, excellent values of green chemistry metrics (cEF, EcoScale and GCIS), and it is the first eco-friendly strategy toward the DHPMs scaffold. © Copyright 2018 American Chemical Society.
T2  - ACS Sustainable Chemistry and Engineering
T1  - Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3 H )-ones, Driven under the Umbrella of Sustainable Chemistry
VL  - 6
IS  - 10
SP  - 13358
EP  - 13366
DO  - 10.1021/acssuschemeng.8b03127
ER  - 

@article{
author = "Janković, Nenad Ž. and Stefanović, Srđan M. and Petronijević, Jelena and Joksimović, Nenad and Novaković, Slađana B. and Bogdanović, Goran A. and Muškinja, Jovana and Vraneš, Milan and Ratković, Zoran R. and Bugarčić, Zorica M.",
year = "2018",
abstract = "The selective synthesis of 5,6-dihydropyrimidin-4(3H)-one scaffold (precursor of dihydrouracil) was a very difficult synthetic challenge that, so far, has not been achieved. For the first time, in this paper, green, selective and high-yields approach to 40 novel 5,6-dihydropyrimidin-4(3H)-ones (DHPMs) by one-pot reaction of aldehydes, Meldrum's acid and isothioureas under solvent-free conditions, in the presence of water, since an additive is presented. In the majority of cases, introduced methodology gave an unprecedented tautomer-selective fashion toward targeted compounds with excellent tautomeric purity (>99.9%), which reached 100% in few cases. The molecular structure of the five compounds has been determined by X-ray crystallography. In each one of them, very short length for the corresponding N2-C1 bond was noticed, making them especially interesting from a structural standpoint. This experimental fact can imply a highly localized electron π density in this part of each heterocyclic ring. The obtained experimental results, which are determined from NMR and ESI-MS study, indicate that this Biginelli-type reaction smoothly proceeds in a one-pot mode, pointing to the three-step tandem process, proceeding via the Knoevenagel, aza-Michael, and retro-Diels-Alder reactions. The presented strategy also had the following advantages: reduction amount of waste, excellent values of green chemistry metrics (cEF, EcoScale and GCIS), and it is the first eco-friendly strategy toward the DHPMs scaffold. © Copyright 2018 American Chemical Society.",
journal = "ACS Sustainable Chemistry and Engineering",
title = "Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3 H )-ones, Driven under the Umbrella of Sustainable Chemistry",
volume = "6",
number = "10",
pages = "13358-13366",
doi = "10.1021/acssuschemeng.8b03127"
}

Janković, N. Ž., Stefanović, S. M., Petronijević, J., Joksimović, N., Novaković, S. B., Bogdanović, G. A., Muškinja, J., Vraneš, M., Ratković, Z. R.,& Bugarčić, Z. M.. (2018). Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3 H )-ones, Driven under the Umbrella of Sustainable Chemistry. in ACS Sustainable Chemistry and Engineering, 6(10), 13358-13366.
https://doi.org/10.1021/acssuschemeng.8b03127

Janković NŽ, Stefanović SM, Petronijević J, Joksimović N, Novaković SB, Bogdanović GA, Muškinja J, Vraneš M, Ratković ZR, Bugarčić ZM. Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3 H )-ones, Driven under the Umbrella of Sustainable Chemistry. in ACS Sustainable Chemistry and Engineering. 2018;6(10):13358-13366.
doi:10.1021/acssuschemeng.8b03127 .

Janković, Nenad Ž., Stefanović, Srđan M., Petronijević, Jelena, Joksimović, Nenad, Novaković, Slađana B., Bogdanović, Goran A., Muškinja, Jovana, Vraneš, Milan, Ratković, Zoran R., Bugarčić, Zorica M., "Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3 H )-ones, Driven under the Umbrella of Sustainable Chemistry" in ACS Sustainable Chemistry and Engineering, 6, no. 10 (2018):13358-13366,
https://doi.org/10.1021/acssuschemeng.8b03127 . .

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 . .