TY  - JOUR
AU  - Nedeljković, Nikola
AU  - Nikolić, Miloš
AU  - Čanović, Petar
AU  - Zarić, Milan
AU  - Živković-Zarić, Radica
AU  - Bošković, Jelena
AU  - Vesović, Marina
AU  - Bradić, Jovana
AU  - Anđić, Marijana
AU  - Kočović, Aleksandar
AU  - Nikolić, Marina
AU  - Jakovljević, Vladimir
AU  - Vujić, Zorica
AU  - Dobričić, Vladimir
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5449
AB  - The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8–14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1–7 and 8–14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 μM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents.
PB  - MDPI
T2  - Pharmaceutics
T1  - Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen
VL  - 16
IS  - 1
SP  - 1
DO  - 10.3390/pharmaceutics16010001
ER  - 

@article{
author = "Nedeljković, Nikola and Nikolić, Miloš and Čanović, Petar and Zarić, Milan and Živković-Zarić, Radica and Bošković, Jelena and Vesović, Marina and Bradić, Jovana and Anđić, Marijana and Kočović, Aleksandar and Nikolić, Marina and Jakovljević, Vladimir and Vujić, Zorica and Dobričić, Vladimir",
year = "2024",
abstract = "The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8–14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1–7 and 8–14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 μM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen",
volume = "16",
number = "1",
pages = "1",
doi = "10.3390/pharmaceutics16010001"
}

Nedeljković, N., Nikolić, M., Čanović, P., Zarić, M., Živković-Zarić, R., Bošković, J., Vesović, M., Bradić, J., Anđić, M., Kočović, A., Nikolić, M., Jakovljević, V., Vujić, Z.,& Dobričić, V.. (2024). Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen. in Pharmaceutics
MDPI., 16(1), 1.
https://doi.org/10.3390/pharmaceutics16010001

Nedeljković N, Nikolić M, Čanović P, Zarić M, Živković-Zarić R, Bošković J, Vesović M, Bradić J, Anđić M, Kočović A, Nikolić M, Jakovljević V, Vujić Z, Dobričić V. Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen. in Pharmaceutics. 2024;16(1):1.
doi:10.3390/pharmaceutics16010001 .

Nedeljković, Nikola, Nikolić, Miloš, Čanović, Petar, Zarić, Milan, Živković-Zarić, Radica, Bošković, Jelena, Vesović, Marina, Bradić, Jovana, Anđić, Marijana, Kočović, Aleksandar, Nikolić, Marina, Jakovljević, Vladimir, Vujić, Zorica, Dobričić, Vladimir, "Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen" in Pharmaceutics, 16, no. 1 (2024):1,
https://doi.org/10.3390/pharmaceutics16010001 . .

TY  - CONF
AU  - Bošković, Jelena
AU  - Dobričić, Vladimir
AU  - Nedeljković, Nikola
AU  - Nikolić, Miloš
AU  - Vujić, Zorica
AU  - Čudina, Olivera
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5458
AB  - The pathogenesis and progression of a various diseases, such as cancer, rheumatoid arthritis, autoimmune, cardiovascular and neurodegenerative diseases, are closely related to chronic inflammatory processes. ...
PB  - European Federation for Medicinal chemistry and Chemical biology (EFMC)
C3  - EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts
T1  - Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors
SP  - 154
EP  - 154
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5458
ER  - 

@conference{
author = "Bošković, Jelena and Dobričić, Vladimir and Nedeljković, Nikola and Nikolić, Miloš and Vujić, Zorica and Čudina, Olivera",
year = "2023",
abstract = "The pathogenesis and progression of a various diseases, such as cancer, rheumatoid arthritis, autoimmune, cardiovascular and neurodegenerative diseases, are closely related to chronic inflammatory processes. ...",
publisher = "European Federation for Medicinal chemistry and Chemical biology (EFMC)",
journal = "EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts",
title = "Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors",
pages = "154-154",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5458"
}

Bošković, J., Dobričić, V., Nedeljković, N., Nikolić, M., Vujić, Z.,& Čudina, O.. (2023). Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors. in EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts
European Federation for Medicinal chemistry and Chemical biology (EFMC)., 154-154.
https://hdl.handle.net/21.15107/rcub_farfar_5458

Bošković J, Dobričić V, Nedeljković N, Nikolić M, Vujić Z, Čudina O. Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors. in EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts. 2023;:154-154.
https://hdl.handle.net/21.15107/rcub_farfar_5458 .

Bošković, Jelena, Dobričić, Vladimir, Nedeljković, Nikola, Nikolić, Miloš, Vujić, Zorica, Čudina, Olivera, "Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors" in EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts (2023):154-154,
https://hdl.handle.net/21.15107/rcub_farfar_5458 .

TY  - JOUR
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Mijajlović, Marina
AU  - Vujić, Zorica
AU  - Nikolić, Miloš
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5347
AB  - Naproxen, as a propionic acid derivative, causes serious gastrointestinal side effects due to the presence of free carboxylic group. In that sense, masking of carboxylic group with other pharmacophores may be a promising strategy to decrease gastrointestinal toxicity. Thiourea derivatives have been intensively investigated as potential antitumor drugs, whereby their activity is based on potential inhibition of protein kinases, topoisomerases, carbonic anhydrase and sirtuins. In addition, it was shown that inhibition of certain protein kinases might reverse resistance to chemotherapeutic drugs by enhancing the cell death in the presence of low concentrations of drug. Twenty new thiourea derivatives of naproxen were designed and their binding to four selected protein kinases involved in tumor multidrug resistance (AKT2, mTOR, EGFR and VEGFR1) was estimated using two molecular docking programs (AutoDock Vina and OEDocking). According to OEDocking, the highest potential to inhibit AKT2 and mTor has derivative 1, while derivative 20 demonstrates the highest potential towards EGFR and VEGFR1. According to AutoDock Vina, the highest potential for inhibition of EGFR, AKT2 and VEGFR1 have derivatives 16 and 17. Therefore, derivatives 1, 16, 17 and 20 are potentially the most potent protein kinase inhibitors that could be further synthesized and tested for anticancer activity.
PB  - Sciendo
T2  - Experimental and Applied Biomedical Research (EABR)
T1  - Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity
VL  - 24
IS  - 3
SP  - 235
EP  - 242
DO  - 10.2478/sjecr-2021-0037
ER  - 

@article{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Mijajlović, Marina and Vujić, Zorica and Nikolić, Miloš",
year = "2023",
abstract = "Naproxen, as a propionic acid derivative, causes serious gastrointestinal side effects due to the presence of free carboxylic group. In that sense, masking of carboxylic group with other pharmacophores may be a promising strategy to decrease gastrointestinal toxicity. Thiourea derivatives have been intensively investigated as potential antitumor drugs, whereby their activity is based on potential inhibition of protein kinases, topoisomerases, carbonic anhydrase and sirtuins. In addition, it was shown that inhibition of certain protein kinases might reverse resistance to chemotherapeutic drugs by enhancing the cell death in the presence of low concentrations of drug. Twenty new thiourea derivatives of naproxen were designed and their binding to four selected protein kinases involved in tumor multidrug resistance (AKT2, mTOR, EGFR and VEGFR1) was estimated using two molecular docking programs (AutoDock Vina and OEDocking). According to OEDocking, the highest potential to inhibit AKT2 and mTor has derivative 1, while derivative 20 demonstrates the highest potential towards EGFR and VEGFR1. According to AutoDock Vina, the highest potential for inhibition of EGFR, AKT2 and VEGFR1 have derivatives 16 and 17. Therefore, derivatives 1, 16, 17 and 20 are potentially the most potent protein kinase inhibitors that could be further synthesized and tested for anticancer activity.",
publisher = "Sciendo",
journal = "Experimental and Applied Biomedical Research (EABR)",
title = "Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity",
volume = "24",
number = "3",
pages = "235-242",
doi = "10.2478/sjecr-2021-0037"
}

Nedeljković, N., Dobričić, V., Mijajlović, M., Vujić, Z.,& Nikolić, M.. (2023). Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity. in Experimental and Applied Biomedical Research (EABR)
Sciendo., 24(3), 235-242.
https://doi.org/10.2478/sjecr-2021-0037

Nedeljković N, Dobričić V, Mijajlović M, Vujić Z, Nikolić M. Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity. in Experimental and Applied Biomedical Research (EABR). 2023;24(3):235-242.
doi:10.2478/sjecr-2021-0037 .

Nedeljković, Nikola, Dobričić, Vladimir, Mijajlović, Marina, Vujić, Zorica, Nikolić, Miloš, "Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Antitumor Activity" in Experimental and Applied Biomedical Research (EABR), 24, no. 3 (2023):235-242,
https://doi.org/10.2478/sjecr-2021-0037 . .

TY  - CONF
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Mijajlović, Marina
AU  - Vujić, Zorica
AU  - Nikolić, Miloš
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4996
AB  - Administration of current non-steroidal anti-inflammatory drugs is often associated with
serious adverse effects. Therefore, there is a constant need to develop new molecules with anti-
inflammatory activity. On the other hand, thiourea derivatives of non-steroidal anti-inflammatory
drugs demonstrated significant anti-inflammatory activity in numerous studies. To clarify anti-
inflammatory mechanism of action, in silico study was performed on four thiourea derivatives of
naproxen, which were selected from the initial group of compounds synthesized by our research
group. Tested compounds contain p-fluoroaniline (16), p-methoxyaniline (17), p-ethoxyaniline (18)
and aniline (19) in the side chains. Selected 3D structures of enzymes COX-2 (3NT1) and 5-LOX
(6NCF) were taken from PDB database. MAKE Receptor 3.2.0.2 software (OpenEye Scientific Software,
Inc, Santa Fe, NM, United States) was used for preparation of enzymes’ active sites, while ligands
were prepared in OMEGA 2.5.1.4. FRED 3.2.0.2 software (OpenEye Scientific Software, Inc, Santa
Fe, NM, United States) was employed for the analysis of binding poses into enzymes’ active sites.
All tested compounds showed key binding interactions with both enzymes. The highest number
of key binding interactions was observed during molecular fitting of derivative 19 into the active
site of COX-2 and derivatives 16 and 18 into the 5-LOX. Derivative 17 had the lowest value of free
binding energy for both target enzymes (−14.90 kcal/mol for COX-2 and −9.57 kcal/mol for 5-LOX).
Therefore, all analyzed compounds represent potential dual inhibitors of mentioned enzymes.
PB  - MDPI
C3  - Medical Sciences Forum
T1  - Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity
VL  - 14
IS  - 1
DO  - 10.3390/ECMC2022-13279
ER  - 

@conference{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Mijajlović, Marina and Vujić, Zorica and Nikolić, Miloš",
year = "2022",
abstract = "Administration of current non-steroidal anti-inflammatory drugs is often associated with
serious adverse effects. Therefore, there is a constant need to develop new molecules with anti-
inflammatory activity. On the other hand, thiourea derivatives of non-steroidal anti-inflammatory
drugs demonstrated significant anti-inflammatory activity in numerous studies. To clarify anti-
inflammatory mechanism of action, in silico study was performed on four thiourea derivatives of
naproxen, which were selected from the initial group of compounds synthesized by our research
group. Tested compounds contain p-fluoroaniline (16), p-methoxyaniline (17), p-ethoxyaniline (18)
and aniline (19) in the side chains. Selected 3D structures of enzymes COX-2 (3NT1) and 5-LOX
(6NCF) were taken from PDB database. MAKE Receptor 3.2.0.2 software (OpenEye Scientific Software,
Inc, Santa Fe, NM, United States) was used for preparation of enzymes’ active sites, while ligands
were prepared in OMEGA 2.5.1.4. FRED 3.2.0.2 software (OpenEye Scientific Software, Inc, Santa
Fe, NM, United States) was employed for the analysis of binding poses into enzymes’ active sites.
All tested compounds showed key binding interactions with both enzymes. The highest number
of key binding interactions was observed during molecular fitting of derivative 19 into the active
site of COX-2 and derivatives 16 and 18 into the 5-LOX. Derivative 17 had the lowest value of free
binding energy for both target enzymes (−14.90 kcal/mol for COX-2 and −9.57 kcal/mol for 5-LOX).
Therefore, all analyzed compounds represent potential dual inhibitors of mentioned enzymes.",
publisher = "MDPI",
journal = "Medical Sciences Forum",
title = "Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity",
volume = "14",
number = "1",
doi = "10.3390/ECMC2022-13279"
}

Nedeljković, N., Dobričić, V., Mijajlović, M., Vujić, Z.,& Nikolić, M.. (2022). Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity. in Medical Sciences Forum
MDPI., 14(1).
https://doi.org/10.3390/ECMC2022-13279

Nedeljković N, Dobričić V, Mijajlović M, Vujić Z, Nikolić M. Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity. in Medical Sciences Forum. 2022;14(1).
doi:10.3390/ECMC2022-13279 .

Nedeljković, Nikola, Dobričić, Vladimir, Mijajlović, Marina, Vujić, Zorica, Nikolić, Miloš, "Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity" in Medical Sciences Forum, 14, no. 1 (2022),
https://doi.org/10.3390/ECMC2022-13279 . .

TY  - CONF
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Mijajlović, Marina
AU  - Radić, Gordana
AU  - Nikolić, Miloš
AU  - Stanković, Ana
AU  - Vujić, Zorica
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5474
AB  - Masking the carboxyl group of naproxen with other functional groups may be a
promising strategy to decrease its gastrointestinal toxicity. Thiourea moiety has been described
as an important pharmacophore in a variety of pharmacologically active compounds, including
anti-inflammatory, antiviral, anticancer, hypoglycemic and antimicrobial agents. Our research
group has previously designed twenty novel thiourea derivatives of naproxen, containing amino
acids (glycine, L-alanine, β-alanine, L-valine and L-phenylalanine - compounds 1,2,3,4 and 5,
respectively), their methyl (6-10) and ethyl esters (11-15), as well as aromatic amines (16-20).
Pharmacokinetic properties and druglikeness of these compounds were predicted using
SwissADME web tool (http://www.swissadme.ch/). Predicted pharmacokinetic properties
include potential for gastrointestinal absorption, blood-brain barrier permeability, skin
permeability, transport mediated by P-glycoproteins and enzyme inhibitory potential.
Druglikeness was evaluated using Lipinski’s, Ghose’s, Veber’s, Egan’s and Muegge’s rules, as
well as on the basis of bioavailability score. All tested compounds had high-predicted
gastrointestinal absorption and low blood-brain barrier permeability. Also, derivatives 2, 4, 7,
9, 10, 12, 14, 15 and 18 were predicted to be substrates for P-glycoprotein. Derivatives with
aromatic amines (16-20) showed inhibitory potential against all tested CYP isoforms.
Derivative 19 had the highest, while derivative 13 demonstrated the lowest predicted skin
permeability. Finally, derivatives 1-12, except 5 and 10, have druglike structures, since they
obey to all imposed rules.
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings
T1  - In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen
SP  - 371
EP  - 374
DO  - 10.46793/ICCBI21.371N
ER  - 

@conference{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Mijajlović, Marina and Radić, Gordana and Nikolić, Miloš and Stanković, Ana and Vujić, Zorica",
year = "2021",
abstract = "Masking the carboxyl group of naproxen with other functional groups may be a
promising strategy to decrease its gastrointestinal toxicity. Thiourea moiety has been described
as an important pharmacophore in a variety of pharmacologically active compounds, including
anti-inflammatory, antiviral, anticancer, hypoglycemic and antimicrobial agents. Our research
group has previously designed twenty novel thiourea derivatives of naproxen, containing amino
acids (glycine, L-alanine, β-alanine, L-valine and L-phenylalanine - compounds 1,2,3,4 and 5,
respectively), their methyl (6-10) and ethyl esters (11-15), as well as aromatic amines (16-20).
Pharmacokinetic properties and druglikeness of these compounds were predicted using
SwissADME web tool (http://www.swissadme.ch/). Predicted pharmacokinetic properties
include potential for gastrointestinal absorption, blood-brain barrier permeability, skin
permeability, transport mediated by P-glycoproteins and enzyme inhibitory potential.
Druglikeness was evaluated using Lipinski’s, Ghose’s, Veber’s, Egan’s and Muegge’s rules, as
well as on the basis of bioavailability score. All tested compounds had high-predicted
gastrointestinal absorption and low blood-brain barrier permeability. Also, derivatives 2, 4, 7,
9, 10, 12, 14, 15 and 18 were predicted to be substrates for P-glycoprotein. Derivatives with
aromatic amines (16-20) showed inhibitory potential against all tested CYP isoforms.
Derivative 19 had the highest, while derivative 13 demonstrated the lowest predicted skin
permeability. Finally, derivatives 1-12, except 5 and 10, have druglike structures, since they
obey to all imposed rules.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings",
title = "In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen",
pages = "371-374",
doi = "10.46793/ICCBI21.371N"
}

Nedeljković, N., Dobričić, V., Mijajlović, M., Radić, G., Nikolić, M., Stanković, A.,& Vujić, Z.. (2021). In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen. in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings
Institute for Information Technologies, University of Kragujevac, Serbia., 371-374.
https://doi.org/10.46793/ICCBI21.371N

Nedeljković N, Dobričić V, Mijajlović M, Radić G, Nikolić M, Stanković A, Vujić Z. In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen. in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings. 2021;:371-374.
doi:10.46793/ICCBI21.371N .

Nedeljković, Nikola, Dobričić, Vladimir, Mijajlović, Marina, Radić, Gordana, Nikolić, Miloš, Stanković, Ana, Vujić, Zorica, "In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen" in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings (2021):371-374,
https://doi.org/10.46793/ICCBI21.371N . .

TY  - CONF
AU  - Dobričić, Vladimir
AU  - Nedeljković, Nikola
AU  - Mijajlović, Marina
AU  - Radić, Gordana
AU  - Nikolić, Miloš
AU  - Vujić, Zorica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5472
AB  - In the search for potent biologically active molecules, thiourea and other structure-related derivatives such as
thiosemicarbazones have attracted great attention. In the past two decades, thiourea derivatives have been recognized as
promising class of anticancer drugs due to their inhibitory activity against various targets, such as protein kinases and
topoisomerases [1,2]. In this work, molecular docking analyses were performed on 20 thiourea derivatives of naproxen,
previously designed by our group, in order to find their potential mechanisms of action. Designed derivatives contain amino
acids and aromatic amines in the side chains. Following 3D structures of selected protein kinases involved in multidrug
resistance were taken from PDB: 1M17 (EGFR), 3E87 (AKT2), 3HNG (VEGFR1) and 4JSV (mTOR). The receptor sites
were prepared using MAKE Receptor 3.2.0.2 software [3]. Ligands were prepared in OMEGA 2.5.1.4 [4,5] and
multiconformational binary files were generated. The FRED 3.2.0.2 software [6-8] was used for the analysis of binding
poses into the receptor sites. The key binding interactions were observed for derivatives 1 (with AKT2 and mTor) and 20
(with EGFR and VEGFR1). Therefore, these derivatives possess the best multitarget potential and represent potential
candidates for targeting multidrug resistant tumors (Figure 1).
PB  - COST Action 17104 (STRATAGEM)
C3  - STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia
T1  - Design of novel thiourea derivatives of naproxen with potential antitumor activity
SP  - 37
EP  - 37
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5472
ER  - 

@conference{
author = "Dobričić, Vladimir and Nedeljković, Nikola and Mijajlović, Marina and Radić, Gordana and Nikolić, Miloš and Vujić, Zorica",
year = "2020",
abstract = "In the search for potent biologically active molecules, thiourea and other structure-related derivatives such as
thiosemicarbazones have attracted great attention. In the past two decades, thiourea derivatives have been recognized as
promising class of anticancer drugs due to their inhibitory activity against various targets, such as protein kinases and
topoisomerases [1,2]. In this work, molecular docking analyses were performed on 20 thiourea derivatives of naproxen,
previously designed by our group, in order to find their potential mechanisms of action. Designed derivatives contain amino
acids and aromatic amines in the side chains. Following 3D structures of selected protein kinases involved in multidrug
resistance were taken from PDB: 1M17 (EGFR), 3E87 (AKT2), 3HNG (VEGFR1) and 4JSV (mTOR). The receptor sites
were prepared using MAKE Receptor 3.2.0.2 software [3]. Ligands were prepared in OMEGA 2.5.1.4 [4,5] and
multiconformational binary files were generated. The FRED 3.2.0.2 software [6-8] was used for the analysis of binding
poses into the receptor sites. The key binding interactions were observed for derivatives 1 (with AKT2 and mTor) and 20
(with EGFR and VEGFR1). Therefore, these derivatives possess the best multitarget potential and represent potential
candidates for targeting multidrug resistant tumors (Figure 1).",
publisher = "COST Action 17104 (STRATAGEM)",
journal = "STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia",
title = "Design of novel thiourea derivatives of naproxen with potential antitumor activity",
pages = "37-37",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5472"
}

Dobričić, V., Nedeljković, N., Mijajlović, M., Radić, G., Nikolić, M.,& Vujić, Z.. (2020). Design of novel thiourea derivatives of naproxen with potential antitumor activity. in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia
COST Action 17104 (STRATAGEM)., 37-37.
https://hdl.handle.net/21.15107/rcub_farfar_5472

Dobričić V, Nedeljković N, Mijajlović M, Radić G, Nikolić M, Vujić Z. Design of novel thiourea derivatives of naproxen with potential antitumor activity. in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia. 2020;:37-37.
https://hdl.handle.net/21.15107/rcub_farfar_5472 .

Dobričić, Vladimir, Nedeljković, Nikola, Mijajlović, Marina, Radić, Gordana, Nikolić, Miloš, Vujić, Zorica, "Design of novel thiourea derivatives of naproxen with potential antitumor activity" in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia (2020):37-37,
https://hdl.handle.net/21.15107/rcub_farfar_5472 .

TY  - JOUR
AU  - Popović, Višnja
AU  - Stojković, Dejan
AU  - Nikolić, Miloš
AU  - Heyerick, Arne
AU  - Petrović, Silvana
AU  - Soković, Marina
AU  - Niketić, Marjan
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2422
AB  - Antimicrobial properties of extracts of underground parts of three Laserpitium L. (Apiaceae) species, namely Laserpitium latifolium L., Laserpitium zernyi Hayek and Laserpitium ochridanum Micevski, were investigated. The investigated species are widely used as functional foods, as spices and for preparations in traditional medicine for treating complaints connected with infection and inflammation. Furthermore, antimicrobial and antibiofilm effects of laserpitine, the most abundant compound in the chloroform extract of Laserpitium latifolium, and guaianolide sesquiterpene lactones, such as, isomontanolide, montanolide and tarolide, principal components of the extracts of Laserpitium zernyi and Laserpitium ochridanum were assessed. The antimicrobial activity was tested using the microdilution method against five pathogenic bacteria and five fungi, as well as in the microplate biofilm assay on two Candida clinical isolates (C. albicans and C. krusei). Among the extracts, Laserpitium latifolium showed the most prominent activity. Isolated metabolites exerted higher effects against fungal than against bacterial strains, isomontanolide being the most active. Interestingly, all constituents showed higher potential on inhibition of biofilm formation than fluconazole, a reference compound. Tested metabolites may be good novel agents with high antifungal and antibacterial potential that might find practical applications in food industry as food preservatives in order to retard the growth of food spoiling microbes, but only after detailed safety assessments.
PB  - Royal Soc Chemistry, Cambridge
T2  - Food & Function
T1  - Extracts of three Laserpitium L. species and their principal components laserpitine and sesquiterpene lactones inhibit microbial growth and biofilm formation by oral Candida isolates
VL  - 6
IS  - 4
SP  - 1205
EP  - 1211
DO  - 10.1039/c5fo00066a
ER  - 

@article{
author = "Popović, Višnja and Stojković, Dejan and Nikolić, Miloš and Heyerick, Arne and Petrović, Silvana and Soković, Marina and Niketić, Marjan",
year = "2015",
abstract = "Antimicrobial properties of extracts of underground parts of three Laserpitium L. (Apiaceae) species, namely Laserpitium latifolium L., Laserpitium zernyi Hayek and Laserpitium ochridanum Micevski, were investigated. The investigated species are widely used as functional foods, as spices and for preparations in traditional medicine for treating complaints connected with infection and inflammation. Furthermore, antimicrobial and antibiofilm effects of laserpitine, the most abundant compound in the chloroform extract of Laserpitium latifolium, and guaianolide sesquiterpene lactones, such as, isomontanolide, montanolide and tarolide, principal components of the extracts of Laserpitium zernyi and Laserpitium ochridanum were assessed. The antimicrobial activity was tested using the microdilution method against five pathogenic bacteria and five fungi, as well as in the microplate biofilm assay on two Candida clinical isolates (C. albicans and C. krusei). Among the extracts, Laserpitium latifolium showed the most prominent activity. Isolated metabolites exerted higher effects against fungal than against bacterial strains, isomontanolide being the most active. Interestingly, all constituents showed higher potential on inhibition of biofilm formation than fluconazole, a reference compound. Tested metabolites may be good novel agents with high antifungal and antibacterial potential that might find practical applications in food industry as food preservatives in order to retard the growth of food spoiling microbes, but only after detailed safety assessments.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Food & Function",
title = "Extracts of three Laserpitium L. species and their principal components laserpitine and sesquiterpene lactones inhibit microbial growth and biofilm formation by oral Candida isolates",
volume = "6",
number = "4",
pages = "1205-1211",
doi = "10.1039/c5fo00066a"
}

Popović, V., Stojković, D., Nikolić, M., Heyerick, A., Petrović, S., Soković, M.,& Niketić, M.. (2015). Extracts of three Laserpitium L. species and their principal components laserpitine and sesquiterpene lactones inhibit microbial growth and biofilm formation by oral Candida isolates. in Food & Function
Royal Soc Chemistry, Cambridge., 6(4), 1205-1211.
https://doi.org/10.1039/c5fo00066a

Popović V, Stojković D, Nikolić M, Heyerick A, Petrović S, Soković M, Niketić M. Extracts of three Laserpitium L. species and their principal components laserpitine and sesquiterpene lactones inhibit microbial growth and biofilm formation by oral Candida isolates. in Food & Function. 2015;6(4):1205-1211.
doi:10.1039/c5fo00066a .

Popović, Višnja, Stojković, Dejan, Nikolić, Miloš, Heyerick, Arne, Petrović, Silvana, Soković, Marina, Niketić, Marjan, "Extracts of three Laserpitium L. species and their principal components laserpitine and sesquiterpene lactones inhibit microbial growth and biofilm formation by oral Candida isolates" in Food & Function, 6, no. 4 (2015):1205-1211,
https://doi.org/10.1039/c5fo00066a . .