TY  - CONF
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Vesović, Marina
AU  - Živanović, Ana
AU  - Radić, Gordana
AU  - Vujić, Zorica
AU  - Nikolić, Miloš
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5475
AB  - Design of dual COX-2/5-LOX inhibitors can be considered an adequate approach in the development of new anti-inflammatory drugs with less pronounced side effects. The aim of the present research was to examine the binding potential of the seven newly designed thiourea derivatives of naproxen towards COX-2 and 5-LOX. The binding analysis of ligand conformations was performed by OEDocking 3.2.0.2 software. The binding potential assessment revealed that thiourea derivatives of naproxen exhibited a comparable binding affinity as naproxen towards COX-2. The highest number of key binding interactions with 5-LOX was formed by compound 5, whereas compound 6 established the most stable complex (-9.29 kcal/mol). According to the obtained results, derivatives 5 and 6 can be considered as dual COX-2/5-LOX inhibitors with potential anti-inflammatory activity. However, none of the investigated compounds were able to form three hydrogen bonds with the binding site of COX-2, as well as three key hydrogen bonds with the active site of 5-LOX.
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 2nd International Conference on Chemo and BioInformatics ICCBIKG 2023, September 28 - 29th, 2023, Kragujevac, Serbia, Book of Proceedings
T1  - In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen
SP  - 475
EP  - 478
DO  - 10.46793/ICCBI23.475N
ER  - 

@conference{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Vesović, Marina and Živanović, Ana and Radić, Gordana and Vujić, Zorica and Nikolić, Miloš",
year = "2023",
abstract = "Design of dual COX-2/5-LOX inhibitors can be considered an adequate approach in the development of new anti-inflammatory drugs with less pronounced side effects. The aim of the present research was to examine the binding potential of the seven newly designed thiourea derivatives of naproxen towards COX-2 and 5-LOX. The binding analysis of ligand conformations was performed by OEDocking 3.2.0.2 software. The binding potential assessment revealed that thiourea derivatives of naproxen exhibited a comparable binding affinity as naproxen towards COX-2. The highest number of key binding interactions with 5-LOX was formed by compound 5, whereas compound 6 established the most stable complex (-9.29 kcal/mol). According to the obtained results, derivatives 5 and 6 can be considered as dual COX-2/5-LOX inhibitors with potential anti-inflammatory activity. However, none of the investigated compounds were able to form three hydrogen bonds with the binding site of COX-2, as well as three key hydrogen bonds with the active site of 5-LOX.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "2nd International Conference on Chemo and BioInformatics ICCBIKG 2023, September 28 - 29th, 2023, Kragujevac, Serbia, Book of Proceedings",
title = "In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen",
pages = "475-478",
doi = "10.46793/ICCBI23.475N"
}

Nedeljković, N., Dobričić, V., Vesović, M., Živanović, A., Radić, G., Vujić, Z.,& Nikolić, M.. (2023). In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen. in 2nd International Conference on Chemo and BioInformatics ICCBIKG 2023, September 28 - 29th, 2023, Kragujevac, Serbia, Book of Proceedings
Institute for Information Technologies, University of Kragujevac, Serbia., 475-478.
https://doi.org/10.46793/ICCBI23.475N

Nedeljković N, Dobričić V, Vesović M, Živanović A, Radić G, Vujić Z, Nikolić M. In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen. in 2nd International Conference on Chemo and BioInformatics ICCBIKG 2023, September 28 - 29th, 2023, Kragujevac, Serbia, Book of Proceedings. 2023;:475-478.
doi:10.46793/ICCBI23.475N .

Nedeljković, Nikola, Dobričić, Vladimir, Vesović, Marina, Živanović, Ana, Radić, Gordana, Vujić, Zorica, Nikolić, Miloš, "In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen" in 2nd International Conference on Chemo and BioInformatics ICCBIKG 2023, September 28 - 29th, 2023, Kragujevac, Serbia, Book of Proceedings (2023):475-478,
https://doi.org/10.46793/ICCBI23.475N . .

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 .