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  - JOUR
AU  - Pešić, Deniel
AU  - Đukić, Mirjana
AU  - Stanojević, Ivan
AU  - Živković, Vladimir
AU  - Bolevich, Sergey
AU  - Bolevich, Stefani
AU  - Jakovljević, Vladimir
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5559
AB  - Background: The influence of homeostatically regulated physiological processes, including cardiorespiratory fitness (VO2max), on the response to physical stressors such as acclimatisation and marching, remains understudied. We aimed to investigate the effects of summer and winter acclimatisation and marching on cortisol levels and blood lactate, to gain insight into the role of these physiological processes in the stress response. Methods: Two groups of young Europeans, classified as poor (PCF; n=9) and good physical condition (GCF; n=21), based on a VO2max threshold of 40 mL O2/ kg/min, underwent 2-h march (6–7 km/h) in winter (5 ∘C) and summer (32 ∘C). Commercial tests, UniCel DxI Access Cortisol assay and EKF Biosen Clinic/GP assay were used for cortisol and lactate blood measurements (morning samples and those taken immediately after marches), respectively. Results: Basal cortisol levels were significantly higher at 5 °C than at 32 °C (PCF group: P=0.0079; cortisol dropped after the march at 5 °C in both groups, but increased at 32 °C only in PCF. Basal lactate levels were higher at 32 °C only in the GCF group (compared to PCF, P=0.0014) and post-marching (compared to basal values, P=0.0002). Conclusion: Cold exposure elicits a more significant stress response, based on higher basal cortisol levels, in individuals with worse physical fitness. Anaerobe metabolism prevails in participants with better physical fitness exposed to high ambient temperature based on increased basal and post-marching lactate levels. The study is significant for individual training/performance optimisation as it indicates the association between physiological stress responses and individual physical fitness levels.
AB  - Uvod: Uticaj homeostatski regulisanih fiziolo{kih procesa, uklju~uju}i kardiorespiratornu kondiciju (VO2max), na odgovor na fizi~ke stresore poput aklimatizacije i mar{i- ranja, ostaje nedovoljno prou~en. Cilj istra`ivanja je bio i da se ispita uticaj aklimatizacije i mar{iranja tokom leta i zime na nivoe kortizola i laktoze u krvi, pru`aju}i uvid u ulogu ovih fiziolo{kih procesa u odgovoru na stres. Metode: Dve grupe mladih Evropljana, klasifikovane kao osobe sa slabom (PCF; n=9) i dobrom fizi~kom kondicijom (GCF; n=21), na osnovu praga VO2max od 40 mL O 2/kg/min, su bile izlo`ene dvosatnom mar{u (6–7 km/h) u dva navrata, zimi na 5 °C i leti, na 32 °C. U uzorcima krvi (jutarnji i neposredno nakon mar{a) su odre|ivani nivoi kortizola i laktata komercijalnim testovima, UniCel DxI Access Cortisol i EKF Biosen Clinic/GP. Rezultati: Bazalni nivoi kortizola su bili zna~ajno vi{i na 5 °C nego na 32 °C (u PCF grupi: P=0,0079); nakon mar{i- ranja na 5 °C kortizol opada u obe grupe a pove}an je na 32 °C samo u PCF grupi. Bazalni nivoi laktoze bili su vi{i na 32 °C samo u GCF grupi (porede}i sa PCF grupom, P=0,0014) i nakon mar{iranja (porede}i sa bazalnim vred- nostima, P=0,0002).
PB  - Society of Medical Biochemists of Serbia
T2  - Journal of Medical Biochemistry
T1  - Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches
T1  - Kardiorespiratorni fitnes i njegov značaj u reakcijama kortizola i laktata prilikom zimskih i letnjih marševa
VL  - 43
IS  - 1
SP  - 72
EP  - 85
DO  - 10.5937/jomb0-44369
ER  - 

@article{
author = "Pešić, Deniel and Đukić, Mirjana and Stanojević, Ivan and Živković, Vladimir and Bolevich, Sergey and Bolevich, Stefani and Jakovljević, Vladimir",
year = "2024",
abstract = "Background: The influence of homeostatically regulated physiological processes, including cardiorespiratory fitness (VO2max), on the response to physical stressors such as acclimatisation and marching, remains understudied. We aimed to investigate the effects of summer and winter acclimatisation and marching on cortisol levels and blood lactate, to gain insight into the role of these physiological processes in the stress response. Methods: Two groups of young Europeans, classified as poor (PCF; n=9) and good physical condition (GCF; n=21), based on a VO2max threshold of 40 mL O2/ kg/min, underwent 2-h march (6–7 km/h) in winter (5 ∘C) and summer (32 ∘C). Commercial tests, UniCel DxI Access Cortisol assay and EKF Biosen Clinic/GP assay were used for cortisol and lactate blood measurements (morning samples and those taken immediately after marches), respectively. Results: Basal cortisol levels were significantly higher at 5 °C than at 32 °C (PCF group: P=0.0079; cortisol dropped after the march at 5 °C in both groups, but increased at 32 °C only in PCF. Basal lactate levels were higher at 32 °C only in the GCF group (compared to PCF, P=0.0014) and post-marching (compared to basal values, P=0.0002). Conclusion: Cold exposure elicits a more significant stress response, based on higher basal cortisol levels, in individuals with worse physical fitness. Anaerobe metabolism prevails in participants with better physical fitness exposed to high ambient temperature based on increased basal and post-marching lactate levels. The study is significant for individual training/performance optimisation as it indicates the association between physiological stress responses and individual physical fitness levels., Uvod: Uticaj homeostatski regulisanih fiziolo{kih procesa, uklju~uju}i kardiorespiratornu kondiciju (VO2max), na odgovor na fizi~ke stresore poput aklimatizacije i mar{i- ranja, ostaje nedovoljno prou~en. Cilj istra`ivanja je bio i da se ispita uticaj aklimatizacije i mar{iranja tokom leta i zime na nivoe kortizola i laktoze u krvi, pru`aju}i uvid u ulogu ovih fiziolo{kih procesa u odgovoru na stres. Metode: Dve grupe mladih Evropljana, klasifikovane kao osobe sa slabom (PCF; n=9) i dobrom fizi~kom kondicijom (GCF; n=21), na osnovu praga VO2max od 40 mL O 2/kg/min, su bile izlo`ene dvosatnom mar{u (6–7 km/h) u dva navrata, zimi na 5 °C i leti, na 32 °C. U uzorcima krvi (jutarnji i neposredno nakon mar{a) su odre|ivani nivoi kortizola i laktata komercijalnim testovima, UniCel DxI Access Cortisol i EKF Biosen Clinic/GP. Rezultati: Bazalni nivoi kortizola su bili zna~ajno vi{i na 5 °C nego na 32 °C (u PCF grupi: P=0,0079); nakon mar{i- ranja na 5 °C kortizol opada u obe grupe a pove}an je na 32 °C samo u PCF grupi. Bazalni nivoi laktoze bili su vi{i na 32 °C samo u GCF grupi (porede}i sa PCF grupom, P=0,0014) i nakon mar{iranja (porede}i sa bazalnim vred- nostima, P=0,0002).",
publisher = "Society of Medical Biochemists of Serbia",
journal = "Journal of Medical Biochemistry",
title = "Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches, Kardiorespiratorni fitnes i njegov značaj u reakcijama kortizola i laktata prilikom zimskih i letnjih marševa",
volume = "43",
number = "1",
pages = "72-85",
doi = "10.5937/jomb0-44369"
}

Pešić, D., Đukić, M., Stanojević, I., Živković, V., Bolevich, S., Bolevich, S.,& Jakovljević, V.. (2024). Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches. in Journal of Medical Biochemistry
Society of Medical Biochemists of Serbia., 43(1), 72-85.
https://doi.org/10.5937/jomb0-44369

Pešić D, Đukić M, Stanojević I, Živković V, Bolevich S, Bolevich S, Jakovljević V. Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches. in Journal of Medical Biochemistry. 2024;43(1):72-85.
doi:10.5937/jomb0-44369 .

Pešić, Deniel, Đukić, Mirjana, Stanojević, Ivan, Živković, Vladimir, Bolevich, Sergey, Bolevich, Stefani, Jakovljević, Vladimir, "Cardiorespiratory fitness mediates cortisol and lactate responses to winter and summer marches" in Journal of Medical Biochemistry, 43, no. 1 (2024):72-85,
https://doi.org/10.5937/jomb0-44369 . .

TY  - JOUR
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Bošković, Jelena
AU  - Vesović, Marina
AU  - Bradić, Jovana
AU  - Anđić, Marijana
AU  - Kočović, Aleksandar
AU  - Jeremić, Nevena
AU  - Novaković, Jovana
AU  - Jakovljević, Vladimir
AU  - Vujić, Zorica
AU  - Nikolić, Miloš
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4756
AB  - The aim of the study was a synthesis and investigation of the dose-dependent anti-inflammatory effect of new thiourea derivatives of naproxen with selected aromatic amines and esters of aromatic amino acids. The results of the in vivo study indicate that derivatives of m-anisidine (4) and N-methyl tryptophan methyl ester (7) showed the most potent anti-inflammatory activity four hours after injection of carrageenan, with the percentage of inhibition of 54.01% and 54.12%, respectively. In vitro assays of COX-2 inhibition demonstrated that none of the tested compounds achieved 50% inhibition at concentrations lower than 100 µM. On the other hand, the aromatic amine derivatives (1–5) accomplished significant inhibition of 5-LOX, and the lowest IC50 value was observed for compound 4 (0.30 μM). High anti-edematous activity of compound 4 in the rat paw edema model, together with potent inhibition of 5-LOX, highlight this compound as a promising anti-inflammatory agent
PB  - MDPI
T2  - Pharmaceuticals
T1  - Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen
VL  - 16
IS  - 5
DO  - 10.3390/ph16050666
ER  - 

@article{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Bošković, Jelena and Vesović, Marina and Bradić, Jovana and Anđić, Marijana and Kočović, Aleksandar and Jeremić, Nevena and Novaković, Jovana and Jakovljević, Vladimir and Vujić, Zorica and Nikolić, Miloš",
year = "2023",
abstract = "The aim of the study was a synthesis and investigation of the dose-dependent anti-inflammatory effect of new thiourea derivatives of naproxen with selected aromatic amines and esters of aromatic amino acids. The results of the in vivo study indicate that derivatives of m-anisidine (4) and N-methyl tryptophan methyl ester (7) showed the most potent anti-inflammatory activity four hours after injection of carrageenan, with the percentage of inhibition of 54.01% and 54.12%, respectively. In vitro assays of COX-2 inhibition demonstrated that none of the tested compounds achieved 50% inhibition at concentrations lower than 100 µM. On the other hand, the aromatic amine derivatives (1–5) accomplished significant inhibition of 5-LOX, and the lowest IC50 value was observed for compound 4 (0.30 μM). High anti-edematous activity of compound 4 in the rat paw edema model, together with potent inhibition of 5-LOX, highlight this compound as a promising anti-inflammatory agent",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen",
volume = "16",
number = "5",
doi = "10.3390/ph16050666"
}

Nedeljković, N., Dobričić, V., Bošković, J., Vesović, M., Bradić, J., Anđić, M., Kočović, A., Jeremić, N., Novaković, J., Jakovljević, V., Vujić, Z.,& Nikolić, M.. (2023). Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen. in Pharmaceuticals
MDPI., 16(5).
https://doi.org/10.3390/ph16050666

Nedeljković N, Dobričić V, Bošković J, Vesović M, Bradić J, Anđić M, Kočović A, Jeremić N, Novaković J, Jakovljević V, Vujić Z, Nikolić M. Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen. in Pharmaceuticals. 2023;16(5).
doi:10.3390/ph16050666 .

Nedeljković, Nikola, Dobričić, Vladimir, Bošković, Jelena, Vesović, Marina, Bradić, Jovana, Anđić, Marijana, Kočović, Aleksandar, Jeremić, Nevena, Novaković, Jovana, Jakovljević, Vladimir, Vujić, Zorica, Nikolić, Miloš, "Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen" in Pharmaceuticals, 16, no. 5 (2023),
https://doi.org/10.3390/ph16050666 . .

TY  - CONF
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Bošković, Jelena
AU  - Vesović, Marina
AU  - Bradić, Jovana
AU  - Anđić, Marijana
AU  - Kočović, Aleksandar
AU  - Jeremić, Nevena
AU  - Novaković, Jovana
AU  - Jakovljević, Vladimir
AU  - Vujić, Zorica
AU  - Nikolić, Miloš
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5476
AB  - The aim of the conducted study was to develop new potential dual COX-2 and 5-LOX
inhibitors based on naproxen scaffold. We performed the evaluation of in vivo and in vitro
anti-inflammatory activity of newly synthesized thiourea derivatives of naproxen containing
m-anisidine and N-methyl tryptophan methyl ester in a side chain. An in vivo study
was carried out using a carrageenan-induced paw edema model of acute inflammation.
COX-2 and 5-LOX inhibitory potential of synthesized compounds was evaluated using
fluorometric inhibitor screening kits. In silico study was performed in OEDocking 3.2.0.2
software with the FRED tool. Two investigated derivatives exhibited comparable anti-inflammatory
activity to naproxen (56.32%) four hours after injection of carrageenan, with
the percentage of inhibition being 54.01% (m-anisidine derivative) and 54.12% (N-methyl
tryptophan methyl ester derivative). In vitro studies of COX-2 inhibition demonstrated that
none of the tested compounds achieved 50% inhibition at concentrations below 100 μM,
whereas the m-anisidine derivative accomplished comparable inhibition of 5-LOX (IC50 =
0.30 μM) to commercial 5-LOX inhibitor zileuton (IC50 = 0.36 μM). Inability of the tested
compounds to form three hydrogen bonds with ARG120 and TYR355 could be a reason
why these compounds showed weak COX-2 inhibition. The m-anisidine derivative formed
a more stable complex with the 5-LOX enzyme (−8.39 kcal/mol), compared to N-methyl
tryptophan methyl ester derivative (−7.98 kcal/mol), with the absence of the iron ion chelation
in the active site in both cases. The significant in vivo anti-inflammatory activity of
the m-anisidine derivative, together with the potent inhibition of 5-LOX, highlighted this
compound as a promising anti-inflammatory agent.
PB  - Fakultet medicinskih nauka Univerziteta u Kragujevcu
C3  - 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia
T1  - Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5476
ER  - 

@conference{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Bošković, Jelena and Vesović, Marina and Bradić, Jovana and Anđić, Marijana and Kočović, Aleksandar and Jeremić, Nevena and Novaković, Jovana and Jakovljević, Vladimir and Vujić, Zorica and Nikolić, Miloš",
year = "2023",
abstract = "The aim of the conducted study was to develop new potential dual COX-2 and 5-LOX
inhibitors based on naproxen scaffold. We performed the evaluation of in vivo and in vitro
anti-inflammatory activity of newly synthesized thiourea derivatives of naproxen containing
m-anisidine and N-methyl tryptophan methyl ester in a side chain. An in vivo study
was carried out using a carrageenan-induced paw edema model of acute inflammation.
COX-2 and 5-LOX inhibitory potential of synthesized compounds was evaluated using
fluorometric inhibitor screening kits. In silico study was performed in OEDocking 3.2.0.2
software with the FRED tool. Two investigated derivatives exhibited comparable anti-inflammatory
activity to naproxen (56.32%) four hours after injection of carrageenan, with
the percentage of inhibition being 54.01% (m-anisidine derivative) and 54.12% (N-methyl
tryptophan methyl ester derivative). In vitro studies of COX-2 inhibition demonstrated that
none of the tested compounds achieved 50% inhibition at concentrations below 100 μM,
whereas the m-anisidine derivative accomplished comparable inhibition of 5-LOX (IC50 =
0.30 μM) to commercial 5-LOX inhibitor zileuton (IC50 = 0.36 μM). Inability of the tested
compounds to form three hydrogen bonds with ARG120 and TYR355 could be a reason
why these compounds showed weak COX-2 inhibition. The m-anisidine derivative formed
a more stable complex with the 5-LOX enzyme (−8.39 kcal/mol), compared to N-methyl
tryptophan methyl ester derivative (−7.98 kcal/mol), with the absence of the iron ion chelation
in the active site in both cases. The significant in vivo anti-inflammatory activity of
the m-anisidine derivative, together with the potent inhibition of 5-LOX, highlighted this
compound as a promising anti-inflammatory agent.",
publisher = "Fakultet medicinskih nauka Univerziteta u Kragujevcu",
journal = "9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia",
title = "Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5476"
}

Nedeljković, N., Dobričić, V., Bošković, J., Vesović, M., Bradić, J., Anđić, M., Kočović, A., Jeremić, N., Novaković, J., Jakovljević, V., Vujić, Z.,& Nikolić, M.. (2023). Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach. in 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia
Fakultet medicinskih nauka Univerziteta u Kragujevcu..
https://hdl.handle.net/21.15107/rcub_farfar_5476

Nedeljković N, Dobričić V, Bošković J, Vesović M, Bradić J, Anđić M, Kočović A, Jeremić N, Novaković J, Jakovljević V, Vujić Z, Nikolić M. Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach. in 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_5476 .

Nedeljković, Nikola, Dobričić, Vladimir, Bošković, Jelena, Vesović, Marina, Bradić, Jovana, Anđić, Marijana, Kočović, Aleksandar, Jeremić, Nevena, Novaković, Jovana, Jakovljević, Vladimir, Vujić, Zorica, Nikolić, Miloš, "Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach" in 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia (2023),
https://hdl.handle.net/21.15107/rcub_farfar_5476 .

TY  - JOUR
AU  - Mićović, Tijana
AU  - Katanić Stanković, Jelena S.
AU  - Bauer, Rudolf
AU  - Nöst, Xuehong
AU  - Marković, Zoran
AU  - Milenković, Dejan
AU  - Jakovljević, Vladimir
AU  - Tomović, Marina
AU  - Bradić, Jovana
AU  - Stešević, Danijela
AU  - Stojanović, Danilo
AU  - Maksimović, Zoran
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4079
AB  - Ethnopharmacological relevance: Medicinal properties of hyssop have been used in traditional medicine since ancient times, inter alia, in diseases/conditions with an inherent inflammatory process. Aim of the study: Accordingly, the aim of this study was to investigate the anti-inflammatory properties of hyssop herb preparations (essential oil and methanol extracts) in vivo, in vitro and in silico. Materials and methods: For in vitro testing of essential oils and extracts of hyssop herb, the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays were used. In vivo anti-inflammatory potential of the extracts (at doses of 50, 100 and 200 mg/kg) was assessed using the carrageenan-induced rat paw edema test. Molecular docking and dynamics were used for in silico testing of the inhibitory activity of chlorogenic (CA) and rosmarinic (RA) acids, as the dominant compounds in the tested methanol extracts against COX-1 and COX-2 enzymes. Results: Significant inhibitory activity was shown in the COX-2 test regarding extracts (essential oils did not exhibit any significant activity). Namely, all analyzed extracts, at a concentration of 20 μg/mL, showed a percentage of inhibition of COX-2 enzyme (54.04–63.04%), which did not indicate a statistically significant difference from the positive control of celecoxib (61.60%) at a concentration of 8.8 μM. In vivo testing showed that all methanol extracts of hyssop herb, at the highest test dose of 200 mg/kg in the third and fourth hours, after carrageenan administration, exhibited a statistically significant (p < 0.05) inhibitory effect on the increase in rat paw edema in relation to control. This activity is comparable or higher in relation to the reference substance, indomethacin, at a concentration of 8 mg/kg. The preliminary in silico results suggest that investigated compounds (RA and CA) showed better inhibitory activity against COX-1 and COX-2 than standard non-steroidal anti-inflammatory drug (NSAID), ibuprofen, as evident from the free binding energy (ΔGbind in kJ mol−1). The binding energies of the docked compounds to COX-1 and -2 were found to be in the range between −47.4 and −49.2 kJ mol−1. Ibuprofen, as the one NSAID, for the same receptors targets, showed remarkably higher binding energy (ΔGbind = −31.3 kJ mol−1 to COX-1, and ΔGbind = −30.9 kJ mol−1 to COX-2). Conclusion: The results obtained not only support the traditional use of hyssop herb in inflammatory conditions in folk medicine, but also open the door to and the need for further in vivo testing of extracts in order to examine the molecular mechanism of anti-inflammatory activity in living systems and possibly develop a new anti-inflammatory drug or supplement.
PB  - Elsevier Ireland Ltd
T2  - Journal of Ethnopharmacology
T1  - In vitro, in vivo and in silico evaluation of the anti-inflammatory potential of Hyssopus officinalis L. subsp. aristatus (Godr.) Nyman (Lamiaceae)
VL  - 293
DO  - 10.1016/j.jep.2022.115201
ER  - 

@article{
author = "Mićović, Tijana and Katanić Stanković, Jelena S. and Bauer, Rudolf and Nöst, Xuehong and Marković, Zoran and Milenković, Dejan and Jakovljević, Vladimir and Tomović, Marina and Bradić, Jovana and Stešević, Danijela and Stojanović, Danilo and Maksimović, Zoran",
year = "2022",
abstract = "Ethnopharmacological relevance: Medicinal properties of hyssop have been used in traditional medicine since ancient times, inter alia, in diseases/conditions with an inherent inflammatory process. Aim of the study: Accordingly, the aim of this study was to investigate the anti-inflammatory properties of hyssop herb preparations (essential oil and methanol extracts) in vivo, in vitro and in silico. Materials and methods: For in vitro testing of essential oils and extracts of hyssop herb, the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays were used. In vivo anti-inflammatory potential of the extracts (at doses of 50, 100 and 200 mg/kg) was assessed using the carrageenan-induced rat paw edema test. Molecular docking and dynamics were used for in silico testing of the inhibitory activity of chlorogenic (CA) and rosmarinic (RA) acids, as the dominant compounds in the tested methanol extracts against COX-1 and COX-2 enzymes. Results: Significant inhibitory activity was shown in the COX-2 test regarding extracts (essential oils did not exhibit any significant activity). Namely, all analyzed extracts, at a concentration of 20 μg/mL, showed a percentage of inhibition of COX-2 enzyme (54.04–63.04%), which did not indicate a statistically significant difference from the positive control of celecoxib (61.60%) at a concentration of 8.8 μM. In vivo testing showed that all methanol extracts of hyssop herb, at the highest test dose of 200 mg/kg in the third and fourth hours, after carrageenan administration, exhibited a statistically significant (p < 0.05) inhibitory effect on the increase in rat paw edema in relation to control. This activity is comparable or higher in relation to the reference substance, indomethacin, at a concentration of 8 mg/kg. The preliminary in silico results suggest that investigated compounds (RA and CA) showed better inhibitory activity against COX-1 and COX-2 than standard non-steroidal anti-inflammatory drug (NSAID), ibuprofen, as evident from the free binding energy (ΔGbind in kJ mol−1). The binding energies of the docked compounds to COX-1 and -2 were found to be in the range between −47.4 and −49.2 kJ mol−1. Ibuprofen, as the one NSAID, for the same receptors targets, showed remarkably higher binding energy (ΔGbind = −31.3 kJ mol−1 to COX-1, and ΔGbind = −30.9 kJ mol−1 to COX-2). Conclusion: The results obtained not only support the traditional use of hyssop herb in inflammatory conditions in folk medicine, but also open the door to and the need for further in vivo testing of extracts in order to examine the molecular mechanism of anti-inflammatory activity in living systems and possibly develop a new anti-inflammatory drug or supplement.",
publisher = "Elsevier Ireland Ltd",
journal = "Journal of Ethnopharmacology",
title = "In vitro, in vivo and in silico evaluation of the anti-inflammatory potential of Hyssopus officinalis L. subsp. aristatus (Godr.) Nyman (Lamiaceae)",
volume = "293",
doi = "10.1016/j.jep.2022.115201"
}

Mićović, T., Katanić Stanković, J. S., Bauer, R., Nöst, X., Marković, Z., Milenković, D., Jakovljević, V., Tomović, M., Bradić, J., Stešević, D., Stojanović, D.,& Maksimović, Z.. (2022). In vitro, in vivo and in silico evaluation of the anti-inflammatory potential of Hyssopus officinalis L. subsp. aristatus (Godr.) Nyman (Lamiaceae). in Journal of Ethnopharmacology
Elsevier Ireland Ltd., 293.
https://doi.org/10.1016/j.jep.2022.115201

Mićović T, Katanić Stanković JS, Bauer R, Nöst X, Marković Z, Milenković D, Jakovljević V, Tomović M, Bradić J, Stešević D, Stojanović D, Maksimović Z. In vitro, in vivo and in silico evaluation of the anti-inflammatory potential of Hyssopus officinalis L. subsp. aristatus (Godr.) Nyman (Lamiaceae). in Journal of Ethnopharmacology. 2022;293.
doi:10.1016/j.jep.2022.115201 .

Mićović, Tijana, Katanić Stanković, Jelena S., Bauer, Rudolf, Nöst, Xuehong, Marković, Zoran, Milenković, Dejan, Jakovljević, Vladimir, Tomović, Marina, Bradić, Jovana, Stešević, Danijela, Stojanović, Danilo, Maksimović, Zoran, "In vitro, in vivo and in silico evaluation of the anti-inflammatory potential of Hyssopus officinalis L. subsp. aristatus (Godr.) Nyman (Lamiaceae)" in Journal of Ethnopharmacology, 293 (2022),
https://doi.org/10.1016/j.jep.2022.115201 . .

TY  - JOUR
AU  - Mićović, Tijana
AU  - Topalović, Dijana
AU  - Živković, Lada
AU  - Spremo-Potparević, Biljana
AU  - Jakovljević, Vladimir
AU  - Matić, Sanja
AU  - Popović, Suzana
AU  - Baskić, Dejan
AU  - Stešević, Danijela
AU  - Samardžić, Stevan
AU  - Stojanović, Danilo
AU  - Maksimović, Zoran
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3817
AB  - Abstract:Hyssopus officinalisL. is a well-known aromatic plant used in traditional medicine and the foodand cosmetics industry. The aim of this study is to assess the antioxidant, genotoxic, antigenotoxic andcytotoxic properties of characterized hyssop essential oils and methanol extracts. Chemical compositionwas analyzed by gas chromatography - mass spectrometry (GC-MS) and liquid chromatography with diodearray detection and mass spectrometry (LC-DAD-MS), respectively. Antioxidant activity was examinedby 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) tests; genotoxicand antigenotoxic activity were examined by the comet assay, while cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide dye (MTT) test against tumor cell lines (SW480,MDA-MB 231, HeLa) and non-transformed human lung fibroblast cell lines (MRC-5). The essential oilswere rich in monoterpene hydrocarbons (e.g., limonene; 7.99–23.81%), oxygenated monoterpenes (1,8-cineole; 38.19–67.1%) and phenylpropanoids (methyl eugenol; 0.00–28.33%). In methanol extracts, the mostabundant phenolics were chlorogenic and rosmarinic acid (23.35–33.46 and 3.53–17.98 mg/g, respectively).Methanol extracts expressed moderate to weak antioxidant activity (DPPH IC50= 56.04–199.89μg/mL,FRAP = 0.667–0.959 mmol Fe2+/g). Hyssop preparations significantly reduced DNA damage in humanwhole blood cells, induced by pretreatment with hydrogen peroxide. Methanol extracts exhibited selectiveand potent dose- and time-dependent activity against the HeLa cell line.  Results of the current studydemonstrated notableH.officinalismedicinal potential, which calls for further investigation.
PB  - MDPI AG
T2  - Plants
T1  - Antioxidant, antigenotoxic and cytotoxic activity of essential oils and methanol extracts of hyssopus officinalis l. Subsp. aristatus (godr.) nyman (lamiaceae)
VL  - 10
IS  - 4
DO  - 10.3390/plants10040711
ER  - 

@article{
author = "Mićović, Tijana and Topalović, Dijana and Živković, Lada and Spremo-Potparević, Biljana and Jakovljević, Vladimir and Matić, Sanja and Popović, Suzana and Baskić, Dejan and Stešević, Danijela and Samardžić, Stevan and Stojanović, Danilo and Maksimović, Zoran",
year = "2021",
abstract = "Abstract:Hyssopus officinalisL. is a well-known aromatic plant used in traditional medicine and the foodand cosmetics industry. The aim of this study is to assess the antioxidant, genotoxic, antigenotoxic andcytotoxic properties of characterized hyssop essential oils and methanol extracts. Chemical compositionwas analyzed by gas chromatography - mass spectrometry (GC-MS) and liquid chromatography with diodearray detection and mass spectrometry (LC-DAD-MS), respectively. Antioxidant activity was examinedby 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) tests; genotoxicand antigenotoxic activity were examined by the comet assay, while cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide dye (MTT) test against tumor cell lines (SW480,MDA-MB 231, HeLa) and non-transformed human lung fibroblast cell lines (MRC-5). The essential oilswere rich in monoterpene hydrocarbons (e.g., limonene; 7.99–23.81%), oxygenated monoterpenes (1,8-cineole; 38.19–67.1%) and phenylpropanoids (methyl eugenol; 0.00–28.33%). In methanol extracts, the mostabundant phenolics were chlorogenic and rosmarinic acid (23.35–33.46 and 3.53–17.98 mg/g, respectively).Methanol extracts expressed moderate to weak antioxidant activity (DPPH IC50= 56.04–199.89μg/mL,FRAP = 0.667–0.959 mmol Fe2+/g). Hyssop preparations significantly reduced DNA damage in humanwhole blood cells, induced by pretreatment with hydrogen peroxide. Methanol extracts exhibited selectiveand potent dose- and time-dependent activity against the HeLa cell line.  Results of the current studydemonstrated notableH.officinalismedicinal potential, which calls for further investigation.",
publisher = "MDPI AG",
journal = "Plants",
title = "Antioxidant, antigenotoxic and cytotoxic activity of essential oils and methanol extracts of hyssopus officinalis l. Subsp. aristatus (godr.) nyman (lamiaceae)",
volume = "10",
number = "4",
doi = "10.3390/plants10040711"
}

Mićović, T., Topalović, D., Živković, L., Spremo-Potparević, B., Jakovljević, V., Matić, S., Popović, S., Baskić, D., Stešević, D., Samardžić, S., Stojanović, D.,& Maksimović, Z.. (2021). Antioxidant, antigenotoxic and cytotoxic activity of essential oils and methanol extracts of hyssopus officinalis l. Subsp. aristatus (godr.) nyman (lamiaceae). in Plants
MDPI AG., 10(4).
https://doi.org/10.3390/plants10040711

Mićović T, Topalović D, Živković L, Spremo-Potparević B, Jakovljević V, Matić S, Popović S, Baskić D, Stešević D, Samardžić S, Stojanović D, Maksimović Z. Antioxidant, antigenotoxic and cytotoxic activity of essential oils and methanol extracts of hyssopus officinalis l. Subsp. aristatus (godr.) nyman (lamiaceae). in Plants. 2021;10(4).
doi:10.3390/plants10040711 .

Mićović, Tijana, Topalović, Dijana, Živković, Lada, Spremo-Potparević, Biljana, Jakovljević, Vladimir, Matić, Sanja, Popović, Suzana, Baskić, Dejan, Stešević, Danijela, Samardžić, Stevan, Stojanović, Danilo, Maksimović, Zoran, "Antioxidant, antigenotoxic and cytotoxic activity of essential oils and methanol extracts of hyssopus officinalis l. Subsp. aristatus (godr.) nyman (lamiaceae)" in Plants, 10, no. 4 (2021),
https://doi.org/10.3390/plants10040711 . .

TY  - CONF
AU  - Lakić, Dragana
AU  - Odalović, Marina
AU  - Jakovljević, Vladimir
AU  - Arsić, Ivana A.
AU  - Komazec, Zoran
AU  - Tasić, Ljiljana
AU  - Parojčić, Jelena
AU  - Cavaco, Afonso
AU  - Henman, Martin
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3179
PB  - Springer
C3  - International Journal of Clinical Pharmacy
T1  - Advancement in pharmacy education-professional practice in university curricula in Serbia
VL  - 40
IS  - 1
SP  - 242
EP  - 243
DO  - 10.1007/s11096-017-0565-9
ER  - 

@conference{
author = "Lakić, Dragana and Odalović, Marina and Jakovljević, Vladimir and Arsić, Ivana A. and Komazec, Zoran and Tasić, Ljiljana and Parojčić, Jelena and Cavaco, Afonso and Henman, Martin",
year = "2018",
publisher = "Springer",
journal = "International Journal of Clinical Pharmacy",
title = "Advancement in pharmacy education-professional practice in university curricula in Serbia",
volume = "40",
number = "1",
pages = "242-243",
doi = "10.1007/s11096-017-0565-9"
}

Lakić, D., Odalović, M., Jakovljević, V., Arsić, I. A., Komazec, Z., Tasić, L., Parojčić, J., Cavaco, A.,& Henman, M.. (2018). Advancement in pharmacy education-professional practice in university curricula in Serbia. in International Journal of Clinical Pharmacy
Springer., 40(1), 242-243.
https://doi.org/10.1007/s11096-017-0565-9

Lakić D, Odalović M, Jakovljević V, Arsić IA, Komazec Z, Tasić L, Parojčić J, Cavaco A, Henman M. Advancement in pharmacy education-professional practice in university curricula in Serbia. in International Journal of Clinical Pharmacy. 2018;40(1):242-243.
doi:10.1007/s11096-017-0565-9 .

Lakić, Dragana, Odalović, Marina, Jakovljević, Vladimir, Arsić, Ivana A., Komazec, Zoran, Tasić, Ljiljana, Parojčić, Jelena, Cavaco, Afonso, Henman, Martin, "Advancement in pharmacy education-professional practice in university curricula in Serbia" in International Journal of Clinical Pharmacy, 40, no. 1 (2018):242-243,
https://doi.org/10.1007/s11096-017-0565-9 . .