TY  - JOUR
AU  - Milović, Emilija
AU  - Petronijević, Jelena
AU  - Joksimović, Nenad
AU  - Beljkaš, Milan
AU  - Ružić, Dušan
AU  - Nikolić, Katarina
AU  - Vraneš, Milan
AU  - Tot, Aleksandar
AU  - Đorđić Crnogorac, Marija
AU  - Stanojković, Tatjana
AU  - Janković, Nenad
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4058
AB  - Selected tetrahydropyrimidines (THPMs) were investigated by means of cytotoxic activities on selected cancer (HeLa, A549, and LS174) and non-cancerous cell lines (MRC-5). Among evaluated compounds, two of them ( B7 and B8 ) showed good cytotoxic activity on the tested cell lines and were selected for fur- ther evaluation that included mechanism of action, DNA and BSA interactions and molecular docking study. Calculated parameters from fluorescence quenching studies indicated that B7 and B8 bind on mi- nor groove of DNA and have great ability to bind on carrier protein. Three-dimensional quantitative struc- ture anti-HeLa activity study was performed with data set of THPMs. Molecular Interaction Fields were used to derive Grid independent descriptors (GRIND), as independent variables in Pentacle software. The quality and predictive capacity of the model was proved by internal statistical parameters: R 2 = 0.992, Q 2 = 0.51, as well as external parameters such as R 2 pred = 0.804 and r m 2 , r / 2 m and r 2 m , that were higher than 0.5. The structural determinants significant for anti-HeLa activity of compounds were identified by using developed 3D-QSAR model. Interpretation of the most impactful GRIND variables on the anti-HeLa activity generated several hypotheses for design of novel and more potent anti-HeLa tetrahydropyrim- idines. Additional molecular targets for the most active synthesized derivatives ( B7 and B8 ) are predicted by use of online web-based tool-SwissTargetPrediction.
PB  - Elsevier B.V.
T2  - Journal of Molecular Structure
T1  - Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions
VL  - 1257
DO  - 10.1016/j.molstruc.2022.132621
ER  - 

@article{
author = "Milović, Emilija and Petronijević, Jelena and Joksimović, Nenad and Beljkaš, Milan and Ružić, Dušan and Nikolić, Katarina and Vraneš, Milan and Tot, Aleksandar and Đorđić Crnogorac, Marija and Stanojković, Tatjana and Janković, Nenad",
year = "2022",
abstract = "Selected tetrahydropyrimidines (THPMs) were investigated by means of cytotoxic activities on selected cancer (HeLa, A549, and LS174) and non-cancerous cell lines (MRC-5). Among evaluated compounds, two of them ( B7 and B8 ) showed good cytotoxic activity on the tested cell lines and were selected for fur- ther evaluation that included mechanism of action, DNA and BSA interactions and molecular docking study. Calculated parameters from fluorescence quenching studies indicated that B7 and B8 bind on mi- nor groove of DNA and have great ability to bind on carrier protein. Three-dimensional quantitative struc- ture anti-HeLa activity study was performed with data set of THPMs. Molecular Interaction Fields were used to derive Grid independent descriptors (GRIND), as independent variables in Pentacle software. The quality and predictive capacity of the model was proved by internal statistical parameters: R 2 = 0.992, Q 2 = 0.51, as well as external parameters such as R 2 pred = 0.804 and r m 2 , r / 2 m and r 2 m , that were higher than 0.5. The structural determinants significant for anti-HeLa activity of compounds were identified by using developed 3D-QSAR model. Interpretation of the most impactful GRIND variables on the anti-HeLa activity generated several hypotheses for design of novel and more potent anti-HeLa tetrahydropyrim- idines. Additional molecular targets for the most active synthesized derivatives ( B7 and B8 ) are predicted by use of online web-based tool-SwissTargetPrediction.",
publisher = "Elsevier B.V.",
journal = "Journal of Molecular Structure",
title = "Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions",
volume = "1257",
doi = "10.1016/j.molstruc.2022.132621"
}

Milović, E., Petronijević, J., Joksimović, N., Beljkaš, M., Ružić, D., Nikolić, K., Vraneš, M., Tot, A., Đorđić Crnogorac, M., Stanojković, T.,& Janković, N.. (2022). Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions. in Journal of Molecular Structure
Elsevier B.V.., 1257.
https://doi.org/10.1016/j.molstruc.2022.132621

Milović E, Petronijević J, Joksimović N, Beljkaš M, Ružić D, Nikolić K, Vraneš M, Tot A, Đorđić Crnogorac M, Stanojković T, Janković N. Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions. in Journal of Molecular Structure. 2022;1257.
doi:10.1016/j.molstruc.2022.132621 .

Milović, Emilija, Petronijević, Jelena, Joksimović, Nenad, Beljkaš, Milan, Ružić, Dušan, Nikolić, Katarina, Vraneš, Milan, Tot, Aleksandar, Đorđić Crnogorac, Marija, Stanojković, Tatjana, Janković, Nenad, "Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions" in Journal of Molecular Structure, 1257 (2022),
https://doi.org/10.1016/j.molstruc.2022.132621 . .

TY  - JOUR
AU  - Ušjak, Ljuboš
AU  - Milutinović, Violeta
AU  - Đorđić Crnogorac, Marija J.
AU  - Stanojković, Tatjana P.
AU  - Niketić, Marjan S.
AU  - Kukić-Marković, Jelena
AU  - Petrović, Silvana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3957
AB  - Dry MeOH extracts of the twig barks of Pyrus communis subsp. pyraster, P. spinosa and their hybrid P.×jordanovii nothosubsp. velenovskyi, collected in wild in Serbia, were analyzed. By LC/MS, the contents of arbutin (99.9–131.0 mg/g), chlorogenic acid (2.2–6.3 mg/g), catechin (1.0–5.3 mg/g) and total dimeric and trimeric procyanidins (42.2–61.3 mg/g), including procyanidin B2 (8.9–17.2 mg/g), were determined. Colorimetri- cally, high contents of total phenolics (436.2–533.4 mg GAE/g) and tannins (339.4–425.7 mg GAE/g), as well as strong total antioxidant activities (FRAP values 4.5–5.9 mmol Fe2+ /g), and DPPH (SC50 = 6.6–7.1 μg/ml) and hydroxyl radical (SC50 = 447.1–727.7 μg/ml) scavenging abilities were revealed. In vitro, all extracts exhibited notable inhibition of α-amylase (IC50 = 310.8–617.7 μg/ml) and particularly strong inhibition of α-glucosidase (IC50 = 2.1–3.7 μg/ml). Molecular docking predicted that among identified compounds procyanidin B2 is the best inhibitor of these carbohydrate-digesting enzymes. Obtained results showed that the barks of investigated Pyrus hybrid and its parent taxa have similar composition and bioactivity.
PB  - John Wiley and Sons Inc
T2  - Chemistry & Biodiversity
T1  - Barks of Three Wild Pyrus Taxa: Phenolic Constituents, Antioxidant Activity, and in Vitro and in Silico Investigations of α-Amylase and α-Glucosidase Inhibition
VL  - 18
IS  - 10
DO  - 10.1002/cbdv.202100446
ER  - 

@article{
author = "Ušjak, Ljuboš and Milutinović, Violeta and Đorđić Crnogorac, Marija J. and Stanojković, Tatjana P. and Niketić, Marjan S. and Kukić-Marković, Jelena and Petrović, Silvana",
year = "2021",
abstract = "Dry MeOH extracts of the twig barks of Pyrus communis subsp. pyraster, P. spinosa and their hybrid P.×jordanovii nothosubsp. velenovskyi, collected in wild in Serbia, were analyzed. By LC/MS, the contents of arbutin (99.9–131.0 mg/g), chlorogenic acid (2.2–6.3 mg/g), catechin (1.0–5.3 mg/g) and total dimeric and trimeric procyanidins (42.2–61.3 mg/g), including procyanidin B2 (8.9–17.2 mg/g), were determined. Colorimetri- cally, high contents of total phenolics (436.2–533.4 mg GAE/g) and tannins (339.4–425.7 mg GAE/g), as well as strong total antioxidant activities (FRAP values 4.5–5.9 mmol Fe2+ /g), and DPPH (SC50 = 6.6–7.1 μg/ml) and hydroxyl radical (SC50 = 447.1–727.7 μg/ml) scavenging abilities were revealed. In vitro, all extracts exhibited notable inhibition of α-amylase (IC50 = 310.8–617.7 μg/ml) and particularly strong inhibition of α-glucosidase (IC50 = 2.1–3.7 μg/ml). Molecular docking predicted that among identified compounds procyanidin B2 is the best inhibitor of these carbohydrate-digesting enzymes. Obtained results showed that the barks of investigated Pyrus hybrid and its parent taxa have similar composition and bioactivity.",
publisher = "John Wiley and Sons Inc",
journal = "Chemistry & Biodiversity",
title = "Barks of Three Wild Pyrus Taxa: Phenolic Constituents, Antioxidant Activity, and in Vitro and in Silico Investigations of α-Amylase and α-Glucosidase Inhibition",
volume = "18",
number = "10",
doi = "10.1002/cbdv.202100446"
}

Ušjak, L., Milutinović, V., Đorđić Crnogorac, M. J., Stanojković, T. P., Niketić, M. S., Kukić-Marković, J.,& Petrović, S.. (2021). Barks of Three Wild Pyrus Taxa: Phenolic Constituents, Antioxidant Activity, and in Vitro and in Silico Investigations of α-Amylase and α-Glucosidase Inhibition. in Chemistry & Biodiversity
John Wiley and Sons Inc., 18(10).
https://doi.org/10.1002/cbdv.202100446

Ušjak L, Milutinović V, Đorđić Crnogorac MJ, Stanojković TP, Niketić MS, Kukić-Marković J, Petrović S. Barks of Three Wild Pyrus Taxa: Phenolic Constituents, Antioxidant Activity, and in Vitro and in Silico Investigations of α-Amylase and α-Glucosidase Inhibition. in Chemistry & Biodiversity. 2021;18(10).
doi:10.1002/cbdv.202100446 .

Ušjak, Ljuboš, Milutinović, Violeta, Đorđić Crnogorac, Marija J., Stanojković, Tatjana P., Niketić, Marjan S., Kukić-Marković, Jelena, Petrović, Silvana, "Barks of Three Wild Pyrus Taxa: Phenolic Constituents, Antioxidant Activity, and in Vitro and in Silico Investigations of α-Amylase and α-Glucosidase Inhibition" in Chemistry & Biodiversity, 18, no. 10 (2021),
https://doi.org/10.1002/cbdv.202100446 . .

TY  - CONF
AU  - Milutinović, Violeta
AU  - Ušjak, Ljuboš
AU  - Stanojković, Tatjana
AU  - Đorđić Crnogorac, Marija
AU  - Niketić, Marjan
AU  - Petrović, Silvana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5258
AB  - Pyrus × velenovskyi Dostálek (Rosaceae) [P. pyraster (L.) Burgsd. × P. spinosa Forssk.] is a deciduous tree up to 5 m height. Leaf-blades 2.2–4.8 × 1.3–2.7 cm, ± glabrate, ellip tic, gradually narrowed to a rather long petiole. Th is natural hybrid plant was described from Bulgaria, and has been also found in Serbia. The objective of this work was to investigate the phenolic profile, as well as in vitro antioxidant, α-amylase and α-glucosidase inhibitory activities of dried methanol ex tract from the bark of this tree. The plant material was collected in eastern Serbia (Jelašnička Klisura gorge). In the dried bark, the contents of different classes of phenolics were spectrophotometrically determined: total polyphenols (10.36%), tannins (8.78%), procyanidins (4.21%) and phenolic glycosides (3.54%). After pre-extraction with dichloromethane, powdered bark was extracted with methanol by bimaceration at room temperature. In obtained dried methanol extract, using aforementioned spectrophotometric tests, the contents of total polyphenols (33.42%) and tannins (21.55%) were determined, and by HPLC, arbutin, chlorogenic acid, catechin and procyanidin B2 were identifi ed. Its antioxidant activity, i.e. ferric reducing capacity (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH radical scavenging ability, as well as the inhibition of the enzymes α-amylase and α-glucosidase were assessed using corresponding colorimetric assays. Tested dried methanol extract exhibited signifi cant DPPH and OH radical scavenging abilities (SC50 = 6.85 and 12.21 μg/mL, respectively), and ferric reducing capacity (10.74 mmol Fe (II)/g of dried extract), as well as the inhibition of α-amylase (IC50 = 11.4 μg/mL) and α-glucosidase (IC50 = 5.48 μg/mL).
PB  - Institute of Botany and Botanical Garden Jevremovac, Belgrade
C3  - Botanica Serbica, The 7th Balkan Botanical Congress – 7BBC 2018, Book of abstracts
T1  - Phenolic constituents, antioxidant, α-amylase and α-glucosidase inhibitory activities of Pyrus × velenovskyi bark
VL  - 42
IS  - 1 supplement
SP  - 139
EP  - 139
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5258
ER  - 

@conference{
author = "Milutinović, Violeta and Ušjak, Ljuboš and Stanojković, Tatjana and Đorđić Crnogorac, Marija and Niketić, Marjan and Petrović, Silvana",
year = "2018",
abstract = "Pyrus × velenovskyi Dostálek (Rosaceae) [P. pyraster (L.) Burgsd. × P. spinosa Forssk.] is a deciduous tree up to 5 m height. Leaf-blades 2.2–4.8 × 1.3–2.7 cm, ± glabrate, ellip tic, gradually narrowed to a rather long petiole. Th is natural hybrid plant was described from Bulgaria, and has been also found in Serbia. The objective of this work was to investigate the phenolic profile, as well as in vitro antioxidant, α-amylase and α-glucosidase inhibitory activities of dried methanol ex tract from the bark of this tree. The plant material was collected in eastern Serbia (Jelašnička Klisura gorge). In the dried bark, the contents of different classes of phenolics were spectrophotometrically determined: total polyphenols (10.36%), tannins (8.78%), procyanidins (4.21%) and phenolic glycosides (3.54%). After pre-extraction with dichloromethane, powdered bark was extracted with methanol by bimaceration at room temperature. In obtained dried methanol extract, using aforementioned spectrophotometric tests, the contents of total polyphenols (33.42%) and tannins (21.55%) were determined, and by HPLC, arbutin, chlorogenic acid, catechin and procyanidin B2 were identifi ed. Its antioxidant activity, i.e. ferric reducing capacity (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH radical scavenging ability, as well as the inhibition of the enzymes α-amylase and α-glucosidase were assessed using corresponding colorimetric assays. Tested dried methanol extract exhibited signifi cant DPPH and OH radical scavenging abilities (SC50 = 6.85 and 12.21 μg/mL, respectively), and ferric reducing capacity (10.74 mmol Fe (II)/g of dried extract), as well as the inhibition of α-amylase (IC50 = 11.4 μg/mL) and α-glucosidase (IC50 = 5.48 μg/mL).",
publisher = "Institute of Botany and Botanical Garden Jevremovac, Belgrade",
journal = "Botanica Serbica, The 7th Balkan Botanical Congress – 7BBC 2018, Book of abstracts",
title = "Phenolic constituents, antioxidant, α-amylase and α-glucosidase inhibitory activities of Pyrus × velenovskyi bark",
volume = "42",
number = "1 supplement",
pages = "139-139",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5258"
}

Milutinović, V., Ušjak, L., Stanojković, T., Đorđić Crnogorac, M., Niketić, M.,& Petrović, S.. (2018). Phenolic constituents, antioxidant, α-amylase and α-glucosidase inhibitory activities of Pyrus × velenovskyi bark. in Botanica Serbica, The 7th Balkan Botanical Congress – 7BBC 2018, Book of abstracts
Institute of Botany and Botanical Garden Jevremovac, Belgrade., 42(1 supplement), 139-139.
https://hdl.handle.net/21.15107/rcub_farfar_5258

Milutinović V, Ušjak L, Stanojković T, Đorđić Crnogorac M, Niketić M, Petrović S. Phenolic constituents, antioxidant, α-amylase and α-glucosidase inhibitory activities of Pyrus × velenovskyi bark. in Botanica Serbica, The 7th Balkan Botanical Congress – 7BBC 2018, Book of abstracts. 2018;42(1 supplement):139-139.
https://hdl.handle.net/21.15107/rcub_farfar_5258 .

Milutinović, Violeta, Ušjak, Ljuboš, Stanojković, Tatjana, Đorđić Crnogorac, Marija, Niketić, Marjan, Petrović, Silvana, "Phenolic constituents, antioxidant, α-amylase and α-glucosidase inhibitory activities of Pyrus × velenovskyi bark" in Botanica Serbica, The 7th Balkan Botanical Congress – 7BBC 2018, Book of abstracts, 42, no. 1 supplement (2018):139-139,
https://hdl.handle.net/21.15107/rcub_farfar_5258 .