TY  - JOUR
AU  - Elek, Milica
AU  - Đoković, Nemanja
AU  - Frank, Annika
AU  - Oljačić, Slavica
AU  - Živković, Aleksandra
AU  - Nikolić, Katarina
AU  - Stark, Holger
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3793
AB  - Dopamine is an important neurotransmitter in the human brain and its altered concentrations can lead to various neurological diseases. We studied the binding of novel compounds at the dopamine D2 (D2R) and D3 (D3R) receptor subtypes, which belong to the D2-like receptor family. The synthesis, in silico, and in vitro characterization of 10 dopamine receptor ligands were performed. Novel ligands were docked into the D2R and D3R crystal structures to examine the precise binding mode. A quantum mechanics/molecular mechanics study was performed to gain insights into the nature of the intermolecular interactions between the newly introduced pentafluorosulfanyl (SF5) moiety and D2R and D3R. A radioligand displacement assay determined that all of the ligands showed moderate-to-low nanomolar affinities at D2R and D3R, with a slight preference for D3R, which was confirmed in the in silico studies. N-{4-[4-(2-Methoxyphenyl)piperazin-1-yl]butyl}-4-(pentafluoro-λ6-sulfanyl)benzamide (7i) showed the highest D3R affinity and selectivity (pKi values of 7.14 [D2R] and 8.42 [D3R]).
PB  - Wiley-VCH Verlag
T2  - Archiv der Pharmazie
T1  - Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands
DO  - 10.1002/ardp.202000486
ER  - 

@article{
author = "Elek, Milica and Đoković, Nemanja and Frank, Annika and Oljačić, Slavica and Živković, Aleksandra and Nikolić, Katarina and Stark, Holger",
year = "2021",
abstract = "Dopamine is an important neurotransmitter in the human brain and its altered concentrations can lead to various neurological diseases. We studied the binding of novel compounds at the dopamine D2 (D2R) and D3 (D3R) receptor subtypes, which belong to the D2-like receptor family. The synthesis, in silico, and in vitro characterization of 10 dopamine receptor ligands were performed. Novel ligands were docked into the D2R and D3R crystal structures to examine the precise binding mode. A quantum mechanics/molecular mechanics study was performed to gain insights into the nature of the intermolecular interactions between the newly introduced pentafluorosulfanyl (SF5) moiety and D2R and D3R. A radioligand displacement assay determined that all of the ligands showed moderate-to-low nanomolar affinities at D2R and D3R, with a slight preference for D3R, which was confirmed in the in silico studies. N-{4-[4-(2-Methoxyphenyl)piperazin-1-yl]butyl}-4-(pentafluoro-λ6-sulfanyl)benzamide (7i) showed the highest D3R affinity and selectivity (pKi values of 7.14 [D2R] and 8.42 [D3R]).",
publisher = "Wiley-VCH Verlag",
journal = "Archiv der Pharmazie",
title = "Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands",
doi = "10.1002/ardp.202000486"
}

Elek, M., Đoković, N., Frank, A., Oljačić, S., Živković, A., Nikolić, K.,& Stark, H.. (2021). Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands. in Archiv der Pharmazie
Wiley-VCH Verlag..
https://doi.org/10.1002/ardp.202000486

Elek M, Đoković N, Frank A, Oljačić S, Živković A, Nikolić K, Stark H. Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands. in Archiv der Pharmazie. 2021;.
doi:10.1002/ardp.202000486 .

Elek, Milica, Đoković, Nemanja, Frank, Annika, Oljačić, Slavica, Živković, Aleksandra, Nikolić, Katarina, Stark, Holger, "Synthesis, in silico, and in vitro studies of novel dopamine D2 and D3 receptor ligands" in Archiv der Pharmazie (2021),
https://doi.org/10.1002/ardp.202000486 . .

TY  - CONF
AU  - Elek, Milica
AU  - Frank, Annika
AU  - Đoković, Nemanja
AU  - Oljačić, Slavica
AU  - Živković, Aleksandra
AU  - Nikolić, Katarina
AU  - Stark, Holger
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4861
AB  - Dopamine receptors are divided into two subclasses: D1 like receptors (D1 and D5 subtypes) and D2 like
receptors (D2, D3 and D4) [1]. Based on a general pharmacophore [2] we introduced the pentafluorosulfanyl
moiety (SF5-) group as an interesting pharmacological tool to investigate D2 like receptors. This moiety
displays high electronegativity and lipophilicity, while being thermally stable [3] and more resistant to
hydrolysis in comparison to that of other polyfuorinated moieties (e.g. CF3 or OCF3). Four novel compounds
with SF5 substituent have been synthesized, in silico and in vitro tested in order to examine their affinity
and selectivity towards human dopamine D2 and D3 receptor subtypes. All compounds showed high affinity
in the nanomolar concentration ranges at both receptors with ST 2200 expressing highest selectivity. In
silico examination determined high values of coefficient of determination (R2) and Spearman correlation
coefficient revealed good correlation between in silico parameters and experimentally obtained Ki values.
These results show that pentafluorosulfanyl substituent is a highly suitable moiety for structural variations
that has to be further investigated and could serve as novel substituent in numerous compound classes.
PB  - Mu.Ta.Lig COST ACTION CA15135
PB  - Paul Ehrlich Euro-PhD Network
C3  - BOOK of ABSTRACTS MedChem19 Catanzaro
T1  - The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands
SP  - 66
EP  - 66
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4861
ER  - 

@conference{
author = "Elek, Milica and Frank, Annika and Đoković, Nemanja and Oljačić, Slavica and Živković, Aleksandra and Nikolić, Katarina and Stark, Holger",
year = "2019",
abstract = "Dopamine receptors are divided into two subclasses: D1 like receptors (D1 and D5 subtypes) and D2 like
receptors (D2, D3 and D4) [1]. Based on a general pharmacophore [2] we introduced the pentafluorosulfanyl
moiety (SF5-) group as an interesting pharmacological tool to investigate D2 like receptors. This moiety
displays high electronegativity and lipophilicity, while being thermally stable [3] and more resistant to
hydrolysis in comparison to that of other polyfuorinated moieties (e.g. CF3 or OCF3). Four novel compounds
with SF5 substituent have been synthesized, in silico and in vitro tested in order to examine their affinity
and selectivity towards human dopamine D2 and D3 receptor subtypes. All compounds showed high affinity
in the nanomolar concentration ranges at both receptors with ST 2200 expressing highest selectivity. In
silico examination determined high values of coefficient of determination (R2) and Spearman correlation
coefficient revealed good correlation between in silico parameters and experimentally obtained Ki values.
These results show that pentafluorosulfanyl substituent is a highly suitable moiety for structural variations
that has to be further investigated and could serve as novel substituent in numerous compound classes.",
publisher = "Mu.Ta.Lig COST ACTION CA15135, Paul Ehrlich Euro-PhD Network",
journal = "BOOK of ABSTRACTS MedChem19 Catanzaro",
title = "The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands",
pages = "66-66",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4861"
}

Elek, M., Frank, A., Đoković, N., Oljačić, S., Živković, A., Nikolić, K.,& Stark, H.. (2019). The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands. in BOOK of ABSTRACTS MedChem19 Catanzaro
Mu.Ta.Lig COST ACTION CA15135., 66-66.
https://hdl.handle.net/21.15107/rcub_farfar_4861

Elek M, Frank A, Đoković N, Oljačić S, Živković A, Nikolić K, Stark H. The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands. in BOOK of ABSTRACTS MedChem19 Catanzaro. 2019;:66-66.
https://hdl.handle.net/21.15107/rcub_farfar_4861 .

Elek, Milica, Frank, Annika, Đoković, Nemanja, Oljačić, Slavica, Živković, Aleksandra, Nikolić, Katarina, Stark, Holger, "The SF5 moiety as promising substituent for the design of novel D2 and D3 receptors ligands" in BOOK of ABSTRACTS MedChem19 Catanzaro (2019):66-66,
https://hdl.handle.net/21.15107/rcub_farfar_4861 .

TY  - CONF
AU  - Filipić, Slavica
AU  - Elek, Milica
AU  - Popović, Marija
AU  - Ružić, Dušan
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4922
AB  - Fast and simple hydrophilic interactions liquid chromatography method was developed and validated for the analysis of moxonidine and its impurities in pharmaceutical dosage form. The separation was performed on Zorbax RX-SIL column (250 mm x 4.6 mm, 5 µm) using mixture of acetonitrile and 40 mM ammonium-formiat buffer (pH 2.8) in ratio 80:20 (v/v) as mobile phase at flow rate of 1 mL/min, detection at 255 nm and temperature of 25 °C. Under the selected chromatographic conditions separation and analysis of five examined compounds in the mixture is enable within 12 minutes. The validation criteria for selectivity, linearity (r≥0.9976), accuracy  (recovery: 93.66 %-114.08 %), precision (RSD: 0.56%-2.55%) and robustness of the method were fulfilled. The obtained values of the  limit of detection  and quantifiqation revealed that the method can be used for determination of impurities levels below 0.1%.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
T1  - Optimization and validation of a hydrophilic interaction liquid chromatography method for determination of moxonidine and its impurities
VL  - II
SP  - 821
EP  - 824
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4922
ER  - 

@conference{
author = "Filipić, Slavica and Elek, Milica and Popović, Marija and Ružić, Dušan and Nikolić, Katarina and Agbaba, Danica",
year = "2016",
abstract = "Fast and simple hydrophilic interactions liquid chromatography method was developed and validated for the analysis of moxonidine and its impurities in pharmaceutical dosage form. The separation was performed on Zorbax RX-SIL column (250 mm x 4.6 mm, 5 µm) using mixture of acetonitrile and 40 mM ammonium-formiat buffer (pH 2.8) in ratio 80:20 (v/v) as mobile phase at flow rate of 1 mL/min, detection at 255 nm and temperature of 25 °C. Under the selected chromatographic conditions separation and analysis of five examined compounds in the mixture is enable within 12 minutes. The validation criteria for selectivity, linearity (r≥0.9976), accuracy  (recovery: 93.66 %-114.08 %), precision (RSD: 0.56%-2.55%) and robustness of the method were fulfilled. The obtained values of the  limit of detection  and quantifiqation revealed that the method can be used for determination of impurities levels below 0.1%.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia",
title = "Optimization and validation of a hydrophilic interaction liquid chromatography method for determination of moxonidine and its impurities",
volume = "II",
pages = "821-824",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4922"
}

Filipić, S., Elek, M., Popović, M., Ružić, D., Nikolić, K.,& Agbaba, D.. (2016). Optimization and validation of a hydrophilic interaction liquid chromatography method for determination of moxonidine and its impurities. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
Society of Physical Chemists of Serbia., II, 821-824.
https://hdl.handle.net/21.15107/rcub_farfar_4922

Filipić S, Elek M, Popović M, Ružić D, Nikolić K, Agbaba D. Optimization and validation of a hydrophilic interaction liquid chromatography method for determination of moxonidine and its impurities. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia. 2016;II:821-824.
https://hdl.handle.net/21.15107/rcub_farfar_4922 .

Filipić, Slavica, Elek, Milica, Popović, Marija, Ružić, Dušan, Nikolić, Katarina, Agbaba, Danica, "Optimization and validation of a hydrophilic interaction liquid chromatography method for determination of moxonidine and its impurities" in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia, II (2016):821-824,
https://hdl.handle.net/21.15107/rcub_farfar_4922 .

TY  - JOUR
AU  - Filipić, Slavica
AU  - Elek, Milica
AU  - Popović, Marija
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2620
AB  - Fast and simple hydrophilic interaction liquid chromatography (HILIC) method was developed and validated for the analysis of moxonidine and its four impurities (A, B, C, and D) in pharmaceutical dosage form. All experiments were performed on the Agilent Technologies 1200 high-performance liquid chromatography (HPLC) system using Zorbax RX-SIL, 250 mm x 4.6 mm, 5 mu m column as stationary phase (T - 25 degrees C, F - 1 mL/min, and lambda - 255 nm), and mixture of acetonitrile and 40 mM ammonium formate buffer (pH 2.8) 80 : 20 (v/v) as mobile phase. Under the optimal chromatographic conditions, selected by central composite design, separation and analysis of moxonidine and its four impurities are enabled within 12 minutes. Validation of the method was conducted in accordance with ICH guidelines. Based on the obtained results selectivity, linearity (r >= 0.9976), accuracy (recovery: 93.66%-114.08%), precision (RSD: 0.56%-2.55%), and robustness of the method were confirmed. The obtained values of the limit of detection and quantification revealed that the method can be used for determination of impurities levels below 0.1%. Validated method was applied for determination of moxonidine and its impurities in commercially available tablet formulation. Obtained results confirmed that validated method is fast, simple, and reliable for analysis of moxonidine and its impurities in tablets.
PB  - Hindawi Publishing Corp, New York
T2  - Journal of Analytical Methods in Chemistry
T1  - Development of Hydrophilic Interaction Liquid Chromatography Method for the Analysis of Moxonidine and Its Impurities
DO  - 10.1155/2016/3715972
ER  - 

@article{
author = "Filipić, Slavica and Elek, Milica and Popović, Marija and Nikolić, Katarina and Agbaba, Danica",
year = "2016",
abstract = "Fast and simple hydrophilic interaction liquid chromatography (HILIC) method was developed and validated for the analysis of moxonidine and its four impurities (A, B, C, and D) in pharmaceutical dosage form. All experiments were performed on the Agilent Technologies 1200 high-performance liquid chromatography (HPLC) system using Zorbax RX-SIL, 250 mm x 4.6 mm, 5 mu m column as stationary phase (T - 25 degrees C, F - 1 mL/min, and lambda - 255 nm), and mixture of acetonitrile and 40 mM ammonium formate buffer (pH 2.8) 80 : 20 (v/v) as mobile phase. Under the optimal chromatographic conditions, selected by central composite design, separation and analysis of moxonidine and its four impurities are enabled within 12 minutes. Validation of the method was conducted in accordance with ICH guidelines. Based on the obtained results selectivity, linearity (r >= 0.9976), accuracy (recovery: 93.66%-114.08%), precision (RSD: 0.56%-2.55%), and robustness of the method were confirmed. The obtained values of the limit of detection and quantification revealed that the method can be used for determination of impurities levels below 0.1%. Validated method was applied for determination of moxonidine and its impurities in commercially available tablet formulation. Obtained results confirmed that validated method is fast, simple, and reliable for analysis of moxonidine and its impurities in tablets.",
publisher = "Hindawi Publishing Corp, New York",
journal = "Journal of Analytical Methods in Chemistry",
title = "Development of Hydrophilic Interaction Liquid Chromatography Method for the Analysis of Moxonidine and Its Impurities",
doi = "10.1155/2016/3715972"
}

Filipić, S., Elek, M., Popović, M., Nikolić, K.,& Agbaba, D.. (2016). Development of Hydrophilic Interaction Liquid Chromatography Method for the Analysis of Moxonidine and Its Impurities. in Journal of Analytical Methods in Chemistry
Hindawi Publishing Corp, New York..
https://doi.org/10.1155/2016/3715972

Filipić S, Elek M, Popović M, Nikolić K, Agbaba D. Development of Hydrophilic Interaction Liquid Chromatography Method for the Analysis of Moxonidine and Its Impurities. in Journal of Analytical Methods in Chemistry. 2016;.
doi:10.1155/2016/3715972 .

Filipić, Slavica, Elek, Milica, Popović, Marija, Nikolić, Katarina, Agbaba, Danica, "Development of Hydrophilic Interaction Liquid Chromatography Method for the Analysis of Moxonidine and Its Impurities" in Journal of Analytical Methods in Chemistry (2016),
https://doi.org/10.1155/2016/3715972 . .

TY  - JOUR
AU  - Filipić, Slavica
AU  - Elek, Milica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2419
AB  - The quantitative structure-retention relationship (QSRR) study has been performed in order to investigate the retention behavior of 16 guanidine and imidazoline derivatives in the reversed-phase thin-layer chromatography (RP-TLC) system consisting of RP-8 stationary phase and the mixture of methanol, water, and ammonia as the mobile phase. Statistical results obtained in the one-parameter model with KOWWINlog P indicated that the lipophilicity of the investigated compounds could be determined based on the respective retentions. Three different modeling methodologies such as stepwise multiple linear regression (MLR), partial least squares regression (PLS), and artificial neural networks (ANN) were used in the QSRR approach and for the selection of the most important variables that describe the behavior of the investigated compounds the best. The performance of the developed stepwise MLR-QSRR, PLS-QSRR, and ANN-QSRR models was tested by cross-validation and the external test set prediction. The validated models were compared, and the optimal QSRR model (stepwise MLR-QSRR) was selected. Besides lipophilicity (KOWWINlog P), the number of secondary (aliphatic) amines (nRNHR) among the tested compounds has the strongest influence on the retention in the examined RP-TLC system. The predictive performance of the selected QSRR model suggests its applicability for a reliable prediction of the retention behavior for the congeners.
PB  - Akademiai Kiado Zrt, Budapest
T2  - Journal of Planar Chromatography - Modern TLC
T1  - Quantitative Structure-Retention Relationship Modeling of the Retention Behavior of Guanidine and Imidazoline Derivatives in Reversed-Phase Thin-Layer Chromatography
VL  - 28
IS  - 2
SP  - 119
EP  - 125
DO  - 10.1556/JPC.28.2015.2.6
ER  - 

@article{
author = "Filipić, Slavica and Elek, Milica and Nikolić, Katarina and Agbaba, Danica",
year = "2015",
abstract = "The quantitative structure-retention relationship (QSRR) study has been performed in order to investigate the retention behavior of 16 guanidine and imidazoline derivatives in the reversed-phase thin-layer chromatography (RP-TLC) system consisting of RP-8 stationary phase and the mixture of methanol, water, and ammonia as the mobile phase. Statistical results obtained in the one-parameter model with KOWWINlog P indicated that the lipophilicity of the investigated compounds could be determined based on the respective retentions. Three different modeling methodologies such as stepwise multiple linear regression (MLR), partial least squares regression (PLS), and artificial neural networks (ANN) were used in the QSRR approach and for the selection of the most important variables that describe the behavior of the investigated compounds the best. The performance of the developed stepwise MLR-QSRR, PLS-QSRR, and ANN-QSRR models was tested by cross-validation and the external test set prediction. The validated models were compared, and the optimal QSRR model (stepwise MLR-QSRR) was selected. Besides lipophilicity (KOWWINlog P), the number of secondary (aliphatic) amines (nRNHR) among the tested compounds has the strongest influence on the retention in the examined RP-TLC system. The predictive performance of the selected QSRR model suggests its applicability for a reliable prediction of the retention behavior for the congeners.",
publisher = "Akademiai Kiado Zrt, Budapest",
journal = "Journal of Planar Chromatography - Modern TLC",
title = "Quantitative Structure-Retention Relationship Modeling of the Retention Behavior of Guanidine and Imidazoline Derivatives in Reversed-Phase Thin-Layer Chromatography",
volume = "28",
number = "2",
pages = "119-125",
doi = "10.1556/JPC.28.2015.2.6"
}

Filipić, S., Elek, M., Nikolić, K.,& Agbaba, D.. (2015). Quantitative Structure-Retention Relationship Modeling of the Retention Behavior of Guanidine and Imidazoline Derivatives in Reversed-Phase Thin-Layer Chromatography. in Journal of Planar Chromatography - Modern TLC
Akademiai Kiado Zrt, Budapest., 28(2), 119-125.
https://doi.org/10.1556/JPC.28.2015.2.6

Filipić S, Elek M, Nikolić K, Agbaba D. Quantitative Structure-Retention Relationship Modeling of the Retention Behavior of Guanidine and Imidazoline Derivatives in Reversed-Phase Thin-Layer Chromatography. in Journal of Planar Chromatography - Modern TLC. 2015;28(2):119-125.
doi:10.1556/JPC.28.2015.2.6 .

Filipić, Slavica, Elek, Milica, Nikolić, Katarina, Agbaba, Danica, "Quantitative Structure-Retention Relationship Modeling of the Retention Behavior of Guanidine and Imidazoline Derivatives in Reversed-Phase Thin-Layer Chromatography" in Journal of Planar Chromatography - Modern TLC, 28, no. 2 (2015):119-125,
https://doi.org/10.1556/JPC.28.2015.2.6 . .