TY  - JOUR
AU  - Dukić-Stefanović, Slađana
AU  - Hang Lai, Thu
AU  - Toussaint, Magali
AU  - Clauß, Oliver
AU  - Jevtić, Ivana I.
AU  - Penjišević, Jelena
AU  - Andrić, Deana
AU  - Ludwig, Friedrich-Alexander
AU  - Gündel, Daniel
AU  - Deuther-Conrad, Winnie
AU  - Kostić-Rajačić, Slađana
AU  - Brust, Peter
AU  - Teodoro, Rodrigo
PY  - 2021
UR  - https://www.sciencedirect.com/science/article/pii/S0960894X21004819
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4591
AB  - Monoamine oxidases (MAOs) play a key role in the metabolism of major monoamine neurotransmitters. In particular, the upregulation of MAO-B in Parkinson’s disease, Alzheimer’s disease and cancer augmented the development of selective MAO-B inhibitors for diagnostic and therapeutic purposes, such as the anti-parkinsonian MAO-B irreversible binder l-deprenyl (Selegiline®). Herein we report on the synthesis of novel fluorinated indanone derivatives for PET imaging of MAO-B in the brain. Out of our series, the derivatives 6, 8, 9 and 13 are amongst the most affine and selective ligands for MAO-B reported so far. For the derivative 6-((3-fluorobenzyl)oxy)-2,3-dihydro-1H-inden-1-one (6) exhibiting an outstanding affinity (Ki MAO-B = 6 nM), an automated copper-mediated radiofluorination starting from the pinacol boronic ester 17 is described. An in vitro screening in different species revealed a MAO-B region-specific accumulation of [18F]6 in rats and piglets in comparison to L-[3H]deprenyl. The pre-clinical in vivo assessment of [18F]6 in mice demonstrated the potential of indanones to readily cross the blood–brain barrier. Nonetheless, parallel in vivo metabolism studies indicated the presence of blood–brain barrier metabolites, thus arguing for further structural modifications. With the matching analytical profiles of the radiometabolite analysis from the in vitro liver microsome studies and the in vivo evaluation, the structure’s elucidation of the blood–brain barrier penetrant radiometabolites is possible and will serve as basis for the development of new indanone derivatives suitable for the PET imaging of MAO-B.
PB  - Elsevier
T2  - Bioorganic & Medicinal Chemistry Letters
T1  - In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain
VL  - 48
SP  - 128254
DO  - 10.1016/j.bmcl.2021.128254
ER  - 

@article{
author = "Dukić-Stefanović, Slađana and Hang Lai, Thu and Toussaint, Magali and Clauß, Oliver and Jevtić, Ivana I. and Penjišević, Jelena and Andrić, Deana and Ludwig, Friedrich-Alexander and Gündel, Daniel and Deuther-Conrad, Winnie and Kostić-Rajačić, Slađana and Brust, Peter and Teodoro, Rodrigo",
year = "2021",
abstract = "Monoamine oxidases (MAOs) play a key role in the metabolism of major monoamine neurotransmitters. In particular, the upregulation of MAO-B in Parkinson’s disease, Alzheimer’s disease and cancer augmented the development of selective MAO-B inhibitors for diagnostic and therapeutic purposes, such as the anti-parkinsonian MAO-B irreversible binder l-deprenyl (Selegiline®). Herein we report on the synthesis of novel fluorinated indanone derivatives for PET imaging of MAO-B in the brain. Out of our series, the derivatives 6, 8, 9 and 13 are amongst the most affine and selective ligands for MAO-B reported so far. For the derivative 6-((3-fluorobenzyl)oxy)-2,3-dihydro-1H-inden-1-one (6) exhibiting an outstanding affinity (Ki MAO-B = 6 nM), an automated copper-mediated radiofluorination starting from the pinacol boronic ester 17 is described. An in vitro screening in different species revealed a MAO-B region-specific accumulation of [18F]6 in rats and piglets in comparison to L-[3H]deprenyl. The pre-clinical in vivo assessment of [18F]6 in mice demonstrated the potential of indanones to readily cross the blood–brain barrier. Nonetheless, parallel in vivo metabolism studies indicated the presence of blood–brain barrier metabolites, thus arguing for further structural modifications. With the matching analytical profiles of the radiometabolite analysis from the in vitro liver microsome studies and the in vivo evaluation, the structure’s elucidation of the blood–brain barrier penetrant radiometabolites is possible and will serve as basis for the development of new indanone derivatives suitable for the PET imaging of MAO-B.",
publisher = "Elsevier",
journal = "Bioorganic & Medicinal Chemistry Letters",
title = "In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain",
volume = "48",
pages = "128254",
doi = "10.1016/j.bmcl.2021.128254"
}

Dukić-Stefanović, S., Hang Lai, T., Toussaint, M., Clauß, O., Jevtić, I. I., Penjišević, J., Andrić, D., Ludwig, F., Gündel, D., Deuther-Conrad, W., Kostić-Rajačić, S., Brust, P.,& Teodoro, R.. (2021). In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain. in Bioorganic & Medicinal Chemistry Letters
Elsevier., 48, 128254.
https://doi.org/10.1016/j.bmcl.2021.128254

Dukić-Stefanović S, Hang Lai T, Toussaint M, Clauß O, Jevtić II, Penjišević J, Andrić D, Ludwig F, Gündel D, Deuther-Conrad W, Kostić-Rajačić S, Brust P, Teodoro R. In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain. in Bioorganic & Medicinal Chemistry Letters. 2021;48:128254.
doi:10.1016/j.bmcl.2021.128254 .

Dukić-Stefanović, Slađana, Hang Lai, Thu, Toussaint, Magali, Clauß, Oliver, Jevtić, Ivana I., Penjišević, Jelena, Andrić, Deana, Ludwig, Friedrich-Alexander, Gündel, Daniel, Deuther-Conrad, Winnie, Kostić-Rajačić, Slađana, Brust, Peter, Teodoro, Rodrigo, "In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain" in Bioorganic & Medicinal Chemistry Letters, 48 (2021):128254,
https://doi.org/10.1016/j.bmcl.2021.128254 . .

TY  - DATA
AU  - Dukić-Stefanović, Slađana
AU  - Hang Lai, Thu
AU  - Toussaint, Magali
AU  - Clauß, Oliver
AU  - Jevtić, Ivana I.
AU  - Penjišević, Jelena
AU  - Andrić, Deana
AU  - Ludwig, Friedrich-Alexander
AU  - Gündel, Daniel
AU  - Deuther-Conrad, Winnie
AU  - Kostić-Rajačić, Slađana
AU  - Brust, Peter
AU  - Teodoro, Rodrigo
PY  - 2021
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4592
PB  - Elsevier
T2  - Bioorganic & Medicinal Chemistry Letters
T1  - Supplementary data for the article: Dukić-Stefanović, S.; Hang Lai, T.; Toussaint, M.; Clauß, O.; Jevtić, I. I.; Penjišević, J. Z.; Andrić, D.; Ludwig, F.-A.; Gündel, D.; Deuther-Conrad, W.; Kostić-Rajačić, S. V.; Brust, P.; Teodoro, R. In Vitro and in Vivo Evaluation of Fluorinated Indanone Derivatives as Potential Positron Emission Tomography Agents for the Imaging of Monoamine Oxidase B in the Brain. Bioorganic & Medicinal Chemistry Letters 2021, 48, 128254. https://doi.org/10.1016/j.bmcl.2021.128254.
UR  - https://hdl.handle.net/21.15107/rcub_cherry_4592
ER  - 

@misc{
author = "Dukić-Stefanović, Slađana and Hang Lai, Thu and Toussaint, Magali and Clauß, Oliver and Jevtić, Ivana I. and Penjišević, Jelena and Andrić, Deana and Ludwig, Friedrich-Alexander and Gündel, Daniel and Deuther-Conrad, Winnie and Kostić-Rajačić, Slađana and Brust, Peter and Teodoro, Rodrigo",
year = "2021",
publisher = "Elsevier",
journal = "Bioorganic & Medicinal Chemistry Letters",
title = "Supplementary data for the article: Dukić-Stefanović, S.; Hang Lai, T.; Toussaint, M.; Clauß, O.; Jevtić, I. I.; Penjišević, J. Z.; Andrić, D.; Ludwig, F.-A.; Gündel, D.; Deuther-Conrad, W.; Kostić-Rajačić, S. V.; Brust, P.; Teodoro, R. In Vitro and in Vivo Evaluation of Fluorinated Indanone Derivatives as Potential Positron Emission Tomography Agents for the Imaging of Monoamine Oxidase B in the Brain. Bioorganic & Medicinal Chemistry Letters 2021, 48, 128254. https://doi.org/10.1016/j.bmcl.2021.128254.",
url = "https://hdl.handle.net/21.15107/rcub_cherry_4592"
}

Dukić-Stefanović, S., Hang Lai, T., Toussaint, M., Clauß, O., Jevtić, I. I., Penjišević, J., Andrić, D., Ludwig, F., Gündel, D., Deuther-Conrad, W., Kostić-Rajačić, S., Brust, P.,& Teodoro, R.. (2021). Supplementary data for the article: Dukić-Stefanović, S.; Hang Lai, T.; Toussaint, M.; Clauß, O.; Jevtić, I. I.; Penjišević, J. Z.; Andrić, D.; Ludwig, F.-A.; Gündel, D.; Deuther-Conrad, W.; Kostić-Rajačić, S. V.; Brust, P.; Teodoro, R. In Vitro and in Vivo Evaluation of Fluorinated Indanone Derivatives as Potential Positron Emission Tomography Agents for the Imaging of Monoamine Oxidase B in the Brain. Bioorganic & Medicinal Chemistry Letters 2021, 48, 128254. https://doi.org/10.1016/j.bmcl.2021.128254.. in Bioorganic & Medicinal Chemistry Letters
Elsevier..
https://hdl.handle.net/21.15107/rcub_cherry_4592

Dukić-Stefanović S, Hang Lai T, Toussaint M, Clauß O, Jevtić II, Penjišević J, Andrić D, Ludwig F, Gündel D, Deuther-Conrad W, Kostić-Rajačić S, Brust P, Teodoro R. Supplementary data for the article: Dukić-Stefanović, S.; Hang Lai, T.; Toussaint, M.; Clauß, O.; Jevtić, I. I.; Penjišević, J. Z.; Andrić, D.; Ludwig, F.-A.; Gündel, D.; Deuther-Conrad, W.; Kostić-Rajačić, S. V.; Brust, P.; Teodoro, R. In Vitro and in Vivo Evaluation of Fluorinated Indanone Derivatives as Potential Positron Emission Tomography Agents for the Imaging of Monoamine Oxidase B in the Brain. Bioorganic & Medicinal Chemistry Letters 2021, 48, 128254. https://doi.org/10.1016/j.bmcl.2021.128254.. in Bioorganic & Medicinal Chemistry Letters. 2021;.
https://hdl.handle.net/21.15107/rcub_cherry_4592 .

Dukić-Stefanović, Slađana, Hang Lai, Thu, Toussaint, Magali, Clauß, Oliver, Jevtić, Ivana I., Penjišević, Jelena, Andrić, Deana, Ludwig, Friedrich-Alexander, Gündel, Daniel, Deuther-Conrad, Winnie, Kostić-Rajačić, Slađana, Brust, Peter, Teodoro, Rodrigo, "Supplementary data for the article: Dukić-Stefanović, S.; Hang Lai, T.; Toussaint, M.; Clauß, O.; Jevtić, I. I.; Penjišević, J. Z.; Andrić, D.; Ludwig, F.-A.; Gündel, D.; Deuther-Conrad, W.; Kostić-Rajačić, S. V.; Brust, P.; Teodoro, R. In Vitro and in Vivo Evaluation of Fluorinated Indanone Derivatives as Potential Positron Emission Tomography Agents for the Imaging of Monoamine Oxidase B in the Brain. Bioorganic & Medicinal Chemistry Letters 2021, 48, 128254. https://doi.org/10.1016/j.bmcl.2021.128254." in Bioorganic & Medicinal Chemistry Letters (2021),
https://hdl.handle.net/21.15107/rcub_cherry_4592 .

TY  - JOUR
AU  - Jevtić, Ivana I.
AU  - Lai, Thu Hang
AU  - Penjišević, Jelena
AU  - Dukić-Stefanović, Slađana
AU  - Andrić, Deana
AU  - Brust, Peter
AU  - Kostić-Rajačić, Slađana
AU  - Teodoro, Rodrigo
PY  - 2020
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4272
AB  - Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.
PB  - MDPI
T2  - Molecules
T1  - Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding
VL  - 25
IS  - 21
SP  - 4941
DO  - 10.3390/molecules25214941
ER  - 

@article{
author = "Jevtić, Ivana I. and Lai, Thu Hang and Penjišević, Jelena and Dukić-Stefanović, Slađana and Andrić, Deana and Brust, Peter and Kostić-Rajačić, Slađana and Teodoro, Rodrigo",
year = "2020",
abstract = "Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.",
publisher = "MDPI",
journal = "Molecules",
title = "Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding",
volume = "25",
number = "21",
pages = "4941",
doi = "10.3390/molecules25214941"
}

Jevtić, I. I., Lai, T. H., Penjišević, J., Dukić-Stefanović, S., Andrić, D., Brust, P., Kostić-Rajačić, S.,& Teodoro, R.. (2020). Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding. in Molecules
MDPI., 25(21), 4941.
https://doi.org/10.3390/molecules25214941

Jevtić II, Lai TH, Penjišević J, Dukić-Stefanović S, Andrić D, Brust P, Kostić-Rajačić S, Teodoro R. Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding. in Molecules. 2020;25(21):4941.
doi:10.3390/molecules25214941 .

Jevtić, Ivana I., Lai, Thu Hang, Penjišević, Jelena, Dukić-Stefanović, Slađana, Andrić, Deana, Brust, Peter, Kostić-Rajačić, Slađana, Teodoro, Rodrigo, "Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding" in Molecules, 25, no. 21 (2020):4941,
https://doi.org/10.3390/molecules25214941 . .