Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding
Authors
Jevtić, Ivana
Lai, Thu Hang

Penjišević, Jelena

Dukić-Stefanović, Sladjana
Andrić, Deana

Brust, Peter

Kostić Rajačić, Slađana

Teodoro, Rodrigo

Article (Published version)
Metadata
Show full item recordAbstract
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.
Keywords:
MAO-B / positron emission tomography / piperazine / cinnamic acidSource:
Molecules, 2020, 25, 21, 4941-Publisher:
- MDPI
Funding / projects:
- Ministry of Education, Science and Technological Development of the Republic of Serbia (grant No. 451-03-01732/2017-09/4) and the Deutscher Akademischer Austauschdienst (DAAD, grant No. 57391403) within the Bilateral project “Development of new fluorinated radioligands for PET imaging of monoamine oxidase B (MAO-B)”
DOI: 10.3390/molecules25214941
ISSN: 1420-3049
WoS: 000589372800001
Scopus: 2-s2.0-85094821384
Collections
Institution/Community
IHTMTY - JOUR AU - Jevtić, Ivana AU - Lai, Thu Hang AU - Penjišević, Jelena AU - Dukić-Stefanović, Sladjana AU - Andrić, Deana AU - Brust, Peter AU - Kostić Rajačić, Slađana AU - Teodoro, Rodrigo PY - 2020 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/4040 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 and Lai, Thu Hang and Penjišević, Jelena and Dukić-Stefanović, Sladjana 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., 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 I, 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, Lai, Thu Hang, Penjišević, Jelena, Dukić-Stefanović, Sladjana, 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 . .