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Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding

Authors :
Ivana I. Jevtić
Thu Hang Lai
Jelena Z. Penjišević
Sladjana Dukić-Stefanović
Deana B. Andrić
Peter Brust
Sladjana V. Kostić-Rajačić
Rodrigo Teodoro
Source :
Molecules, Vol 25, Iss 21, p 4941 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 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.

Details

Language :
English
ISSN :
14203049
Volume :
25
Issue :
21
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.29f34f7b5de46af9ce9104eb53eab9a
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules25214941