Details

Autor(en) / Beteiligte

• da Silva, Daniel Schuch
• Soares, Mayara Sandrielly Pereira
• Martini, Franciele
• Pesarico, Ana Paula
• de Mattos, Bruna da Silveira
• de Souza, Anita Avila
• da Silva, Cesar Emiliano Hoffman
• Scaini, João Luis Rheingantz
• Machado, Karina dos Santos
• Wayne Nogueira, Cristina
• Spanevello, Roselia Maria
• Cunico, Wilson

Titel

In Vitro Effects of 2-{4-[Methylthio(methylsulfonyl)]phenyl}-3-substitutedthiazolidin-4-ones on the Acetylcholinesterase Activity in Rat Brain and Lymphocytes: Isoform Selectivity, Kinetic Analysis, and Molecular Docking

Ist Teil von

• Neurochemical research, 2020-02, Vol.45 (2), p.241-253

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2020

Quelle

SpringerNature Journals

Beschreibungen/Notizen

• This work evaluated the in vitro effect of thiazolidin-4-ones on the activity of AChE (total and isoforms) isolated from the cerebral cortex, hippocampus, and lymphocytes. Kinetic parameters were evaluated and molecular docking was performed. Our results showed that thiazolidinones derived from 4-(methylthio)benzaldehyde ( 1 ) and from 4-(methylsulfonyl)benzaldehyde ( 2 ) were capable of inhibiting the AChE activity in vitro. Three compounds, two with a propylpiperidine ( 1b and 2b ) moiety and one with a 3-(diethylamino)propyl ( 1c ) moiety showed IC 50 values of 13.81 μM, and 3.13 μM ( 1b ), 55.36 μM and 44.33 μM ( 1c ) for cerebral cortex and hippocampus, respectively, and 3.11 μM for both ( 2b ). Enzyme kinetics revealed that the type of AChE inhibition was mixed. Compound 1b inhibited the G1 and G4 AChE isoforms, while compounds 1c and 2b selectively inhibited the G4 isoform. Molecular docking showed a possible three-dimensional fit into the enzyme. Our findings showed that these thiazolidin-4-ones, especially those containing the propylpiperidine core, have a potential cholinesterase inhibitory activity and can be considered good candidates for future Alzheimer’s therapy.