QuinoxalineTacrine QT78, a Cholinesterase Inhibitor as a Potential Ligand for Alzheimer’s Disease Therapy

oleh: Eva Ramos, Alejandra Palomino-Antolín, Manuela Bartolini, Isabel Iriepa, Ignacio Moraleda, Daniel Diez-Iriepa, Abdelouahid Samadi, Carol V. Cortina, Mourad Chioua, Javier Egea, Alejandro Romero, José Marco-Contelles

Format: Article
Diterbitkan: MDPI AG 2019-04-01

Deskripsi

We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid <b>QT78</b> in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer&#8217;s disease therapy. We have found that <b>QT78</b> is less toxic than tacrine at high concentrations (from 100 &#956;M to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC<sub>50</sub> (hAChE) = 22.0 &#177; 1.3 &#956;M; IC<sub>50</sub> (hBuChE) = 6.79 &#177; 0.33 &#956;M). Moreover, <b>QT78</b> showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer&#8217;s disease.