Principal Investigators


Mgr. Martin Horák, Ph.D.

Institution


Institute of Physiology of the AS CR, v.v.i.

Contact information of lead PI


Country


Czech Republic

Title of project or programme


Novel hybrid compounds in the cognitive decline caused by neurodegeneration

Source of funding information


Czech Science Foundation

Total sum awarded (Euro)


€ 369,259

Start date of award


01/01/2016

Total duration of award in years


3

Keywords


Research Abstract


This project follow-up with ending 5-year project focused on hybrid compounds. Based on preliminary data, we would like to deeply investigate newly designed hybrids combining AChEI pharmacophore and NMDA antagonist pharmacophore in a single molecule. We hypothesize that simultaneous inhibition of AChE and NMDA receptors results in amelioration of the cognitive decline associated with neurodegeneration. Using in vitro pharmacological/toxicological profile screening of newly prepared compounds and deep characterization of NMDA and AChE interaction, one candidate will be selected. Subacute toxicity, bioavailability and dosing scheme for animal model will be assessed. Subsequently, the compound will undergo in vivo behavioral validation of pro-cognitive properties with subsequent ex vivo biochemical assessment of underlying mechanisms of action. Altogether, the pro-cognitive therapeutic value of such hybrid compounds will be determined.

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