In Silico and In Vivo Evaluation of a New Derivative from Memantine and Sinapic Acid (N-Sinapoyl-Memantine) as Candidate for the Management of Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease which has rather complex pathophysiology. During its course several neurotransmitter neuronal systems get affected as acetylcholinergic, glutamatergic, gamma-aminobutyric acid (GABA)ergic system and etc. Such complex physiology requires sophisticated approach of pharmaceutical management. Therefore, multi-target drugs seem to be an appealing solution. In the present study we designed and synthesized a hybrid molecule - N-sinapoylamide of memantine, whose parent molecules memantine (MEM) and sinapic acid has been shown in vivo to impact glutamatergic and acetylcholinergic and GABA-ergic systems respectively. In silico comparative testing of these molecules was performed and their patterns of interaction with the target enzymes or molecular complexes were analyzed and some of the mechanisms of action were proposed. Consequently, in vivo testing was performed on scopolamine mice model of AD and the results overly confirm part of the in silico findings. Therefore the hybrid molecule (N-Sinapoyl-memantine) seems to be a potent candidate for further evaluation in the management of AD.