Natural scaffolds with potential metal chelating activity for the multi-target therapy of Alzheimer´s Disease: a preliminary study

According to the theory of the multifactorial origin of Alzheimer's Disease (AD), in recent years many scientists focused their studies on multi-target agents, acting on features such as the inhibition of acetylcholinesterase (AChE), monoamine oxidases (MAOs) or ?-amyloid (A?) aggregation, the N-methyl-D-aspartate (NMDA) receptor antagonism, and the antioxidant activity, which have been recognized as important at the onset of the pathology [1, 2]. However, recent evidence has shown that the removal and/or redistribution of metal ions at the level of the nervous system can significantly reduce the formation of A? and thus of reactive oxygen species, which are typical of AD and other neurodegenerative diseases. Therefore, the chelation of copper and/or zinc cations is a new fascinating, attractive target for innovative therapies [3]. Five secondary metabolites of plants or fungi (1 tenuazonic acid, 2 mycophenolic acid, 3 2-epiradicinol, 4 radicinin, 5 6-methoxymellein) with suitable structural characteristics have been selected and assayed in order to preliminary evaluate their metal chelating properties (Figure 1). These molecules have been also tested on other targets, considering that many natural compounds are able to inhibit the A? aggregation as well as possess an anti-oxidant and anticholinesterase activity [4]. In this Communication we will present the promising results obtained with some selected hit compounds which will address our future studies of Structure-Activity Relationships.