Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer’s disease

Multi-Target-Directed Ligands and Alzheimer’s Disease Carlo Melchiorre Dipartimento di Scienze Farmaceutiche, Alma Mater Studiorum – Università di Bologna Via Belmeloro 6, 40126 Bologna, Italy, carlo.melchiorre@unibo.it Alzheimer’s disease (AD) is a complex neurological affection, characterized by loss of memory and progressive deficits in different cognitive domains and by massive deposits of aggregated proteins that form intracellular tangles and extra-cellular senile plaques. AD still represents a formidable challenge to medicinal chemists because, despite the large amount of basic research carried out into the causes of the disease, progress towards effective pharmacological treatments has been remarkably slow. The multi-factorial nature of AD forms the basis for the growing consensus that the winning approach for the future treatment of the disease will be therapy with drug cocktails or multi-functional drugs. Clearly, multi-functional drugs would obviate the challenge of administering a combination of drugs with potentially different ADME properties and would also simplify the therapeutic regimen for individuals who may have difficulty with compliance. Consequently, efforts to discover anti-Alzheimer drugs should be devoted to the design of new compounds that are able to hit different selected targets. Following this rationale, new multi-target-directed ligands against AD have been discovered. That is, single molecules that can simultaneously exhibit multiple pharmacological properties, such as cholinergic transmission enhancement and inhibition of both Ab accumulation and oxidative stress, leading to a synergic effect. The results of this approach will be illustrated.