Tacrine-Natural-Product Hybrids for Alzheimer's Disease Therapy.

Alzheimer's disease (AD) is a complex, neurodegenerative pathology showing, among others, high cholinergic and neurotransmitter deficits, oxidative stress, inflammation, A-aggregation resulting in senile plaques formation, and hyperphosphorylation of tau-protein leading to neurofibrillary tangles. Due to its multifactorial and complex nature, multitarget directed small-molecules able to simultaneously inhibit or bind diverse biological targets involved in the progress and development of AD are considered now the best therapeutic strategy to design new compounds for AD therapy. Among them, tacrine is a very well known standard-gold ligand, and natural products have been a traditional source of new agents for diverse therapeutic treatments. In this review we will update recent developments of multitarget tacrine-natural products hybrids for AD therapy.