DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF HYBRID MOLECULES FOR THE MULTITARGETED TREATMENT OF ALZHEIMER

ABTRACT

Alzheimer's disease, first described by Alois Alzheimer at the beginning of the 20th century, is a neuropathology whose frequency increases with age. This multifactorial disease is characterized by the presence of lesions in the central nervous system: extracellular amyloid plaques due to deposition of β-amyloid peptides and degeneration of neurons due to aggregation of neurofibrillar Tau proteins. Given the multifactorial nature of the disease, a new approach to treatments is to simultaneously target multiple factors with one or more molecules administered simultaneously. The proposed project is part of this approach aiming at the design, synthesis and biological evaluation of indolysin-derived hybrid compounds. These indolizins are physically interesting molecules because of their fluorescence as well as because they possess a wide range of biological and therapeutic properties, including proven antioxidant and acetylcholinesterase inhibitory activities, interesting activities in anti-Alzheimer's strategies. The project aims to develop this family of compounds to optimize acetylcholinesterase inhibitory activity, and to target other markers of the disease (amyloid plaques, neurofibrillary degeneration).