New Tacrine derivatives and Tacrine-Chitosan systems for application against degenerative diseases

Chitosan is a natural non-toxic, biodegradable and biocompatible biopolymer, which is derived from chitin, whose structure allows a wide variety of chemical modifications that can confer new physical-chemical properties, functions and applications in different fields.

Among the great challenges facing the Society is the search for solutions to Alzheimer's disease. This disease presents high cellular oxidative stress, as a result of the imbalance between the oxidizing species generated in the cells and antioxidant compounds. One of the strategies used in the treatment of Alzheimer's is based on the use of acetylcholinesterase (AChE) inhibitors, an enzyme that catalyzes the hydrolysis of acetylcholine, a neurotransmitter involved in memory. In this context, Tacrine was the first drug approved for this purpose, later withdrawn due to liver damage caused by inducing oxidative stress.

Therefore, in the present work, new Tacrine derivatives that could reduce the original hepatotoxicity of the compound while preserving its properties as an AChE inhibitor have been prepared and characterized. Furthermore, by means of the formation of different functional bridges between Tacrine and Chitosan, new hybrid systems Tacrina-Chitosan, have been synthesized and characterized in order to serve as vectors of the drug in the human body. Among them, presence of a selenourea bridge must contribute to reduce oxidative stress, given the property of Se to reduce the number of ROS species in the cell.