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Potential multitarget agents for the treatment of neurodegenerations: dual H3R/AChE inhibitors with associated chelating properties

Grant number: 21/03387-0
Support type:Scholarships in Brazil - Master
Effective date (Start): December 01, 2021
Effective date (End): June 30, 2023
Field of knowledge:Health Sciences - Pharmacy
Principal researcher:João Paulo dos Santos Fernandes
Grantee:Flávia Barrio Lopes
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

The interest in multi-target drugs, i.e., molecules capable of interacting in more than one target simultaneously, has been growing in recent years as a new way to treat complex diseases, which involve different signaling pathways, connected to each other. This is the case for neurodegenerative diseases (for example, Alzheimer's disease), which involve changes in cognition-related pathways due to reduced neurotransmission caused by neuronal death. As the processes that lead to learning and memory formation are related to the activation of cholinergic and histaminergic pathways, the modulation of targets in these pathways can represent a significant advance in the treatment of diseases that affect cognitive processes, especially allied to the antioxidant activity of chelating agents. In this regard, this project aims to synthesize and evaluate the potential of compounds such as anticholinesterase agents, histamine H3 antagonists and metal chelators, designed by overlapping structural requirements for the interaction with these selected targets. The evaluation of relative selectivity towards butyrylcholinesterase and other histamine receptors will also be carried out. The compounds will be prepared using synthetic methodologies well established in the group, which generally lead to good yields. In the end, it is expected that agents with activity on the selected targets will be identified and that they will be able to bring information about the relationships between structure and activity that allow to plan new superior compounds. (AU)

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