Development of a New Palmitate-Derived Hydrazone as a Potential Metallophore for the Management of Alzheimer's Disease

Alzheimer's disease is characterized by the extracellular deposition of fibrillar plaques of amyloid-β peptide (Aβ). Metal ions, such as copper(II), are capable of binding to the Aβ peptide with high affinity, forming Aβ-copper complexes that accentuate oligomerization and fibrillation, increasing membrane permeability and causing oxidative stress. Additionally, extensive damage to the integrity of neuronal membranes has been reported, showing the pathological complexity of this pathology. Based on this, our group has been working with a class of polydentate ligands called N-acylhydrazones, capable of competing with the peptide for the binding of copper and, in this case, interacting with biomembranes. The present work describes synthesis and characterization of a new N-acylhydrazone named X1-PMT, derived from palmitohydrazide. This compound has a hydrophobic tail containing 16 carbons, whose purpose is related to potential interaction with biological membranes and, being a N-acylhydrazone, it also has the capacity to chelate metals.