β-Cyclodextrin Inclusion Complex of a New Isoxazole‑Based N‑acylhydrazone is still Capable of Complexing Cu2+ Ions: Potential for Alzheimer’s Treatment

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Abstract

Alzheimer’s disease is the most prevalent form of dementia, characterized by β-amyloid aggregation, neuroinflammation, oxidative stress, and neurotransmitter imbalance. Since monoamine oxidase (MAO) contributes to oxidative metabolism, it represents an important therapeutic target. In this study, a novel phenylisoxazole-based N-acylhydrazone ligand (X1FIX) was synthesized and showed non-selective MAO inhibition, with 29.9% inhibition of MAO-A and 27.4% of MAO-B at 100 μM. To improve its solubility and bioavailability, X1FIX was complexed with β-cyclodextrin. The inclusion complex also formed a Cu(II) complex, suggesting the ability to compete with β-amyloid for copper binding, potentially reducing oxidative stress. These findings highlight X1FIX as a promising multitarget candidate for Alzheimer’s disease treatment.

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Institutions
  • 1 Pontifical Catholic University of Rio de Janeiro (PUC-Rio)
  • 2 Pontifical Catholic University of Rio de Janeiro
  • 3 Universidade Federal de Juiz de Fora
  • 4 UFJF - Universidade Federal de Juiz de Fora
  • 5 Universidad de Buenos Aires
Track
  • TL03 - Biological and Medicinal Inorganic Chemistry
Keywords
Alzheimer´s disease
Copper
Inclusion complex