A New Cu2+-Binding Isoxazole‑Based N‑Acylhydrazone as a MAO-B Inhibitor: Dual Activity for the Management of Neurodegenerative Diseases

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Abstract

Synthesis and evaluation of MIXX1, a new isoxazole-derived ligand, as a multitarget candidate for Alzheimer's disease treatment. MIXX1 selectively inhibits MAO-B (45.4% at 100 µM) over MAO-A (3.2%), and acts as a Cu(II) chelator, forming an ML₂ complex as revealed by spectroscopic titration. This metal-binding ability suggests MIXX1 could compete with β-amyloid peptides for Cu²⁺ ions, potentially suppressing ROS generation. The combination of selective enzyme inhibition and metal attenuation highlights MIXX1 as a promising scaffold for further development in neurodegenerative disease management.

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Institutions
  • 1 Pontifical Catholic University of Rio de Janeiro (PUC-Rio)
  • 2 Pontifical Catholic University of Rio de Janeiro
  • 3 Pontifical Catholic University of Rio de Janeiro | (Pontifical Catholic University of Rio de Janeiro)
  • 4 PUC-RIO
  • 5 Centro Brasileiro de Pesquisas Físicas | (Brazilian Center for Research in Physics)
  • 6 Universidad de Buenos Aires
Track
  • TL03 - Biological and Medicinal Inorganic Chemistry
Keywords
Alzheimer’s disease
Copper
MAO-B inhibitor