Artículo de revista
Neuroprotective Effect of a New 7,8-Dihydroxycoumarin-Based Fe2+/Cu2+ Chelator in Cell and Animal Models of Parkinson’s Disease
Fecha
2017Registro en:
ACS Chemical Neuroscience, Volumen 8, Issue 1, 2018, Pages 178-185
19487193
10.1021/acschemneuro.6b00309
Autor
Aguirre, Pabla
García Beltrán, Olimpo
Tapia, Victoria
Muñoz, Yorka
Cassels Niven, Bruce
Núñez González, Marco
Institución
Resumen
© 2016 American Chemical Society.Disturbed iron homeostasis, often coupled to mitochondrial dysfunction, plays an important role in the progression of common neurodegenerative diseases such as Parkinson’s disease (PD). Recent studies have underlined the relevance of iron chelation therapy for the treatment of these diseases. Here we describe the synthesis, chemical, and biological characterization of the multifunctional chelator 7,8-dihydroxy-4-((methylamino)methyl)-2H-chromen-2-one (DHC12). Metal selectivity of DHC12 was Cu2+ ∼ Fe2+ > Zn2+ > Fe3+. No binding capacity was detected for Hg2+, Co2+, Ca2+, Mn2+, Mg2+, Ni2+, Pb2+, or Cd2+. DHC12 accessed cells colocalizing with Mitotracker Orange, an indication of mitochondrial targeting. In addition, DHC12 chelated mitochondrial and cytoplasmic labile iron. Upon mitochondrial complex I inhibition, DHC12 protected plasma membrane and mitochondria against lipid peroxidation, as detected by the reduced formation of 4-hydroxynonenal adducts an