Reactivity of diphenylpropynone derivatives toward metal-associated amyloid-ß species.
Inorg Chem
; 51(23): 12959-67, 2012 Dec 03.
Article
in En
| MEDLINE
| ID: mdl-23153071
ABSTRACT
In Alzheimer's disease (AD), metal-associated amyloid-ß (metal-Aß) species have been suggested to be involved in neurotoxicity; however, their role in disease development is still unclear. To elucidate this aspect, chemical reagents have been developed as valuable tools for targeting metal-Aß species, modulating the interaction between the metal and Aß, and subsequently altering metal-Aß reactivity. Herein, we report the design, preparation, characterization, and reactivity of two diphenylpropynone derivatives (DPP1 and DPP2) composed of structural moieties for metal chelation and Aß interaction (bifunctionality). The interactions of these compounds with metal ions and Aß species were confirmed by UV-vis, NMR, mass spectrometry, and docking studies. The effects of these bifunctional molecules on the control of in vitro metal-free and metal-induced Aß aggregation were investigated and monitored by gel electrophoresis and transmission electron microscopy (TEM). Both DPP1 and DPP2 showed reactivity toward metal-Aß species over metal-free Aß species to different extents. In particular, DPP2, which contains a dimethylamino group, exhibited greater reactivity with metal-Aß species than DPP1, suggesting a structure-reactivity relationship. Overall, our studies present a new bifunctional scaffold that could be utilized to develop chemical reagents for investigating metal-Aß species in AD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organometallic Compounds
/
Benzhydryl Compounds
/
Amyloid beta-Peptides
/
Alkynes
/
Metals
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Inorg Chem
Year:
2012
Document type:
Article
Affiliation country: