Cyclen-based chelators for the inhibition of Aβ aggregation: Synthesis, anti-oxidant and aggregation evaluation
- Publication Type:
- Journal Article
- Citation:
- Inorganica Chimica Acta, 2017, 467 pp. 343 - 350
- Issue Date:
- 2017-10-01
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© 2017 Elsevier B.V. The aggregation of the protein amyloid-β in the brain has been associated with neurodegenerative diseases such as Alzheimer's disease. Such aggregation of amyloid-β can be induced by misregulated metal ions such as Cu2+ and Zn2+. Here we present four metal chelating compounds based on the cyclen macrocycle that each bear a pendant arm to provide additional anti-oxidant activity. The corresponding Cu2+, Zn2+ and Ni2+ complexes have been synthesized and characterized to examine the ability of the chelators to bind to the metal centres. Aβ40 de-aggregation by the cyclen compounds was assessed using turbidometry and the re-solubilization of the Aβ40 was also examined. Our results show that the cyclen compounds have the ability to effectively chelate Cu2+ and Zn2+ metal ions and thus de-aggregate Aβ40 that has been aggregated due to the presence of these ions. The antioxidant properties of the cyclen compounds were tested by using the DPPH scavenging assay and the results show that some of the compounds can decrease oxidative stress.
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