Securinine Derivatives as Potential Anti-amyloid Therapeutic Approach

Neganova ME, Klochkov SG, Petrova LN, Shevtsova EF, Afanasieva SV, Chudinova ES, Fisenko VP, Bachurin SO, Barreto GE, Aliev G.

Abstract
BACKGROUND:
Oxidative stress and amyloid deposition are tightly interconnected pathological features of Alzheimer disease. In this respect, both amyloid production and aggregation may be stimulated by oxidative stress and also the increase of pathogenic β-amyloid and its aggregated form lead to oxidative stress progression. Therefore, the search for potential drugs with both antioxidant and antiaggregation properties are of great interest.

METHODS:
In this study, we described the stereospecific synthesis of alkaloid securinine aminoderivatives.

RESULTS:
We showed that the newly synthesized compounds possess antioxidant and metal-chelating properties. Indeed, we report that one compound has inhibitory effects towards μ-amyloid aggregation.

CONCLUSION:
Based on these results, aminoderivatives of securinine scaffold are promising compounds for development of new drugs for the treatment of neurodegenerative diseases.

KEYWORDS:
Alkaloids; antioxidant; lipid peroxidation; neurodegenerative diseases; neuroprotection; securinine; μ-amyloid

PMID: 27823572 DOI: 10.2174/1871527315666161107090525

https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=6#135045

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