Securinine Derivatives as Potential Anti-amyloid Therapeutic Approach.
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.


CONCLUSIONS
Based on these results, aminoderivatives of securinine scaffold are promising compounds for development of new drugs for the treatment of neurodegenerative diseases.
Institute of Physiologically Active Compounds of Russian Academy of Science, Chernogolovka. Russian Federation.
Margarita E
ME
Neganova
Institute of Physiologically Active Compounds of Russian Academy of Science, Chernogolovka. Russian Federation.
Sergei G
SG
Klochkov
Institute of Physiologically Active Compounds of Russian Academy of Science, Chernogolovka. Russian Federation.
Ludmila N
LN
Petrova
Institute of Physiologically Active Compounds of Russian Academy of Science, Chernogolovka. Russian Federation.
Elena F
EF
Shevtsova
Institute of Physiologically Active Compounds of Russian Academy of Science, Chernogolovka. Russian Federation.
Svetlana V
SV
Afanasieva
Institute of Physiologically Active Compounds of Russian Academy of Science, Chernogolovka. Russian Federation.
Ekaterina S
ES
Chudinova
I.M. Sechenov First Moscow State Medical University, Moscow. Russian Federation.
Vladimir P
VP
Fisenko
Institute of Physiologically Active Compounds of Russian Academy of Science, Chernogolovka. Russian Federation.
Sergei O
SO
Bachurin
Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogota D.C.. Colombia.
George E
GE
Barreto
"GALLY" International Biomedical Research Consulting LLC, 7733 Louis Pasteur Drive, #330, San Antonio, TX 78229. United States.
Gjumrakch
G
Aliev
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000627:therapeutic use*; D001381:Azepines / Q000737:chemistry* / Q000627:therapeutic use*; D006572:Heterocyclic Compounds, Bridged-Ring / Q000737:chemistry* / Q000627:therapeutic use*; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000627:therapeutic use*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry* / Q000627:therapeutic use*; D051381:Rats
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001381:Azepines; D006572:Heterocyclic Compounds, Bridged-Ring; D007783:Lactones; D010446:Peptide Fragments; D010880:Piperidines; C075222:amyloid beta-protein (1-42); C000785:securinine
Alkaloids; antioxidant; lipid peroxidation; neurodegenerative diseases; neuroprotection; securinine; μ-amyloid