Securinine derivatives as potential anti-amyloid therapeutic approach
Neganova M. E., Klochkov S. G., Petrova L. N., Shevtsova E. F., Afanasieva S. V., Chudinova E. S., Fisenko V. P., Bachurin S. O., Barreto G. E., Aliev G.
CNS & Neurological Disorders - Drug Targets
Vol.16, Issue3, P. 351-355
Опубликовано: 2017
Тип ресурса: Статья
DOI:10.2174/1871527315666161107090525
Аннотация:
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 β-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. © 2017 Bentham Science Publishers.
Ключевые слова:
Alkaloids; Antioxidant; Lipid peroxidation; Neurodegenerative diseases; Neuroprotection; Securinine; β-amyloid
amyloid beta protein; antioxidant; securinine; amyloid beta protein; amyloid beta-protein (1-42); antioxidant; azepine derivative; fused heterocyclic rings; lactone; peptide fragment; piperidine derivative; securinine; animal experiment; antioxidant activity; Article; degenerative disease; fluorescence analysis; high performance liquid chromatography; IC50; lipid peroxidation; male; nonhuman; nuclear magnetic resonance spectroscopy; oxidative stress; rat; Alzheimer disease; amyloidosis; animal; chemistry; drug effect; human; metabolism; oxidative stress; Alzheimer Disease; Amyloid beta-Peptides; Amyloidosis; Animals; Antioxidants; Azepines; Heterocyclic Compounds, Bridged-Ring; Humans; Lactones; Male; Oxidative Stress; Peptide Fragments; Piperidines; Rats
Язык текста: Английский
ISSN: 1996-3181
Neganova M. E.
Klochkov S. G.
Petrova L. N.
Shevtsova E. F.
Afanasieva S. V.
Chudinova E. S.
Fisenko V. P. Vladimir Petrovich 1946-
Bachurin S. O.
Barreto G. E.
Aliev G. Gyumrakh 1958-
Неганова М. Е.
Клочков С. Г.
Петрова Л. Н.
Шевцова Е. Ф.
Афанасиева С. В.
Чудинова Е. С.
Фисенко В. П. Владимир Петрович 1946-
Бачурин С. О.
Баррето Г. Е.
Алиев Г. Гюмрах 1958-
Securinine derivatives as potential anti-amyloid therapeutic approach
Текст визуальный непосредственный
CNS & Neurological Disorders - Drug Targets
Bentham Science Publishers
Vol.16, Issue3 P. 351-355
2017
Статья
Alkaloids Antioxidant Lipid peroxidation Neurodegenerative diseases Neuroprotection Securinine β-amyloid
amyloid beta protein antioxidant securinine amyloid beta protein amyloid beta-protein (1-42) antioxidant azepine derivative fused heterocyclic rings lactone peptide fragment piperidine derivative securinine animal experiment antioxidant activity Article degenerative disease fluorescence analysis high performance liquid chromatography IC50 lipid peroxidation male nonhuman nuclear magnetic resonance spectroscopy oxidative stress rat Alzheimer disease amyloidosis animal chemistry drug effect human metabolism oxidative stress Alzheimer Disease Amyloid beta-Peptides Amyloidosis Animals Antioxidants Azepines Heterocyclic Compounds, Bridged-Ring Humans Lactones Male Oxidative Stress Peptide Fragments Piperidines Rats
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 β-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. © 2017 Bentham Science Publishers.