Neuroprotective Effects of the Securinine-Analogs: Identification of Allomargaritarine as a Lead Compound

Abstract

Oxidative stress and mitochondrial disturbances are the common and important causative factors of aging, and play an important role in the late onset of sporadic neurodegenerative diseases, including Alzheimer disease (AD). Furthermore, emerging evidence from in vitro and in vivo disease models suggests that oxidative stress and increased vulnerability to induction of mitochondrial permeability transition leads to the pathogenesis of the neurological disorders. Towards the goals of developing effective neuroprotectors, this article describes the synthesis and neuroprotective studies of various derivatives of the naturally occurring alkaloid securinine, based on which a lead compound, allomargaritarine (a diastereomer of margaritarine), was identified as an effective therapeutic for neuroprotection. Allomargaritarine exhibits high antioxidant activity, and has significant mitoprotective effect on cellular models of neurodegeneration.

Department(s)

Chemistry

Keywords and Phrases

Alkaloid Derivative; Allomargaritarine; Plant Medicinal Product; Securinine; Securinine Derivative; Unclassified Drug; Aging; Alzheimer Disease; Animal Cell; Animal Tissue; Antioxidant Activity; Cell Survival; Controlled Study; Disorders of Mitochondrial Functions; Drug Synthesis; Lipid Peroxidation; Male; Mitochondrial Membrane Potential; Mitochondrial Permeability; MTT Assay; Nerve Degeneration; Neuroprotection; Newborn; Nonhuman; Oxidative Stress; Rat; Ultraviolet Spectroscopy

International Standard Serial Number (ISSN)

1871-5273

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2016 Bentham Science Publishers B.V., All rights reserved.

Publication Date

01 Feb 2016

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