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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Neuroprotective effects of the securinine-analogues: identification of Allomargaritarine as a lead compound

Author(s): Margarita E. Neganova, Sergei G. Klochkov, Svetlana V. Afanasieva, Tatiana P. Serkova, Ekaterina S. Chudinova, Sergei O. Bachurin, V. Prakash Reddy, Gjumrakch Aliev and Elena F. Shevtsova

Volume 15 , Issue 1 , 2016

Page: [102 - 107] Pages: 6

DOI: 10.2174/1871527314666150821111812

Price: $65

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.

Keywords: Neurodegenerative diseases, neuroprotection, mitochondria, lipid peroxidation, antioxidant, alkaloids, lactones.


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