title: Neuroprotective Effects of the Securinine-Analogues: 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.
authors: Margarita E
authors: ME
authors: Neganova
authors: Sergei G
authors: SG
authors: Klochkov
authors: Svetlana V
authors: SV
authors: Afanasieva
authors: Tatiana P
authors: TP
authors: Serkova
authors: Ekaterina S
authors: ES
authors: Chudinova
authors: Sergei O
authors: SO
authors: Bachurin
authors: V Prakash
authors: VP
authors: Reddy
authors: "GALLY" International Biomedical Research Consulting LLC, 7733 Louis Pasteur Drive, #330, San Antonio, TX 78229, USA. aliev03@gmail.com.
authors: Gjumrakch
authors: G
authors: Aliev
authors: Elena F
authors: EF
authors: Shevtsova
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D006572:Heterocyclic Compounds, Bridged-Ring / Q000737:chemistry* / Q000494:pharmacology*; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats
chemical_list: D001381:Azepines; D006572:Heterocyclic Compounds, Bridged-Ring; D007783:Lactones; D018696:Neuroprotective Agents; D010880:Piperidines; C000785:securinine