title: Brassinosteroids and analogs as neuroprotectors: synthesis and structure-activity relationships.
abstract: We have demonstrated previously that the brassinosteroid (BR) 24-epibrassinolide exerts neuroprotective effects deriving from its antioxidative properties. In this study, we synthesized 2 natural BRs and 5 synthetic analogs and analyzed their neuroprotective actions in neuronal PC12 cells, against 1-methyl-4-phenylpyridinium (MPP(+)), a neurotoxin known to induce oxidative stress and degenerescence of dopaminergic neurons characteristic of Parkinsonian brains. We also tested the neuroprotective potential of 2 commercially available BRs. Our results disclosed that 6 of the 9 BRs and analogs tested protected neuronal PC12 cells against MPP(+) toxicity. In addition, our structure-activity study suggests that the steroid B-ring and lateral chain play an important role for their neuroprotective action.
authors: Département de Chimie-Biologie, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.
authors: Jihane
authors: J
authors: Ismaili
authors: Martin
authors: M
authors: Boisvert
authors: Fanny
authors: F
authors: Longpré
authors: Julie
authors: J
authors: Carange
authors: Céline
authors: C
authors: Le Gall
authors: Maria-Grazia
authors: MG
authors: Martinoli
authors: Benoit
authors: B
authors: Daoust
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D060406:Brassinosteroids / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D060406:Brassinosteroids; D018696:Neuroprotective Agents; D015655:1-Methyl-4-phenylpyridinium