title: The resveratrol derivatives trans-3,5-dimethoxy-4-fluoro-4'-hydroxystilbene and trans-2,4',5-trihydroxystilbene decrease oxidative stress and prolong lifespan in Caenorhabditis elegans.
abstract: OBJECTIVE
  Resveratrol (trans-3,4',5-trihydroxystilbene (1)) was previously shown to extend the lifespan of different model organisms. However, its pharmacological efficiency is controversially discussed. Therefore, the bioactivity of four newly synthesized stilbenes (trans-3,5-dimethoxy-4-fluoro-4'-hydroxystilbene (3), trans-4'-hydroxy-3,4,5-trifluorostilbene (4), trans-2,5-dimethoxy-4'-hydroxystilbene (5), trans-2,4',5-trihydroxystilbene (6)) was compared to (1) and pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene (2)) in the established model organism Caenorhabditis elegans.
  
  
  METHODS
  Trolox equivalent antioxidant capacity (TEAC), 2',7'-dichlorofluorescein (DCF), thermotolerance assays, C. elegans lifespan analyses.
  
  
  RESULTS
  All compounds exert a strong in-vitro radical scavenging activity (6 > 1 > 5 > 2 = 3 = 4), but in vivo, only (3) and (6) reduce reactive oxygen species (ROS) accumulation. Furthermore, (3) and (6) increased the mobility of aged nematodes and prolonged their mean lifespans, while these compounds decreased the thermal stress resistance. Using daf-16 (FoxO), skn-1 (Nrf2) and sir-2.1 (sirtuin) loss-of-function mutant strains, the in vivo antioxidant effects of compounds (3) and (6) were abolished, showing the necessity of these evolutionary highly conserved factors. However, short-time treatment with stilbenes (3) and (6) did not modulate the cellular localization of the transcription factors DAF-16 and SKN-1.
  
  
  CONCLUSIONS
  In contrast to resveratrol, the synthetic stilbene derivatives (3) and (6) increase the lifespan of C. elegans, rendering them promising candidates for pharmacological anti-ageing purposes.
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Fischer
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Büchter
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Karoline
authors.initials: K
authors.lastname: Koch
authors.affiliation: Institute of Chemistry, Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Albert
authors.affiliation: Institute of Chemistry, Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Csuk
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Wim
authors.initials: W
authors.lastname: Wätjen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006358:Hot Temperature; D008136:Longevity / Q000187:drug effects*; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000494:pharmacology*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D013267:Stilbenes; D014157:Transcription Factors; C000618773:trans-2,4',5-trihydroxystilbene; C000618772:trans-3,5-dimethoxy-4-fluoro-4'-hydroxystilbene; D000077185:Resveratrol
keywords: Nrf2; ageing; insulin-signalling; oxidative stress; secondary plant compounds