Conclusion
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.
Methods
Trolox equivalent antioxidant capacity (TEAC), 2',7'-dichlorofluorescein (DCF), thermotolerance assays, C. elegans lifespan analyses. Key findings: 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.