The resveratrol derivatives trans-3,5-dimethoxy-4-fluoro-4'-hydroxystilbene and trans-2,4',5-trihydroxystilbene...

Area of Science:

• Biochemistry and Molecular Biology
• Gerontology
• Pharmacology

Background:

• Resveratrol is known to extend lifespan in model organisms, but its pharmacological efficiency is debated.
• Novel stilbene derivatives were synthesized to investigate their bioactivity and compare them to resveratrol and pterostilbene.
• Caenorhabditis elegans is a well-established model organism for aging research.

Purpose of the Study:

• To compare the bioactivity of four newly synthesized stilbenes with resveratrol and pterostilbene.
• To evaluate the in vitro and in vivo effects of these compounds on aging processes in C. elegans.
• To identify potential pharmacological candidates for anti-aging purposes.

Main Methods:

• In vitro antioxidant capacity assays (TEAC).
• In vivo assays including reactive oxygen species (ROS) measurement (DCF), thermotolerance, and lifespan analysis in C. elegans.
• Utilized loss-of-function mutant strains (daf-16, skn-1, sir-2.1) to elucidate mechanisms of action.

Main Results:

• All tested stilbenes exhibited strong in vitro radical scavenging activity.
• In vivo, compounds (3) and (6) effectively reduced ROS accumulation and increased mobility in aged nematodes.
• Compounds (3) and (6) prolonged mean lifespans in C. elegans, but decreased thermal stress resistance.
• The antioxidant effects of (3) and (6) in vivo were dependent on conserved factors like DAF-16, SKN-1, and SIR-2.1, though they did not alter transcription factor localization.

Conclusions:

• Synthetic stilbene derivatives (3) and (6) significantly increase lifespan in C. elegans.
• These novel compounds demonstrate greater efficacy than resveratrol in this model organism.
• Stilbenes (3) and (6) represent promising candidates for pharmacological anti-aging interventions.