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Biological Evaluation and In Silico Study of Benzoic Acid Derivatives from Bjerkandera adusta Targeting Proteostasis Network Modules

Summary

This research discovered that certain compounds from a wood-decay fungus can help cells maintain better protein quality control, which typically declines as we age. The findings could lead to new anti-aging treatments or therapies for age-related diseases. Impacts on everyday life: • Could lead to new anti-aging supplements or medications • May help develop treatments for age-related diseases • Demonstrates the potential of natural compounds from fungi as therapeutic agents • Could improve understanding of cellular aging processes • May help develop strategies to maintain better health in older age

Background

The proteostasis network, which controls protein synthesis, folding, trafficking and degradation, becomes dysfunctional during aging. The two main protein degradation systems are the ubiquitin-proteasome pathway (UPP) and autophagy-lysosome pathway (ALP), both of which decline in activity with age. Bjerkandera adusta is a wood-rotting basidiomycete known for producing halogenated organic compounds with potential antibiotic effects.

Objective

To investigate benzoic acid derivatives isolated from Bjerkandera adusta for their ability to enhance the activity of protein degradation systems (UPP and ALP) in human foreskin fibroblasts, and evaluate their potential as modulators of the proteostasis network.

Results

Four benzoic acid derivatives were isolated and characterized. Compounds 1, 3, and 4 induced proteasomal activities, with compounds 1 and 3 showing the greatest potential. Compound 3 (3-chloro-4-methoxybenzoic acid) demonstrated the strongest activation of cathepsins B and L (467.3%). Molecular docking showed all compounds were putative binders of both cathepsins, with compound 3 showing the most potent interaction.

Conclusion

The benzoic acid derivatives isolated from B. adusta, particularly compound 3, showed significant potential in enhancing protein degradation pathways. Given that both UPP and ALP activities decrease with aging, these compounds could be promising candidates for developing novel modulators of the proteostasis network and potential anti-aging agents.
  • Published in:Molecules,
  • Study Type:Laboratory Research,
  • Source: 10.3390/molecules25030666
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