Biological Evaluation and In Silico Study of Benzoic Acid Derivatives from Bjerkandera adusta Targeting Proteostasis Network Modules
by
Katerina Georgousaki 1, Nikolaos Tsafantakis 1, Sentiljana Gumeni 2
, George Lambrinidis 3, Victor González-Menéndez 4, Jose R. Tormo 4, Olga Genilloud 4, Ioannis P. Trougakos 2 and Nikolas Fokialakis 1,*
Katerina Georgousaki 1, Nikolaos Tsafantakis 1, Sentiljana Gumeni 2, George Lambrinidis 3, Victor González-Menéndez 4, Jose R. Tormo 4, Olga Genilloud 4, Ioannis P. Trougakos 2 and Nikolas Fokialakis 1,*
1
Division of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, 157 71 Athens, Greece
2
Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, 157 72 Athens, Greece
3
Division of Pharmaceutical Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, 157 84 Athens, Greece
4
Fundacion MEDINA, Health Sciences Technology Park, 18016 Granada, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Molecules 2020, 25(3), 666; https://doi.org/10.3390/molecules25030666
Received: 18 December 2019 / Revised: 24 January 2020 / Accepted: 29 January 2020 / Published: 4 February 2020
(This article belongs to the Special Issue Analytical Microbiology)
A main cellular functional module that becomes dysfunctional during aging is the proteostasis network. In the present study, we show that benzoic acid derivatives isolated from Bjerkandera adusta promote the activity of the two main protein degradation systems, namely the ubiquitin-proteasome (UPP) and especially the autophagy-lysosome pathway (ALP) in human foreskin fibroblasts. Our findings were further supported by in silico studies, where all compounds were found to be putative binders of both cathepsins B and L. Among them, compound 3 (3-chloro-4-methoxybenzoic acid) showed the most potent interaction with both enzymes, which justifies the strong activation of cathepsins B and L (467.3 ± 3.9%) on cell-based assays. Considering that the activity of both the UPP and ALP pathways decreases with aging, our results suggest that the hydroxybenzoic acid scaffold could be considered as a promising candidate for the development of novel modulators of the proteostasis network, and likely of anti-aging agents.
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Keywords:
fungi; Bjerkandera adusta; benzoic acid derivatives; cathepsins activity; molecular docking; proteasome activity
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MDPI and ACS Style
Georgousaki, K.; Tsafantakis, N.; Gumeni, S.; Lambrinidis, G.; González-Menéndez, V.; Tormo, J.R.; Genilloud, O.; Trougakos, I.P.; Fokialakis, N. Biological Evaluation and In Silico Study of Benzoic Acid Derivatives from Bjerkandera adusta Targeting Proteostasis Network Modules. Molecules 2020, 25, 666.
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