AUTHOR=Dzierzbicka Krystyna , Skrzypkowska Maria , Gensicka-Kowalewska Monika , Daśko Mateusz , Słomiński Bartosz 

TITLE=New analogs of 5-substituted-2(1H)-pyridone containing of natural amino acids as potential drugs in idiopathic pulmonary fibrosis. Investigation in silico and preliminary in vitro

JOURNAL=Acta Biochimica Polonica

VOLUME=Volume 72 - 2025

YEAR=2025

URL=https://www.frontierspartnerships.org/journals/acta-biochimica-polonica/articles/10.3389/abp.2025.15218

DOI=10.3389/abp.2025.15218

ISSN=1734-154X

ABSTRACT=The aim of our work was to analyze new functionalized analogues of 5-substituted-2(1H)-pyridone containing of natural amino acids derivatives as a potential drugs in idiopathic pulmonary fibrosis (IPF). The creation of connections with natural amino acids was aimed at obtaining anti-fibrotic compounds with better water solubility, increased hydrophilicity, lower toxicity and better pharmacokinetic properties. For the docking studies the corresponding grid box parameters were used: PARPγ, ALK5 andp38. During our initial research we have synthesized and performed biological in vitro studies for two analogues selected on the basis of molecular modeling: 6b and 6f. MTT test have been performed to select concentrations of PFD derivatives for subsequent analysis. We have analyzed HLA-DR and CXCR4 expression on fibroblasts and 24 h migration of TGF-β1-stimulated fibroblasts. We have also explored proliferation and production of TGF-β1 as well as IL-17 by CD3/CD28 beads-stimulated PBMCs. Preliminary studies show that the designed compounds exhibit promising potential as anti-fibrotic therapeutics. Therefore, their activity is worth further exploring.