Network pharmacology and molecular docking insights into Sirtuin-2 inhibitors (AK-7 and AGK-2): A synergistic strategy for COPD treatment

Abstract

Objective

In the present study network pharmacology analysis of AGK-2 and AK-7 (SIRT-2 inhibitors) were performed to elucidate their mechanism in regulating COPD pathogenesis.

Methods

Different database (Swiss Target Prediction, GeneCards and DisGeNet) were used for predicting targets of compound and disease. Drug-Target network was constructed using Cytoscape while functional enrichment and pathway analyses were performed using STRING database. ShinnyGo database was utilized for Annotation, Visualization, and Integrated Discovery, along with Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG). Molecular docking was performed to assess the binding affinities of AGK-2 and AK-7 to key proteins.

Results

AK-7 and AGK2 revealed 43 and 41 targets while 3392 targets related to COPD were found. Protein-protein interaction (PPI) network revealed 43 nodes and 133 edges for AK-7 and 41 nodes and 110 edges for AGK-2. Enrichment analysis highlighted distinct involvement of AGK-2 and AK-7 in various aspects of respiratory physiology including molecular signaling and neuronal secretions. AGK-2 revealed to influence pathways as EGFR and Ras/Raf/MAPK, while AK-7 targeted pathways like nitric oxide synthatase and tuberculosis, as well as regulating calcium signaling and neuro-immune interactions associated with COPD. Finally molecular docking revealed that AGK-2 showed good binding affinity with MAPK14 and STAT3. Whereas AK-7 with CASP3 and CXCL8. The findings highlight potency of AGK-2 and AK-7 in modulating inflammation, reactive oxygen species, and neuroimmune interactions, suggesting their efficacy in COPD management through SIRT-2 regulation.

Conclusion

The study offers novel insights into the potential of SIRT-2 inhibitors to modulate disease mechanisms at a molecular level.