Exploring the Potential of Natural-like Compounds as TNF-α Inhibitors: An In-silico Approach
Biointerface Research in Applied Chemistry · 2024
Tumor necrosis factor-α (TNF-α) regulates immune cells. Excessive production of TNF-α is associated with various diseases. TNF-α inhibition by antibodies or proteins directed against TNF-α is an accepted therapy for autoimmune diseases. However, the treatment above is expensive, with serious adverse effects. Moreover, no reported chemical inhibitors of TNF-α had been therapeutically successful. Thus, there is a need to explore cheap chemical compounds possessing anti-TNF-α activity with fewer side effects. This study aimed to identify novel natural-like compounds with TNF-α inhibitory activity using in-silico techniques. A library of 210 natural-like compounds was docked against TNF-α (PDB ID-2AZ5) using Glide. Based on the docking scores, the top 20 natural-like compounds with promising binding affinities (docking score <-6.5) were identified and subjected to ADMET profiling using SwissADME and pkCSM. The interactions of the compounds above were further validated by MM-GBSA and molecular dynamics using Prime-MMGBSA and Desmond (Schrödinger). ADMET profiling demonstrated that 7 natural-like compounds had excellent drug-like properties. The MM-GBSA and MD simulations finally revealed that 4 natural-like compounds, i.e., N-[(4Aminophenyl)methyl]adenosine, 5'-N Ethylcarboxamidoadenosine, Trifluridine, and APNEA, have strong protein-ligand interactions thus may act as potential TNF-α inhibitors. This study gives potential evidence for the effectiveness of these natural-like compounds as TNF-α inhibitors.