Marine algal TNF-α inhibitors explored by comparative docking and molecular dynamics simulations

Area of Science:

• Marine natural products chemistry
• Computational drug discovery
• Immunology

Background:

• Marine ecosystems harbor diverse bioactive metabolites with therapeutic potential.
• Tumor necrosis factor-alpha (TNF-α) is a critical pro-inflammatory cytokine implicated in chronic inflammatory conditions like inflammatory bowel disease and rheumatoid arthritis.

Purpose of the Study:

• To identify novel inhibitors of TNF-α from marine algae using integrated computational methods.
• To explore the potential of marine algae-derived compounds as therapeutic agents for inflammatory diseases.

Main Methods:

• Screening of over 2000 marine algae molecules from CMNPD and NPASS databases based on reactivity and molecular weight.
• Pharmacophore-based molecular docking to identify key TNF-α target residues (Glu116, Pro117, Tyr119).
• Molecular dynamics (MD) simulations and MM/PBSA analysis to assess binding affinity and stability of candidate inhibitors.

Main Results:

• CHEMBL510230 (brown algae) and Floridoside (red algae) were identified as promising TNF-α inhibitors.
• Both compounds demonstrated specific and effective targeting of critical TNF-α residues, particularly Tyr119.
• MM/PBSA analysis indicated favorable binding affinities, with Floridoside showing stronger average affinity and CHEMBL510230 exhibiting broader stable interactions.

Conclusions:

• Bioactive compounds from marine algae, such as CHEMBL510230 and Floridoside, show significant potential for inhibiting TNF-α.
• These compounds warrant further preclinical investigation as novel therapeutic candidates for inflammatory diseases.