Molecular docking of selected phytoconstituents with signaling molecules of Ultraviolet-B induced oxidative damage

Area of Science:

• Molecular biology and photochemistry
• Natural product chemistry
• Computational drug discovery

Background:

• Tumor progression and chemoresistance are linked to disrupted signaling pathways involving TNF-α, AP-1, and NF-κB.
• Phytoconstituents offer a promising avenue for cancer treatment by modulating biological activities through signaling pathway interactions.
• UVB-induced photodamage involves complex stress signaling pathways that can be targeted by natural compounds.

Purpose of the Study:

• To investigate the binding interactions between specific phytoconstituents and key signaling molecules (TNF-α, AP-1, NF-κB).
• To identify potential therapeutic agents from plant-derived compounds for mitigating UVB-induced photodamage.
• To explore the molecular mechanisms underlying the protective effects of phytoconstituents against UV radiation.

Main Methods:

• Induced fit docking simulations were employed to analyze binding conformations.
• Four phytoconstituents (pantothenic acid, gallic acid, madecassic acid, palmitic acid ethyl ester) were docked against TNF-α, AP-1, and NF-κB.
• Analysis of interacting residues and binding poses was performed to identify favorable interactions.

Main Results:

• Favorable binding conformations were observed between the selected phytoconstituents and the target signaling molecules.
• Specific binding poses and common interacting residues were identified for each ligand-protein complex.
• The study identified the most effective phytoconstituents as potential ligands for TNF-α, AP-1, and NF-κB.

Conclusions:

• The studied phytoconstituents, particularly gallic acid and pantothenic acid, demonstrate significant potential for ameliorating UVB-induced photodamage.
• These findings suggest that targeting TNF-α, AP-1, and NF-κB with specific plant-derived compounds could be a viable strategy for photoprotection.
• Further research into these phytoconstituents may lead to the development of novel therapeutic agents for skin damage prevention and treatment.