Evaluating the Anti-tumor and Anti-inflammatory Efficacy of Natural Compounds Targeting TNFRs Using Computational Methods.

Abstract

Introduction/objectives: The tumor necrosis factor (TNF) superfamily includes cytokines that play a role in biological functions such as cell cycle regulation, cell death, and inflammatory responses. The main objective of this research is to investigate the effects of naturally occurring compounds on the TNF receptor family using in silico methods, thereby revealing their potential for anticancer and anti-inflammatory activity.

Methods: In this study, the drug affinity, receptor interactions, and pharmacokinetic properties of the compounds used were evaluated, and the analysis was completed with molecular docking, molecular dynamics simulations, and binding free energy calculations.

Results: Computational analyses revealed that boswellic acid forms strong and stable interactions with TNFR1, TNFR2, and CD95. Berberine was identified as another candidate showing strong affinity with CD40. The analyses suggest that cysteine-rich key structural regions play a significant role in the stability of ligand-receptor complexes.

Discussions: The data obtained in our study indicate that boswellic acid and berberine have the ability to interact with TNFRs and affect multiple targets. The previously reported antiinflammatory and anti-cancer properties of these compounds are consistent with our current findings. On the other hand, the possibility that the in silico approaches used may not fully reflect the receptor activation processes or unexpected interactions should not be overlooked. Therefore, the results obtained at this stage must be confirmed by experimental methods.

Conclusions: The analysis results indicate that boswellic acid and berberine, which possess anti- inflammatory and anticancer properties, can be multi-target agents by interacting with the TNFR family.