In silico molecular docking, drug‐likeness and toxicity studies of potential marine compounds from Rhabdastrella provientiae as TNF‐α inhibitors

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Abstract Tumor necrosis factor‐alpha (TNF‐α) is a crucial cytokine that orchestrates inflammatory responses within the immune system. Derived from cells such as macrophages and monocytes, TNF‐α plays a pivotal role in inflammation by binding to its receptors on target cells. This binding initiates a cascade of events, including the production of other pro‐inflammatory cytokines and the recruitment of immune cells to the affected site. While TNF‐α is vital for the body's defense against infections and injuries, its sustained or excessive release can contribute to chronic inflammation and tissue damage. Remarkably, therapeutic interventions aimed at TNF‐α, such as marine compounds, have effectively managed inflammatory conditions like rheumatoid arthritis and inflammatory bowel diseases. Hence, the present study identifies natural compounds sourced from the Rhabdastrella providentiae sponge through in silico screening, involving molecular docking, drug‐likeness analysis, oral toxicity prediction, and density functional theory calculation. Docking simulation results reveal that rhabdastrellin G, rhabdaprovidines G, rhabdastrellin I, rhabdastrellin H and rhabdastrellin K exhibit stronger binding affinity than the reference inhibitor SPD‐304 (ΔG = −8.71 kcal/mol), with ΔG values of −9.583, −9.509, −9.877, −9.196, and −8.892 kcal/mol, respectively. Furthermore, drug‐likeness and oral toxicity analyses indicate that these compounds violate Lipinski's two rules but satisfy criteria for drug‐like natural compounds within the “known drug space” rules. Additionally, the predicted toxicity levels for rhabdastrellin G, rhabdastrellin H and rhabdastrellin K are lower and safer than those of other compounds under investigation. Therefore, rhabdastrellin G, rhabdastrellin H and rhabdastrellin K emerge as three potential candidates for further research in subsequent stages.