In silico molecular docking and ADMET study of Isodon coetsa phytochemicals targeting TNF-α in inflammation-mediated diseases

Abstract

In inflammatory diseases, the expression of the target protein tumor necrosis factor-alpha (TNF-α) plays a crucial role in the pathogenesis and development of certain conditions, such as autoimmune diseases, rheumatoid arthritis, inflammatory bowel disease, and psoriatic arthritis. TNF-α inhibitors have several limitations. Screening studies of plant-derived compounds have shown promising results due to their lower incidence of side effects and reasonable cost. Therefore, this research focuses on identifying compounds isolated from Isodon coetsa, collected from previous studies, that exhibit inhibitory effects on TNF-α through computational methods such as molecular docking and ADMET prediction. Among the compounds binding to the active site of TNF-α, five diterpenoids, namely 2α,3α,24-trihydroxy-11α,12α-epoxy-urs-20(30)-en-28,13β-olide,2α,3α,24-trihydroxy-12,20(30)-ursadien-28-oic acid, xerophilusin B, oridonin, and 15α-hydroxy-6,7-seco-1α,7:11α,6-diolide-ent-kaur-16-en, exhibited higher binding affinity than the reference inhibitor SPD-304. All the potential compounds predicted by ADME demonstrated favorable pharmacokinetic properties. Moreover, regarding the toxicity of the I. coetsa derived compounds, namely 2α,3α,24-trihydroxy-11α,12α-epoxy-urs-20(30)-en-28,13β-olide, xerophilusin B, and 15α-hydroxy-6,7-seco-1α,7:11α,6-diolide-ent-kaur-16-en, they exhibited low toxicity and safety for oral administration. Hence, these compounds may serve as potential candidates to replace the inhibitor SPD-304 as important therapeutic agents against TNF-α in the future. The results obtained need to be further investigated through in-depth in vitro and in vivo experiment studies.