Fullerenes and their derivatives as inhibitors of tumor necrosis factor-α with highly promoted affinities.

摘要: Tumor necrosis factor-α (TNF-α) is a cell signalling protein involved in systemic inflammation infectious and other malignant diseases. Physiologically, it plays an important role regulating host defence, but its overexpression can lead to serious illnesses including cancer, autoimmune disease inflammatory disease. Gadolinium-based metallofullerenols, e.g., Gd@C82(OH) x (x ≈ 22), are well known for their abundant biological activities with low toxicity experimentally theoretically; however, activity direct TNF-α inhibition has not been explored. In this work, we investigated the inhibiting effects of four types fullerene-based ligands: fullerenes, fullerenols, metallofullerenes, metallofullerenols. We reported previously that metallofullerenes hydroxylated derivatives (fullerenols) reside same pocket dimer as SPD304-a inhibitor [He et al. (2005) Science 310:1022, 18]. Ligand docking binding free energy calculations suggest that, similar nonpolar interaction dominated pattern, ligands, C60, C60(OH)12, Gd@C60, C82, C82(OH)12, Gd@C82, Gd@C82(OH)13 Gd@C82(OH)21, have larger affinity than currently inhibitors, could be used design novel inhibitors future. Graphical Abstract Fullerene-material/TNF-α.