Design, synthesis, ADMET analysis of aryl ethers based on 5-nitro indole: Their molecular docking study based on TNF-α with anti-inflammatory activity

A novel series of eleven aryl ethers (S-1-S-11) based on 5-nitroindole were prepared, confirmed, and screened out for their in vitro and in vivo anti-inflammatory response. The prepared aryl ethers were synthesized by reacting 5‑chloro-2-(5-nitro-1H-indol-1-yl) aniline with various phenols in acetonitrile. Structural characterization of all aryl ethers was established and confirmed by FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry. The ADMET studies were carried out by web software. Lipinski's rule of five was applied to find out the drug-likeness property. A docking study was done to emphasize the binding site of the Tumor Necrosis Factor-alpha (TNF-α) and newly synthesized aryl ether compounds. In the series, the synthesized compound showed the highest binding affinity, -10.6 kcal/mol. The prepared aryl ether compounds were evaluated for their anti-inflammatory activity by albumin denaturation inhibitory assay and the carrageenan-induced rat paw edema method. Among them, compound S-7 showed a higher anti-inflammatory effect than indomethacin.