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Published:
Jul 7, 2021Keywords:
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Main Article Content
Design of dual inhibitors of human TNF-α and IL-6 with potentials for the treatment of rheumatoid arthritis
Abstract
Purpose: To design dual inhibitors of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) with potentials for the treatment of rheumatoid arthritis (RA).
Methods: Tumor necrosis factor α (TNF-α) and IL-6 were investigated as potential drug targets for the treatment of RA. Dual inhibitors targeting both TNF-α and IL-6 were designed simultaneously using molecular docking simulation-based in silico virtual screening technique. National Cancer Institute (NCI) diversity set-II consisting of 1818 diverse ligands were screened against both drug targets in order to identify potential lead molecules on the basis of lowest binding energy.
Results: Out of 1818 diverse ligand molecules present in the NCI diversity set-II, five lead molecules were selected based on best binding interactions with both target receptors. The results of toxicity profiling showed that compounds ZINC19701771 and ZINC06576501 lacked major toxicity-associated functional groups linked to mutagenic, tumorigenic, irritant and reproductive effects. However, ZINC03898665 and ZINC05015095 possessed some mutagenic and reproductive effects. Compound ZINC01757986 also showed a high chance of mutagenicity.
Conclusion: These results indicate that the two lead molecules (ZINC19701771 and ZINC06576501) that showed reliable physicochemical properties can serve as potential candidates for development of anti-arthritis drug for effective inhibition of human TNF-α and IL-6 receptors.
