In Silico Study on 5-hydroxy-2-(4-hydroxyphenyl)-6,7- dimethoxychromen-4-one as a Candidate IL-1R and TNF-R Inhibitor
DOI:
https://doi.org/10.11113/jomalisc.v3.79Keywords:
5-hydroxy-2-(4-hydroxyphenyl)-6,7-dimethoxychromen-4-one, IL-1R, TNF-R, anti-inflammatory agentsAbstract
Inflammation is an important process that fights infections and allows the repair of tissues; however, chronic inflammation is implicated in many diseases, including autoimmune diseases and tumorigenesis. Central to this process are the Interleukin-1 receptor and Tumor Necrosis Factor receptor that mediate the action of the pro-inflammatory cytokines IL-1 and TNF-α, respectively. This work is aimed at the theoretical investigation of the possibility of 5-Hydroxy-2-(4-hydroxyphenyl)-6,7-dimethoxychromen-4-one, a naturally occurring flavonoid with established anti-inflammatory properties, acting as an IL-1R and TNF-R inhibitor by in silico methods. In fact, molecular docking studies have indicated good binding affinities and identified crucial interactions with amino acid residues in the receptor binding sites. These observations strongly suggest that this compound is likely to inhibit IL-1R and TNF-R with high efficiency, leading to the modulation of the inflammation-related pathways. Further experimental validation is required to confirm these interactions and also to assess their therapeutic potential in inflammatory disorders.
References
Abdulkhaleq, L. A., Assi, M. A., Abdullah, R., Zamri-Saad, M., Taufiq-Yap, Y. H., & Hezmee, M. N. M. (2018). The crucial roles of inflammatory mediators in inflammation: A review. Veterinary World, 11(5), 627. https://doi.org/10.14202/vetworld.2018.627-635
Bustos-Salgado, P., Andrade-Carrera, B., Domínguez-Villegas, V., Díaz-Garrido, N., Rodríguez-Lagunas, M. J., Badía, J., ... & Garduño-Ramírez, M. L. (2021). Screening anti-inflammatory effects of flavanones solutions. International Journal of Molecular Sciences, 22(16), 8878. https://doi.org/10.3390/ijms22168878
Chagas, M. D. S. S., Behrens, M. D., Moragas-Tellis, C. J., Penedo, G. X. M., Silva, A. R., & Gonçalves-de-Albuquerque, C. F. (2022). Flavonols and flavones as potential anti‐inflammatory, antioxidant, and antibacterial compounds. Oxidative Medicine and Cellular Longevity, 2022, 9966750. https://doi.org/10.1155/2022/9966750
Chang, Y., Hawkins, B. A., Du, J. J., Groundwater, P. W., Hibbs, D. E., & Lai, F. (2023). A guide to in silico drug design. Pharmaceutics, 15(1), 49. https://doi.org/10.3390/pharmaceutics15010049
Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., ... & Zhao, L. (2018). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204–7218. https://doi.org/10.18632/oncotarget.23208
Dhillon, B., Aleithan, F., Abdul-Sater, Z., & Abdul-Sater, A. A. (2019). The evolving role of TRAFs in mediating inflammatory responses. Frontiers in Immunology, 10, 104. https://doi.org/10.3389/fimmu.2019.00104
Emami, S., & Ghanbarimasir, Z. (2015). Recent advances of chroman-4-one derivatives: Synthetic approaches and bioactivities. European Journal of Medicinal Chemistry, 93, 539–563. https://doi.org/10.1016/j.ejmech.2015.02.057
Ferrero-Miliani, L., Nielsen, O. H., Andersen, P. S., & Girardin, S. (2007). Chronic inflammation: Importance of NOD2 and NALP3 in interleukin-1β generation. Clinical & Experimental Immunology, 147(2), 227–235. https://doi.org/10.1111/j.1365-2249.2006.03261.x
García-Lafuente, A., Guillamón, E., Villares, A., Rostagno, M. A., & Martínez, J. A. (2009). Flavonoids as anti-inflammatory agents: Implications in cancer and cardiovascular disease. Inflammation Research, 58(9), 537–552. https://doi.org/10.1007/s00011-009-0037-3
Kany, S., Vollrath, J. T., & Relja, B. (2019). Cytokines in inflammatory disease. International Journal of Molecular Sciences, 20(23), 6008. https://doi.org/10.3390/ijms20236008
Mantovani, A., Dinarello, C. A., Molgora, M., & Garlanda, C. (2019). IL-1 and related cytokines in innate and adaptive immunity in health and disease. Immunity, 50(4), 778–795. https://doi.org/10.1016/j.immuni.2019.03.012
Zhang, T., Ma, C., Zhang, Z., Zhang, H., & Hu, H. (2021). NF‐κB signaling in inflammation and cancer. MedComm, 2(4), 618–653. https://doi.org/10.1002/mco2.81
Lim, H., Heo, M. Y., & Kim, H. P. (2019). Flavonoids: Broad spectrum agents on chronic inflammation. Biomolecules & Therapeutics, 27(3), 241–253. https://doi.org/10.4062/biomolther.2018.176
Min, S. Y., Park, C. H., Yu, H. W., & Park, Y. J. (2021). Anti-inflammatory and anti-allergic effects of saponarin and its impact on signaling pathways of RAW 264.7, RBL-2H3, and HaCaT cells. International Journal of Molecular Sciences, 22(16), 8431. https://doi.org/10.3390/ijms22168431
Safe, S., Jayaraman, A., Chapkin, R. S., Howard, M., Mohankumar, K., & Shrestha, R. (2021). Flavonoids: Structure–function and mechanisms of action and opportunities for drug development. Toxicological Research, 37(2), 147–162. https://doi.org/10.1007/s43188-021-00063-6
Tahtinen, S., Tong, A. J., Himmels, P., Oh, J., Paler-Martinez, A., Kim, L., ... & Freund, E. C. (2022). IL-1 and IL-1ra are key regulators of the inflammatory response to RNA vaccines. Nature Immunology, 23(4), 532–542. https://doi.org/10.1038/s41590-022-01159-1
Zhang, H., Liu, X., Cheng, W., Wang, T., & Chen, Y. (2024). Prediction of drug-target binding affinity based on deep learning models. Computers in Biology and Medicine, 108435. https://doi.org/10.1016/j.compbiomed.2024.108435
