Interaction of quercetin and quinazoline with Interleukin 6 and Janus kinase 3 receptors, therapeutic targets in rheumatoid arthritis: An in silico approach

Objectives Rheumatoid Arthritis (RA) is a serious inflammatory disease seen in adults that affects the autoimmune system. The patients suffer from severe pain which is mainly seen in the joints of hands and legs. A disease so debilitating and agonizing as RA undoubtedly demands the best designed drugs for effective therapy. The existing therapeutic approaches include disease modifying anti rheumatic drugs (DMARDs) of synthetic or biological origin, non-steroidal anti inflammatory drugs and glucocorticoids. Conventional DMARDs include methotrexate and Janus kinase inhibitors while B cell depleting drugs, tumor necrosis factor inhibitors belong to the category of those with biological origin. The present study aims to find the interaction of quercetin and quinazoline, two plant based compounds, with Interleukin 6 (IL-6) and Janus Kinase 3 (JAK3), two therapeutic targets in Rheumatoid Arthritis. Material and Methods The molecules for the study were retrieved from PDB and PubChem databases and the docking was done by Molegro Virtual Docker. Drug likeness and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis were also conducted. Results The ligand Quercetin binds in to the active site of the IL-6 receptor with a MolDock Score of -104.421kcal/mol, interaction energy -116.77kJ/mol and Re-rank score of -51.9427kcal/mol. Docking and ADME results demonstrated that Quercetin, a prominent phytoconstituent present in plants, effectively interacts with this receptor. The prolonged use of synthetic drugs can lead to side effects and thus need to be replaced with therapeutics having no or the least side effects. Conclusion The data substantiates the previous reports supporting the therapeutic worth of quercetin in the therapy of Rheumatoid Arthritis and thus supports its potential as a drug candidate. Quercetin gave better values in the docking analysis than quinazoline. However, further extensive screening through dry lab and wet lab experimentation with the inclusion of more receptors has to be conducted to understand its efficiency.