Identification and characterization of human interferon alpha inhibitors through a WISH cell line-based reporter gene assay

Interferons (IFNs) are important glycoproteins which can stimulate or inhibit up to three hundred different genes encoding proteins involved in antiviral defense mechanisms, inflammation, adaptive immunity, angiogenesis and among other processes. Nevertheless, different genetic alterations may lead to interferon alpha (IFN-alpha) overproduction in human autoimmune diseases like systemic lupus erythematosus. As a consequence, IFN-alpha is a central molecule whose activity must be regulated to block their harmful effect on those disorders where the endogenous cytokine production constitutes the etiology of the illnesses. In this work, we evaluate the biological activity of eighty-eight compounds, from our own chemo-library, to find potential IFN-alpha inhibitors by using a reporter gene assay (RGA) WISH-Mx2/EGFP. We identified some compounds able to modulate negatively the IFN-alpha activity. The most active IFN-alpha inhibitors were further studied achieving promising results. In addition, some combinations of the most active compounds were analyzed accomplishing a stronger effect to decrease the IFN-alpha activity than each compound alone. Furthermore, the complete inhibition of the cytokine activity was reached with some combinations of compounds.