Interferon induction: New approaches in generating functional inductors

Interferons type (IFN-a/p) I are the most important factors of a body defense against viral and bacterial infections. Indeed, these proteins induction create first line of protection against infections and due to these functions are used in medical practice for treatment of acute and chronic viral diseases. However, long-term application of a recombinant IFN-a/p leads to understanding of practical demand of interferon inducers. Physiological induction of endogenous IFN-a/p have evident preference in comparison with injection of a recombinant IFN-a/p preparations in high dosages, as it’s apply usually in treatment of hepatitis C or cancer. Physiological induction of IFN-a/p is based on utilization of a natural pathways of activation of IFN-a/p gene’s expression, specific set of cellular receptors and cellular signal systems, involved in genetic control of innate immune response. Therefore, for development of a new approaches in creation of an interferon inducers fun­damental research had been needed in a field of physiological pathways of interferon regulation and mecha­nisms of down regulation and inhibition of a cellular antiviral defense. IFN type I and II have the main contri­bution in this defense as a key factors of innate immune response. As a result of these studies structure and function of IFN-a/p, their genes, IFN-a/p - receptor interaction, and intracellular signaling cascade involved in gene regulation are deciphered.

Among leading IFN-inductors are dibasol, imiquimod, cycloferon and ds-RNA preparations synthetic and natural origin. Benzimidazole derivatives had been studied in the Institute of Experimental medicine from 50^th years till 70^th. As a result of these studies dibasol and imiquimod analogues were approved for medical application. The same could be noted for acridone derivatives and origin of cycloferon. This preparation is rather unique and belongs to acridine’s set of compounds, well known in international pharmacology. First studies of acridone derivatives were initiated in the Institute of Experimental medicine at 70^th years in a frame of investigation anti-tumor antibiotic actinomycine D acricine - ring analogues/ All of these compounds were synthesized in Department of Dye chemistry Leningrad’s Institute of Technology. Most of those compounds elicited wide spectrum of biological activities. Key activity of those compounds was identified as a unique property: high capability to induce endogenous interferon synthesis. These compounds lacked capability to intercalate to the DNA molecules. Later several compounds were approved as strong an interferon inducers, for activation of a first line protection against viral infections